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Body, heart, thyroid gland and skeletal muscle weight changes in rats with altered thyroid status
Abstract
In the present paper we describe changes of anatomical parameters in inbred Lewis strain rats, namely their body weight, body weight gain per week, absolute and relative heart, thyroid gland and skeletal muscle weights, that are assumed to reflect experimentally altered thyroid status. The hyperthyroid state was induced by DL-thyroxine or Na 3,3',5-triiodo-L-thyronine, while methimazole was employed for inducing hypothyroidism. We have found that when compared to euthyroid rats, hypothyroidism resulted in a significantly lower body weight gain, absolute and relative heart weight and, in contrast, in a significant increase of absolute and relative thyroid gland weight. On the other hand, hyperthyroidism led to a significant increase of absolute and relative heart weight and to a significant reduction of absolute and relative thyroid gland weight. However, the body mass was not significantly altered in hyperthyroidism as compared with euthyroid rats. We conclude that our protocol leads to chronic hyper- or hypothyroidism as demonstrated by body, heart and thyroid gland weight changes. These anatomical data can thus be utilized as supplemental criteria for the assessment of the thyroid state of experimental rats.
... A significant shortening of the sinus node recovery time in the group with hyperthyroidism (EPS 3) indicates the enhancement of sinus node automatism due to thyroid hormones. Arrhythmia can be a consequence of the shortening of the refractory period as well as an increase in the dispersion of repolarisation observed in hypertrophied myocardium (2,3,16,17). ...
... Hyperthyroidism causes cardiac hypertrophy ( 2,4,(8)(9)(10)17), which was confirmed in the examined animals at the autopsy. The post-mortem examination showed concentric hypertrophy, typical of pressure-overload ( 6). ...
... In adult rats, the changes were present usually in the ventricles and the mechanism was different; the mass increased by means of hypertrophy. A considerable change in the thickness of the cardiac walls, as observed in many studies in different animal models ( 17), must result in the modification of the intraventricular conduction. The manifestation of the above-mentioned disturbances includes lengthening of the ventricular effective refractory period revealed in electrophysiological tests after 8-week administration of L-thyroxine. ...
To determine changes in physiological parameters of the myocardium in experimentally induced hyperthyreosis in an animal model, the occurrence and type of arrhythmias triggered during programmed electrical stimulation and changes in electrophysiological parameters of ventricular cardiomyocytes with hypertrophy due to hyperthyreosis were investigated. Hyperthyreosis was induced experimentally in five pigs, which were orally administered L-thyroxine at a dose of 20 μg/kg. Five untreated pigs served as the control. Programmed electrical stimulation was performed before administration of L-thyroxine (EPS 1), four (EPS 2) and eight (EPS 3) weeks after the onset of thyroxine administration, and four weeks after drug withdrawal (EPS 4). After the last stimulation, the animals were sacrificed and necropsied, with particular regard to heart autopsy. During the EPS 2, VERP was decreased in the group treated with the hormone (P<0.05). The mean values of AERP and AVNERP in the group were decreased as well. Atrial flutter and atrial fibrillation were induced during stimulation of the experimental group. In the other pigs of the experimental group, singular and paired ventricular extrasystolic were observed. In the EPS 3, AERP and AVNERP were statistically shorter in pigs with hyperthyreosis. A significant difference in Wenckebach CL between the control and experimental groups were observed. SNRT was shorter in the group with hyperthyreosis. In all pigs with hyperthyreosis, atrial fibrillation was induced. In one pig, non-sustained ventricular tachycardia was observed. During EPS 4, AERP remained shorter in group with hyperthyreosis. In two pigs of the group, atrial fibrillation was induced during pacing, and in two pigs, ventricular fibrillation was observed. The assessment of the heart's weight revealed a significant increase in its mass in pigs with hyperthyreosis. An increase in the thickness of the right and left ventricle free walls (P<0.01) and interventricular septum (P<0.01) was found in pigs with hyperthyreosis. At the same time, the inner diameter of the left ventricle was significantly smaller in this group (P<0.01) due to a concentric hypertrophy of the ventricle. In view of these findings, experimental hyperthyreosis caused shortening of refractory periods of different parts of the conducting system and enhanced susceptibility to supraventricular and ventricular arrhythmias, both spontaneous and induced during electrical stimulation. The mechanism of these arrhythmias can differ as a consequence of the hypertrophy of the left ventricle.
... Rozdíly mezi skupinami bez RPO a s RPO v dietě nebyly opět signifikantní. Výše uvedené anatomické parametry jsou v souladu s literaturou (Soukup et al., 2001). ...
... Vliv přídavků TH, respektive methimazolu k dietě, které byly pouţity k navození hyper-a hypothyroidního stavu, se výrazně projevily na změnách celkových koncentrací T 3 (Graf (Soukup et al., 2001). ...
In this thesis, we study morphological characteristics and functions of adipose tissue, especially regulation of the metabolism and endocrine functions of this tissue. Described is also the influence of long chain polyunsaturated fatty acids on the metabolic functions of adipose tissue and the involvement of this tissue in the metabolism of thyroid hormones (TH). The aim of the experimental part was to determine the influence of the administration of red palm oil in diet at different, experimentally adjusted non-physiologically high or low serum levels of TH on the specific enzyme activities of the key enzymes of TH metabolism, the iodothyronine deiodinases of types 1, 2 and 3 in various tissues of Wistar rats. We focused on the determination of deiodinases of types 1 and 3 in white and brown adipose tissue. We used radioimmunoanalysis for determination of TH serum levels and newly developed and adapted radiometric enzyme assays for determination of deiodinases activities. The obtained results of deiodinases determination, and their changes in dependence on changes of thyroid status of the rats, are in agreement with the expected ones and with those already achieved in our laboratory. The effects of RPO administration on the measured enzyme activities are not too marked. In general, RPO restrains undesirable effects of TH (i.e., too high or too low TH serum levels).
... When comparing MIRD and microdosimetric data, the 211 At activity in the thyroid gland was assumed to be homogeneously distributed within the follicle lumens, and 70% of the thyroid gland was assumed to consist of follicles in the microdosimetric calculations [29]. The cumulated activity equivalent to a mean absorbed dose to the thyroid of 1 Gy for the different species was calculated under the following assumptions: ϕ = 1, ∆ = 6.8 MeV and m is 3 mg for mouse, 30 mg for rat and 19 g for man [12,17,30,31]. ...
... When performing calculations for the different species, models were created based on the average thyroid follicle sizes. The mean weight of the thyroid gland for man is approximately 19 g (range 8 to 48 g) [30], for rat approximately 30 mg [31] and approximately 3 mg for mouse [12,17]. There is also a difference in follicle size between the species. ...
The alpha particle emitter 211At is proposed for therapy of metastatic tumour disease. 211At is accumulated in the thyroid gland in a similar way as iodine. Dosimetric models of 211At in the thyroid are needed for radiation protection assessments for 1) patients receiving 211At-labelled pharmaceuticals where 211At may be released in vivo and 2) personnel working with 211At. Before clinical trials, preclinical studies are usually made in mice and rats. The aims of this study were to develop thyroid models for mouse, rat and man, and to compare microdosimetric properties between the models.
A thyroid follicle model was constructed: a single layer of 6 to 10-μm thick follicle cells with centrally positioned 4 to 8 μm (diameter) spherical nuclei surrounded a 10 to 500 μm (diameter) spherical follicle lumen. Species-specific models were defined for mouse, rat and man. The source compartments for 211At were the follicle lumen, follicle cells and follicle cell nuclei. The target was the follicle cell nucleus. Simplified species-specific thyroid models were used to investigate the contribution from surrounding follicles. Monte Carlo simulations were performed using the general purpose radiation transport code MCNPX 2.6.0.
When 211At was homogeneously distributed within the follicle lumen, the mean specific energies per decay, 〈z〉, to the follicle cell nucleus were 2.0, 1.1 and 0.17 mGy for mouse, rat and man, respectively. Corresponding values for the single-hit mean specific energy per decay, 〈z1〉, were 1.3, 0.61 and 0.37 Gy. Assuming a homogeneous 211At concentration in the follicle lumen, <0.5%, 7%, and 45% of the emitted alpha particles were fully stopped within the follicle lumen for the respective models.
The results clearly show the influence of the follicle size, alpha particle range and 211At location within the thyroid follicle on the dosimetric parameters. Appropriate thyroid models are required for translation of dosimetric parameters between species.
... At present, we are studying the effects of innervation and thyroid hormone levels on fibre type composition and myosin heavy chain (MyHC) isoform expression in regenerating and adult slow soleus and fast extensor digitorum longus (EDL) muscles in rats with an experimentally-altered thyroid status (Zachařová et al., 1999;Ladecký et al., 2000;Soukup et al., 2001; for review see Soukup and Jirmanová, 2000). For this purpose, heterochronous isotransplantation was introduced (Jirmanová and Soukup, 1995), whereby the soleus or EDL muscle of 2-4-week-old rats of the Lewis strain are isografted either into the soleus or EDL muscle of the adult host inbred recipient of the same strain. ...
... The excised soleus and EDL muscles were immediately frozen in liquid nitrogen and treated as described previously (Soukup et al., 2001). To asses fibre type composition of the muscles (1, 2C, 2A and 2B), cryostat sections were processed for the histochemical assay to demonstrate myofibrillar adenosine triphosphatase (mATPase) activity after alkaline (pH 10.3) and acid (pH 4.5 and 4.3) preincubations (Dubowitz and Brooke, 1973). ...
SummaryWe have analysed the fibre type composition of soleus and extensor digitorum longus (EDL) muscles of normal female 4–6-month-old inbred Lewis rats. This rat strain is used in our ongoing study of the effects of thyroid hormone on myosin heavy chain (MyHC) isoform expression. On the basis of the mATPase reaction, soleus muscles contained 96.1 ± 2.9% of type 1 fibres supplemented by 2A fibres. EDL muscles contained type 1 (5.5 ± 1.0%), type 2A (18.8 ± 1.7%) and type 2B (75.7 ± 2.2%) fibres. Immunohistochemical analysis and SDS gel electrophoresis confirmed that most fibres in the soleus muscle expressed the type 1 (slow) MyHC isoform and that only a small proportion of fibres expressed the fast 2a MyHC isoform. Immunohistochemical analysis and SDS gel electrophoresis demonstrated that almost half of the 2B fibres of EDL muscles expressed the 2x/d MyHC isoform. In both muscle types, many fibres expressed more than one MyHC isoform. The content of slow fibres in the soleus muscle of female inbred Lewis rats was slightly higher than that reported for Wistar rats, but was considerably higher than that of Sprague-Dawley rats, whereas substantial differences were not found in the proportion of slow and fast fibre types in EDL muscles in these strains.
... However, a recent follow up study among Koreans could not find any significant effect of thyroidectomy on weight gain (Jin et al., 2022). Such observation has been consistently demonstrated in rodent studies (Soukup et al., 2001;Ahmed et al., 2012;Nida et al., 2016), accordingly, we did not find any significant effect of thyroidectomy on the weight gained by the male Wistar rats in this study. The discrepancy in the animal studies and the earlier human studies was adduced to the difference in the mechanism by which energy is dissipated. ...
Derailed glucose homeostasis is well documented in hypothyroidism and studies have found Ocimum gratissimum leaf extract (OG) to be beneficial in other conditions such as diabetes mellitus and metabolic syndrome characterized by imbalance glucose homeostasis. There is however dearth of information on the effect of OG in hypothyroid condition. This study therefore investigated the effect of OG on glucose metabolism in thyroidectomy-induced hypothyroid male Wistar rats. Thirty-six male Wistar rats were randomly divided into six (6) groups (n=6) as 1 = control, 2 = control + OG, 3 =sham operated (Sham), 4 = Sham + OG, 5 = Thyroidectomized (Thyrd) and 6 = Thyrd + OG. Groups 1, 3 and 5 received 0.2 mL/kg of distilled water while 100 mg/kg of OG was administered to groups 2, 4 and 6 for 28 days post healing of the surgical site. Oral Glucose Tolerance Test was carried out, lactate level, lipid profile and markers of oxidative stress were assessed in the plasma while liver and muscle samples were obtained for the determination of glycogen content and hepatic hexokinase activities. Glucose intolerance was observed with increased AUC (18274 ± 442.55 mg.min/dL) in Group 5 and reversed in group 6 (15228±184.97 mg. min/dL) relative to control (14421±515.58 mg.min/dl). Hepatic hexokinase activity and plasma lactate level were significantly reduced in group 5. Muscle glycogen decreased in groups 2, 4, 5 and 6 while hepatic glycogen increased in groups 3, 5 and 6. Triglycerides and HDL decreased while LDL increased in group 5 and were reversed in group 6. Malondialdehyde level was increased, and catalase activity decreased in group 5 while they were reversed in group 6. Findings from this study suggest that OG may prevent suppression of hepatic hexokinase activity and thus promote glucose utilization in thyroidectomized male Wistar rats.
... Moreover, iodine deficiency can cause thyroid dysfunction. Low iodine intake can shift thyroid hormone utilization from T4 to the more biologically active T3 by upregulating peripheral type II deiodinase and increasing thyroid secretion of T3 [21,22]. ...
Iodine is an essential trace element for humans and the main raw material for thyroid hormone synthesis. However, the association between iodine nutritional status and adverse pregnancy outcomes in different regions remains controversial. This single-center cohort study was focused on the association between iodine nutritional status and adverse pregnancy outcomes in Beijing, China. We enrolled 726 pregnant women who were registered at the Peking University International Hospital between February 2017 and December 2019. To analyze the association between iodine nutritional status variations and adverse pregnancy outcomes, this study cohort included 390 (53.72%) participants with iodine deficiency, 206 (28.37%) with an adequate iodine level, 103 (14.19%) with a more than adequate iodine level, and 27 (3.72%) with iodine excess, according to the urinary iodine (UI) status of pregnant women. After adjusting for age, body mass index, parity, and history of spontaneous abortion, we identified iodine deficiency as a risk factor for anti-thyroid peroxidase antibody (TPOAb) positivity [odds ratio (OR), 3.646; 95% confidence interval (95% CI), 1.658–8.017], anti-thyroglobulin antibody (TGAb) positivity (OR, 3.109; 95% CI, 1.465–6.599), and thyroid autoimmunity (OR, 2.885; 95% CI, 1.539–5.407). There was a non-linear relationship between UI and the concentrations of TPOAb and TGAb ( P non-linear < 0.05). Iodine deficiency during the first trimester is a risk factor for thyroid autoantibody positivity. The relationship between UI and the concentrations of TPOAb and TGAb follows a nearly U-shaped curve. Thus, physicians should critically consider the iodine nutritional status of pregnant women during the first trimester. Clinical Trials.gov Identifier: NCT02966405
... An increase in thyroid weight was noted in the group that was administered ZnONPs (Table 4). The weight increase of the thyroid gland may be attributed to the induction of hypothyroidism and compensatory hypertrophy (Soukup et al. 2001). Histological examination of the thyroid glands of control and vehicle groups ( Figure 2) showed normal organization with different sized thyroid follicles that were filled with vacuolated acidophilic homogenous colloid. ...
Zinc oxide nanoparticles are incorporated into cosmetics and sunscreens, and are widely used in biomedical applications and food industry. The increasing use of zinc oxide nanoparticles raises concern about their safety. This aim of the study was to assess the effects of zinc oxide nanoparticles on oxidative and genotoxic parameters in thyroid gland and liver of adult albino rats. Rats were divided into three groups; control, vehicle, and zinc oxide nanoparticles (200 mg/kg) and where subjected to treatment for 30 days. Oxidative stress parameters and genotoxicity was determined. Histopathological examination of both organs was undertaken. A significant reduction in triiodothyronine, thyroxine, and thyroid-stimulating hormone was noted, whereas aspartate aminotransferase and alanine aminotransferase levels were significantly elevated. Increased malondialdehyde and decreased reduced glutathione levels were indicative of oxidative stress response in both organs. Additionally, elevated serum 8-hydroxydeoxyguanosine was noted which was supported by results of the comet assay. Histopathological examination revealed alterations in thyroid gland and liver. Sub-chronic exposure resulted in oxidative stress mediated toxicity and genetic perturbations in both organs. Caution is warranted with repeated usage of products containing zinc oxide nanoparticles.
... rats with PTU-induced hypothyroidism support our results. In addition, Soukup et al. (2001) stated that the body weight gain per week was very low during the experimental period in hypothyroid rats and that their body growth was practically arrested. In the light of this information, the body weight reduction of the rats in the HT group may be related to the decrease in feed intake and basal metabolism. ...
In our study, the effect of essential oil obtained from Nigella sativa L. (NSE) on thyroid hormones and antioxidant balance in hypothyroidism (HT) and hyperthyroidism (HP) models induced by propylthiouracil(PTU) and L-thyroxine(LT4), respectively, in rats were investigated for 4 weeks. NSE was administered by gastric gavage at a dose of 200 mg/kg body weight. In this study, 48 male Wistar albino rats with an average weight of 180–290 g and age 5–6 months were divided into eight groups, as follows: groups with HT, (1) control, (2) HT, (3) NSE, and (4) HT + NSE; groups with HP, (1) control, (2) HP, (3), and NSE (4) HP + NSE. As a result, we found that NSE administration increased total triiodothyronine (TT3) and decreased nitric oxide in HT + NSE. Besides, it decreased TT3 in HP + NSE and increased total antioxidant capacity. Our findings suggest that NSE may have beneficial effects on thyroid gland abnormalities owing to its antioxidant properties.
Practical applications
Essential oils derived from Nigella sativa L. seed contain many bioactive substances such as thymoquinone and cymene. This paper emphasizes the effect of NSE on thyroid hormone abnormalities and negative oxidative state that occurs in HT and HP models. The present study provides evidence of a positive effect of NSE particularly on TT3 levels in the HT and HP models. It can therefore be assumed that NSE could be used as a supportive natural alternative source to improve thyroid hormone levels and relieve increased oxidative stress.
... In line with our result, regardless of the method for induction of hypothyroidism, lower body weight, food intake, and water consumption have been reported in hypothyroid rats [17][18][19][20][21][22][23][24][25]. Effects of hyperthyroidism on body weight, food intake, and water consumption are however, controversial and decreased [17,18], increased [26], or even no changes [27,28] have been reported. In general, thyroid hormones increase food intake by increasing appetite [29][30][31] and decrease body weight by increasing metabolism [29,32]. ...
Background and Objective
All three isoforms of nitric oxide (NO) synthase (NOS) are targets for thyroid hormones in cardiovascular system. The aim of this study was to assess effects of hypoand hyperthyroidism on inducible (iNOS), endothelial (eNOS), and neural (nNOS) NOS levels in aorta and heart tissues of male rats.
Methods
Rats were divided into control, hypothyroid, and hyperthyroid groups; hypo- and hyperthyroidism were induced by adding propylthiouracil (500 mg/L) and L-thyroxine (12 mg/L) to drinking water for a period of 21 days, respectively. At day 21, systolic blood pressure, heart rate, left ventricular developed pressure (LVDP), peak rate of positive and negative (±dp/dt) changes in left ventricular pressure as well as NO metabolites (NOx) and iNOS, eNOS, and nNOS protein levels in aorta and heart were measured.
Results
Compared to controls, LVDP and ±dp/dt were lower in both hypo- and hyperthyroid rats. Compared to controls, heart rate and systolic blood pressure were lower in hypothyroid and higher in hyperthyroid rats. NOx levels in the heart of hypothyroid rats were lower (53%) whereas in the heart and aorta of hyperthyroid rats were higher (56% and 40%) than controls. Compared to controls, hypothyroid rats had lower levels of eNOS, iNOS, and nNOS in aorta (16%, 34%, and 15%, respectively) and lower iNOS and higher nNOS in heart tissue (27% and 46%). In hyperthyroid rats, eNOS levels were lower (54% and 30%) and iNOS were higher (63%, and 35%) in the aorta and heart while nNOS was lower in the aorta (18%).
Conclusion
Hypothyroidism increased while hyperthyroidism decreased ratio of eNOS/iNOS in aorta and heart; these changes of NOS levels were associated with impaired cardiovascular function.
... The gland is bilobulted structure connected centrally by an isthmus, resembling a butterfly shape (Sood et al., 2011). Because of its high vascularity due to an arteriole plexus suppllied by the superior and inferior thyroid arteries, so the colour of thyroid gland is ranged from dark red to brownish (Soukup et al., 2001). There are four structures are embedded in the posterior surface of the thyroid gland which called the parathyroid glands, each one is ranged from 3-8 mm in length, and 2-5 mm in width (Brander et al., 1991). ...
Abstract
Diabetes mellitus (DM) is a group of aetiologically different metabolic defects characterized by hyperglycemia resulting from defect in insulin secretion as well as insulin action or both. Occasionally other endocrine disorders like abnormal thyroid hormone level are found in diabetes. Diabetes and thyroid disorders have been shown to mutually influence each other and associations between both conditions have long been reported. This study has been done at The National Diabetes Center of AL-Mustansiria University from October 2017 to April 2018. Ninety men with age ranged from (35-65) years were involved in this study. Divided into four groups ; G1(15 healthy control), G2 (15 patients with type 2 DM), G3 (30 patients with type 2 DM and hypothyroidism), and G4 (30 patients with type 2 DM and hyperthyroidism). Blood samples were collected from each individual via vein puncture to assess fasting blood glucose (FBG), glycated hemoglobin (HbA1c), Insulin, Glucagon, and levels of thyroid hormones: thyroid stimulating hormone (TSH), Thyroxine (T4), and Triiodothyronine (T3). The result showed highly significant (p < 0.01) increase in the level of TSH in diabetic with hypothyroidism group, and highly significant (p < 0.01) decrease in level of TSH in diabetic with hyperthyroidism group when compared to diabetic and control groups. And there was no significant difference between diabetic group and control group. Level of T4 and T3 showed highly significant (p < 0.01) increase in diabetic with hyperthyroidism group and highly significant (p < 0.01) decrease in diabetic with hypothyroidism group when compared to the diabetic group and healthy control group. Furthermore, there was no significant difference between diabetic group and healthy control group. The result showed highly significant (p < 0.01) increase in the level of insulin, insulin resistance, and glucagon in diabetic with hyperthyroidism group when compared to diabetic
II
with hypothyroidism group, diabetic group, and healthy control group. Also there was highly significant (p < 0.01) increase in the level of insulin, insulin resistance, and glucagon in diabetic with hypothyroidism group and diabetic group when compared to the healthy control group. while the results showed no significant difference increase in the level of insulin, insulin resistance, and glucagon between diabetic with hypothyroidism group and diabetic group. The result showed highly significant (p < 0.01) increase in the levels of fasting blood glucose (FBG), and HbA1c in diabetic with hyperthyroidism group, diabetic with hypothyroidism group, and diabetic group when compared to the healthy control group.
... In the present study, assessment of thyroid functional status by measurement of serum thyroid hormone revealed that the observed increase in thyroid weight of animals exposed to increased doses of AgNPs for subchronic and chronic durations displayed hypofunctining of thyroid gland, moreover microscopic examination of thyroid tissue showed dose and time dependent of diffused hypertrophy ,hyperplasia of follicular cells, along with increased number of follicles, depletion of colloid material and reduced lumen size in comparison to control animals. These findings consistent with previous data reported by (Soukup et al., 2001) , who found a direct significant increase in thyroid gland weight in response to hypothyroidism and thyroid gland hypertrophy. In this path, various experimental animal studies concerned with the effects of heavy metals on the thyroid glands. ...
Time and dose depedent alteration in thyroid function manifested by
considerable increase in thyroid weight, with significant reduction in
serum levels of thyroxin (T4), that supported by histological changes of
thyroid tissue. On other hand, both (T3) and (TSH) non significantly
affected.
Time dependent disturbances in Estrogen levels, which initially
increased after (10)days of treatment, followed by significant reduction
after (30)day of treatment, that associated with marked alterations in
normal histology of ovarian tissues. Also, the levels of both LH and
prolactin displayed significant reduction after (30)day of treatment with
high dose (50mg/Kg) of AgNPs.
In addition, a considerable increase in weight of mammary gland,
which showed histological changes as deplesion in the numbers of
acini and secretory ducts, with marked increase in the area of adipose
tissues of mammary gland. However, other hormones as progesterone
and FSH non significantly affected by AgNPs.
In summary the AgNPs cause hypothyroidism (disfunction of thyroid
gland) associated with reproductive disfunction.
... Result showed that ZnO NPs effects on thyroid weights as it was demonstrated in figure(2), . Results of the present study about the elevation in thyroid weight is in agreement with a previous study by [26] who reported significant increase in thyroid weight in response to hypothyroidism and hypertrophy in thyroid gland. [27] who showed that thyroid weight in hypothyroidism rats was significant enlarged. ...
Engineered nanoparticles application in food, such as those used as delivery systems for colors, preservatives flavors, nutrients, and food packaging .Zinc oxide nanoparticles are used in various application include dyes, paints, pigments, medical diagnosis, sunscreens, cosmetics .The present study aims to investigate the side effects of ZnO NPs on the weight of body and organ in male rats .For this study 54 Spargue-Dawley albino adult male rats were classified into three main groups each of 18 rats treated for a particular duration (7,14,28) days respectively. Each group was subdivided into three subgroups each of six rats treated as follows ; group (1) serve as normal control ,group (2,3) intra-peritoneal treated with ZnO NPs (30,60) mg/kg respectively, body weight of all rats was measured before and after the experiment, then rats were dissected at the end of each experiment and the weights of thyroid, liver, testes, and kidneys were measured. Result showed high significant increase (p<0.01) in thyroid gland ,body and kidney weights in all different doses (30,60)mg/kg at durations 7,14 and 28 days ,while the weight of liver and testes showed high significant decreament (p<0.01) at all doses(30,60)mg/kg for all duration of time(7,14 ,28) days.
... The wide applications of AgNPs in nonmedical and pharmacological products directed the search toward safety guidelines and possible toxicity mediated by the release of biologically active Ag+ into the human body [16]. In this concern, the results of the present study agreed with the data reported by Soukup et al., where they found a significant increase of thyroid gland weight in animals with hypothyroidism due to thyroid gland hypertrophy [17]. The function of the thyroid gland is often maintained by a negative feedback mechanism, which involves the interplay between the hypothalamus (through the TRH release) and the TSH released from the pituitary gland. ...
Objective: Due to their unique properties, silver nanoparticles (AgNPs) gained a broad utilization in nano-based industries and medicine, which may expose human to increased levels of NPs. However, little is known about their potential harmful effects on endocrine physiology. Hence, this study aimed to investigate the potential dose- and time-dependent outcomes of AgNPs on serum levels of thyroid hormones and thyroid gland histology in female rats.Methods: A total of 60 female rats were divided into three groups (each of 20 animals), treated with AgNPs for (10, 20, and 30) days. Within each treatment period, animals were assigned into four subgroups each of five rats; control treated with vehicle and the others treated with 12.5, 25, and 50 mg/kg of AgNPs, respectively, by intraperitoneal injection. At the end of treatments, all rats were sacrificed; blood samples were obtained and analyzed for serum levels of T3, T4, and thyroid-stimulating hormone (TSH). Thyroid gland was removed and weighed then kept in buffered formalin solution for microscopic examination.Results: The data showed a significant increase in the weight of the thyroid gland after 20 and 30 days of the treatment with 50 mg/kg of AgNPs, while the 25 mg/kg dose of AgNps resulted in significant increase only after 30 days. Serum levels of T3 and TSH were nonsignificantly altered by AgNPs in all the treatment groups. Thyroxin levels (T4) were significantly decreased after long-term exposure. Histological specimens of AgNPs treated group showed disturbance of the normal architecture of the thyroid tissue with degeneration of thyroid follicles and desquamated luminal cells.Conclusion: The results of the current study suggested the possible disrupting potential of long-term exposure to high level of AgNPs on thyroid gland function and histology in female rats.
... The present study revealed a decrease in body weight and body weight gain in hyperthyroidism male rabbits compared control. This result agrees with Soukup et al. (2001) the likelihood of weight loss occurring was related to the severity of the overactive thyroid. Thus, if the thyroid is extremely overactive, the individual's BMR increases which leads to increased caloric requirements to maintain that weight. ...
... The present study revealed a decrease in body weight and body weight gain in hyperthyroidism male rabbits compared control. This result agrees with Soukup et al. (2001) the likelihood of weight loss occurring was related to the severity of the overactive thyroid. Thus, if the thyroid is extremely overactive, the individual's BMR increases which leads to increased caloric requirements to maintain that weight. ...
Oil seeds of Linum usitatissimum are exhibited numerous interesting pharmacologic activities, very potent antioxidant. Our study is to investigate the therapeutic effect of oil of seeds Linum usitatissimum against levothyroxin sodium –induced hyperthyroidism in female rabbits. The rabbit was used as a model to study the effects of hyperthyroidism induced with supra-physiologic doses of L-thyroxin sodium (L-T 4). Endocrine aspects of the thyroid in the pituitary-thyroidaxis have been studied extensively, but few controlled studies have been conducted on females with hyperthyroidism. Thirty two female rabbits were divided randomly into four groups. Group 1: Rabbits received orally administration of normal saline (3 ml) for 30 days (as served control group). Group 2: Rabbits received orally administration of L-thyroxin sodium at dose 50 µg/kg B.W/day dissolve in 3 ml normal saline for 10 days for induced hyperthyroidism. Group 3: Rabbits received orally administration of L-thyroxin sodium at dose 50 µg/kg B.W/day dissolve in 3 ml normal saline for 10 days for induced hyperthyroidism and treated with oil of Linum usitatissimum (1 ml/kg B.W) for 20 days. Group 4: Rabbits received orally administration of oil of Linum usitatissimum (1 ml/kg/B.W) only for 30 days. The experimental results revealed that hyperthyroid rabbits had significant decrease (P<0.05) body weight and body weight gain, TSH, haematological parameters such as RBCs, Hb, PCV, WBC, Neutrophils and total protein levels while significant increase (P<0.05) in serum level of T3, T4, Basophils %, Eosinophils, Monocyte %, lipid profile, glucose concentration and urea. Histological sections showed that the changes of thyroid, heart, liver and kidney was moderately depressed in hyperthyroid female rabbits. Oil of Linum usitatissimum treatment suppresses the hyperthyroidism-induced oxidative damage. These results suggest that experiment is accompanied with increased oxidative aggressions. A therapeutic effect of oil of Linum usitatissimum on oxidative stress in hyperthyroidism female rabbits induced by excessive administration of thyroid hormones were detected and for the first time antithyroid activity were observed. Article History
... The results of the present study shows that the administration of levothyroxine sodium (L-T4) increased the serum total T3 (TT3) and total T4(TT4) levels as compared with control group [ The reference range of total T3 (0.8-1.8ng/ml and total T4 (6.4-8.3 µg/dl) (Jones 1975)] the increase in thyroid hormones level may be due to L-T4 absorbed well by gut, thus increasing level of thyroxine (T4) in circulation, which is then converted into triiodothyronine (T3) by iodothyronine deiodinases (Duntas 2006). The same observation was found in other studies Panda and Kar (2003) and Soukup et al., (2001) observed a high concentration of thyroid hormones after treatment with L-T4. (Kossler et al., 1987) induced hyperthyroidism state in rat by thyroxine sodium as well. ...
... The results of the present study shows that the administration of levothyroxine sodium (L-T4) increased the serum total T3 (TT3) and total T4(TT4) levels as compared with control group [ The reference range of total T3 (0.8-1.8ng/ml and total T4 (6.4-8.3 µg/dl) (Jones 1975)] the increase in thyroid hormones level may be due to L-T4 absorbed well by gut, thus increasing level of thyroxine (T4) in circulation, which is then converted into triiodothyronine (T3) by iodothyronine deiodinases (Duntas 2006). The same observation was found in other studies Panda and Kar (2003) and Soukup et al., (2001) observed a high concentration of thyroid hormones after treatment with L-T4. (Kossler et al., 1987) induced hyperthyroidism state in rat by thyroxine sodium as well. ...
... The results of the present study shows that the administration of levothyroxine sodium (L-T4) increased the serum total T3 (TT3) and total T4(TT4) levels as compared with control group [ The reference range of total T3 (0.8-1.8ng/ml and total T4 (6.4-8.3 µg/dl) (Jones 1975)] the increase in thyroid hormones level may be due to L-T4 absorbed well by gut, thus increasing level of thyroxine (T4) in circulation, which is then converted into triiodothyronine (T3) by iodothyronine deiodinases (Duntas 2006). The same observation was found in other studies Panda and Kar (2003) and Soukup et al., (2001) observed a high concentration of thyroid hormones after treatment with L-T4. (Kossler et al., 1987) induced hyperthyroidism state in rat by thyroxine sodium as well. ...
This study was undertaken to extract catechins from green tea leaves. It is to show the curative effect of green tea catechins after a short term daily oral administration for 8 days (200 mg̸ kg b.w) on serum level of thyroid hormones and thyroid-stimulating hormone in hyperthyroid rabbits induced by levothyroxine sodium (L-T4). Rabbits were divided into 4 groups, 6 rabbits in each group. Group 1 animals received only 3 ml normal saline orally as control group , group 2 was treated with (L-T4) 0.3 mg̸ kg b .w as hyperthyroidic. The 3rd group hyperthyroidic rabbits were post-treated with green tea catechins extract (200 mg̸ k g b.w) while the 4th group hyperthyroidic rabbits were post-treated with carbimazole (5 mg ̸ kg b.w). The results indicated high significantly increased (p< 0.001) in serum level of total triiodothyronine (TT3), total thyroxine (TT4) and high significantly stimulating hormone in hyperthyroid rabbits.
... The EU rats were age-matched littermates of the experimental animals. The effect of the procedure was assessed by measuring biochemical and anatomical parameters that are known to be influenced by thyroid hormone level alterations (Soukup et al. 2001;Rauchova et al. 2011;Kopecká et al. 2014). One-half of the animals were fed daily by RPO (100 µL/100 g body weight) one week before and until the end of experiment. ...
We aimed to study the impact of altered thyroid status on myocardial expression of electrical coupling protein connexin-43 (Cx43), the susceptibility of rats to ventricular fibrillation (VF) and the effects of antioxidant-rich red palm oil (RPO). Adult male and female euthyroid, hyperthyroid (treated with T3/T4), hypothyroid (treated with methimazole) Wistar rats supplemented or not with RPO for 6 weeks were used. Function of isolated perfused heart and VF threshold were determined. Left ventricular tissue was used for assessment of mRNA and protein levels of Cx43, its phosphorylated forms and topology. Protein kinase C signaling (PKC) and gene transcripts of some proteins related to cardiac arrhythmias were assessed. Hyperthyroid state resulted in decrease of total and phosphorylated forms of Cx43 and suppression of PKC-ε expression in males and females, decrease of Cx43 mRNA in females, decrease of VF threshold and increase of functional parameters in male rat hearts. In contrast, hypothyroid status resulted in the increase of total and phosphorylated forms of Cx43, enhancement PKC-ε expression in males and females, increase of Cx43 mRNA in females, increase of VF threshold and decrease of functional parameters in male rat hearts. Function of the heart was partially normalized by RPO intake, which also enhanced myocardial Cx43 and PKC-ε expression as well as increased VF threshold in hyperthyroid male rats. We conclude that there is an inverse relationship between myocardial expression of Cx43, including its functional phosphorylated forms, and susceptibility of male rat hearts to VF in condition of altered thyroid status. RPO intake partly ameliorated adverse changes caused by excess of thyroid hormones.
... The average weight of the euthyroid (normal thyroid) gland in mice, rats and man are approximately 3 mg [14], 30 mg [15] and 19 g [16], respectively. The size of the thyroid gland also varies depending on sex, age, diet, thyroid disorders, and during pregnancy [17]. ...
The radiohalogens 123I, 124I, 125I, 131I, and 211At are routinely used or proposed for diagnostic and therapeutic purposes. The different characteristics and application areas of these radioiodine isotopes, together with the possibility to bind them to the same carrier molecule, give many advantages, for example, by enabling relevant biodistribution and dosimetric studies important for dose-planning before radionuclide therapy. 211At, with its relatively long half-life, stable daughter nuclide, and production and labelling possibilities is considered as one of the most attractive alpha particle emitters in radionuclide therapy. With growing use of radiohalogens in both preclinical and clinical studies there is a need for accurate species-specific dosimetric models both for tumours and normal tissues. The thyroid gland has shown a high uptake of radioiodide and free 211At and is, therefore, considered as an organ at risk. It is thus critical to be able to accurately calculate the absorbed dose in the thyroid. Accurate dosimetry is also important for radiation protection purposes for personnel handling radiohalogens and for populations exposed to radioiodine, e.g., at a nuclear accident. The MIRD formalism is commonly used for calculating the mean absorbed dose, assuming a homogeneous distribution of the radionuclide within the thyroid gland. Several studies have shown heterogeneous distribution of radioiodine and 211At within the thyroid gland. In this work, geometrical models were developed for different species: man, rat and mouse. Microdosimetric calculations for heterogeneous distributions of the different radiohalogens in these thyroid models were performed using MCNPX Monte Carlo code and recent nuclear decay data. The results showed large differences in mean absorbed dose compared with MIRD formalism. The heterogeneity in absorbed dose within the thyroid depends on the type and energy of the emitted particles. For example, 131I emits high-energy beta particles with range up to 2 mm in tissue, where the absorbed dose distribution within the thyroid is less dependent on the radionuclide distribution. On the other hand, for 211At emitting alpha particles with short range in tissue (48-70 μm), and for 125I emitting Auger electrons with very short range in tissue (from a fraction of a nm up to 20 μm), the absorbed dose distribution will be more dependent on the radiohalogen distribution. The results also demonstrate the importance of using species-specific models for dosimetric calculations for thyroid and other heterogeneous tissues, enabling dosimetric translations between different species.
... Absolute and relative masses of thyroid gland were unchanged after both treatments, while stereological analysis showed no differences in the relative abundance of main thyroid tissue compartments (parenchyma vs. interstitium) between control and experimental groups. These results are in disagreement with the data reported previously by Soukup et al. (2001) who found markedly atrophied thyroids in rats treated with high doses of thyroid hormones. However, considerably shorter duration of our experiment (5 days vs. 6 month) offers a good explanation for the absence of changes in mentioned parameters. ...
The aim of the present study was to investigate histological alterations of rat thyroid gland after short-term treatment with supraphysiological doses of thyroid hormones. Rats from experimental groups were treated with triiodothyronine (T3) or thyroxine (T4) during five days. In both treated groups, thyrocytes height was reduced and follicular lumens were distended. Progressive involutive changes of thyroid parenchyma were apparent, including follicular remodelling (fusion) and death of the thyrocytes. Morphological changes confirmed by quantitative analysis were more pronounced in T4-treated group. Our results demonstrate that thyrotoxicosis, whether induced by T3 or T4, leads to different grades of thyroid tissue injury, including some irreversible damages. These changes might be explained at least in part by the lack of trophic and cytoprotective effects of thyroid stimulating hormone. Since period required for morphophysiological recovery may be unpredictable, findings presented here should be taken into consideration in cases where the thyroid hormones are used as a treatment for thyroid and non-thyroid related conditions.
... increased body weight. However, these findings are in agreement with previously reported data on rats [125,126,127,128,129,130,131]; those studies showed that, in hypothyroid rats, the body weight gain per week was very low (approximately one-sixth as high as the weight gain of euthyroid rats) and the body growth was strongly restricted. Additionally, the hypothyroid state was found to increase the serum leptin level; the "satiety hormone" leptin suppresses food intake in hypothyroid rats and may reduce the level of metabolism and body growth gain [132,133,134]. ...
The cardiovascular effects of mild and overt thyroid disease include a vast array of pathological changes. As well, thyroid replacement therapy has been suggested for preserving cardiac function. However, the influence of thyroid hormones on cardiac remodeling has not been thoroughly investigated at the molecular and cellular levels. The purpose of this paper is to study the effect of hypothyroidism and thyroid replacement therapy on cardiac alterations. Thirty Wistar rats were divided into 2 groups: a control (n = 10) group and a group treated with 6-propyl-2-thiouracil (PTU) (n = 20) to induce hypothyroidism. Ten of the 20 rats in the PTU group were then treated with L-thyroxine to quickly re-establish euthyroidism. The serum levels of inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL6) and pro-fibrotic transforming growth factor beta 1 (TGF-β1), were significantly increased in hypothyroid rats; elevations in cardiac stress markers, brain natriuretic peptide (BNP) and cardiac troponin T (cTnT) were also noted. The expressions of cardiac remodeling genes were induced in hypothyroid rats in parallel with the development of fibrosis, and a decline in cardiac function with chamber dilation was measured by echocardiography. Rapidly reversing the hypothyroidism and restoring the euthyroid state improved cardiac function with a decrease in the levels of cardiac remodeling markers. However, this change further increased the levels of inflammatory and fibrotic markers in the plasma and heart and led to myocardial cellular infiltration. In conclusion, we showed that hypothyroidism is related to cardiac function decline, fibrosis and inflammation; most importantly, the rapid correction of hypothyroidism led to cardiac injuries. Our results might offer new insights for the management of hypothyroidism-induced heart disease.
... Also, the relative heart weight was increased and that of thyroid gland reduced in HT status, while in HY rats, the thyroid glands hypertrophied significantly. These data confirmed the efficacy of the protocol used to induce chronic HT and HY status (Soukup et al. 2001Soukup et al. , 2012 Rauchova et al. 2011 Rauchova et al. , 2013). It is worth to note that our experiments were performed on female rats and it was shown that fiber type transition in response to T 3 increased levels can be different in males (Yu et al. 1999). ...
In this mini-review, we briefly present the data regarding the effect of extrinsic factors, i.e., innervation and thyroid hormones (TH) on myosin heavy chain genes and isoforms expression and consequently on muscle fiber type transitions. It has been well known that reduced neuromuscular activity, hyperthyroidism or mechanical unloading stimulate slow-to-fast fiber type transitions, while increased neuromuscular activity, hypothyroidism and higher mechanical loading result in fast to slow fiber type transitions. As there is a plethora of results on these topics, we focus mostly on data relevant to our experimental model of slow-to-fast muscle transformation following heterochronous intramuscular isotransplantation in rats with altered TH status.
... The EU rats were age-matched littermates of the HT and HY animals. The effect of our procedure was checked by measuring biochemical and anatomical parameters that are known to be influenced by TH level alterations ( Soukup et al. 2001, Rauchová et al. 2004, Pavelka 2014). ...
Recently we have established that slow soleus (SOL) and fast extensor digitorum longus (EDL) muscles of euthyroid (EU) Lewis rats posses the same proportions between their four myosin heavy chain (MyHC) mRNAs, protein isoforms and fiber types as determined by real time RT-PCR, SDS-PAGE and 2-D stereological fiber type analysis, respectively. In the present paper we investigated if these proportions are maintained in adult Lewis rats with hyperthyroid (HT) and hypothyroid (HY) status. Although HT and HY states change MyHC isoform expression, results from all three methods showed that proportion between MyHC mRNA-1, -2a, -2x/d, -2b, protein isoforms MyHC-1, -2a, -2x/d, -2b and to lesser extent also fiber types 1, 2A, 2X/D, 2B were preserved in both SOL and EDL muscles. Furthermore, in the SOL muscle mRNA expression of slow MyHC-1 remained up to three orders higher compared to fast MyHC transcripts, which explains the predominance of MyHC-1 isoform and fiber type 1 even in HT rats. Although HT status led in the SOL to increased expression of MyHC-2a mRNA, MyHC-2a isoform and 2A fibers, it preserved extremely low expression of MyHC-2x and -2b mRNA and protein isoforms, which explains the absence of pure 2X/D and 2B fibers. HY status, on the other hand, almost completely abolished expression of all three fast MyHC mRNAs, MyHC protein isoforms and fast fiber types in the SOL muscle. Our data present evidence that a correlation between mRNA, protein content and fiber type composition found in EU status is also preserved in HT and HY rats.
... 1 3 1995), whereby slow SOL or fast EDL muscles from young rats are intramuscularly transplanted into the fast EDL or slow SOL host muscle of inbred adult recipients of the same strain with different TH status (Zacharova et al. 1999(Zacharova et al. , 2005Soukup and Novotova 2000;Jirmanova and Soukup 2001;Soukup et al. 2001Soukup et al. , 2009Soukup et al. , 2012). This approach makes it possible to analyze the contribution of genetic factors given by the fast or slow muscle cell lineage and the fast or slow impulse frequency of the host reinnervating axons and of the experimentally altered levels of TH in a single experimental model. ...
We studied the effect of regeneration, altered innervation and thyroid hormone (TH) levels on fiber type transitions in slow soleus (SOL) muscles grafted (GRAFT) into host extensor digitorum longus (EDLh) muscles of euthyroid (EU), hyperthyroid (HT) and hypothyroid (HY) Lewis strain rats. SOL muscles were excised from 3-week to 4-week-old inbred Lewis rats and intramuscularly transplanted into EDLh muscles of 2-month-old female rats of the same strain. The proportions of type 1, 2A, 2X and 2B fibers of GRAFT were determined by immunohistochemistry and compared with those of EDLh muscle and EDL and SOL muscles of the unoperated contralateral hind limb. After an average regeneration period of 6-7 months and after being reinnervated by the "fast" peroneal nerve of EDLh muscle, GRAFT was transformed into a fast muscle. However, the extent of GRAFT transformation varied with different TH states. In the EU rats, GRAFT contained about 95 % of fast fibers, among which type 2X and 2B fibers predominated (about 75 %). The transition toward fast muscle phenotype was more pronounced in HT status, where the fastest type 2B fibers predominated. On the contrary, in HY status, the slow to fast transformation was less pronounced, as GRAFT contained less type 2B and 2X but more type 2A and 1 fibers. We conclude that the type of innervation is the crucial factor for the slow to fast fiber type transitions in GRAFT, but the extent of muscle transformation is further modulated by altered TH status.
... The euthyroid (EU) rats were age-matched littermates of the TH and HY animals. The effect of the procedure was checked by measuring total T 3 (tT 3 ) and total T 4 (tT 4 ) levels by a radioimmunoassay using commercial RIA kits (Immunotech-Beckman Coulter Co., Prague, Czech Republic) for human and rat sera (Pavelka 2002, Fig. 1A), by measurement of GPDH activity ( Rauchová et al. 2004Rauchová et al. , 2011) and of heart and thyroid gland weights ( Soukup et al. 2001, Fig. 1B,C); all these parameters are known to be affected by thyroid hormone level alterations and their measurements clearly demonstrated efficiency of our procedure. ...
We have investigated expression of skeletal calsequestrin (CSQ1) and fiber type composition in normal and regenerated fast and slow skeletal muscles and in the left heart ventricles of euthyroid (EU), hypothyroid (HY) and hyperthyroid (TH) adult inbred Lewis strain rats. The CSQ1 level was determined by SDS-PAGE followed by Western blot analysis. CSQ1 gene expression was assessed using reverse transcription and subsequent real time polymerase chain reaction. Muscle regeneration was achieved by intramuscular grafting of either soleus or extensor digitorum longus (EDL) from 3- to 4-week-old rats to either EDL or soleus muscle of 2-month-old rats. The fiber type composition was assessed by a stereological method applied to stained muscle cross sections. We found that the protein and mRNA levels for CSQ1 were highest in the EDL muscle, the relative CSQ1 protein levels in the soleus muscle were two times lower and the transcript levels more than 5 times lower compared to the EDL. In the left heart ventricle, protein isoform and CSQ1 transcript were also present, although at protein level, CSQ1 was hardly detectable. TH status increased and HY status decreased the expression of CSQ1 in the EDL, but its relative levels in the soleus and in the heart did not change. The regenerated soleus transplanted into EDL, as well as EDL transplanted into soleus exhibited protein and mRNA levels of CSQ1 corresponding to the host muscle and not to the graft source. TH status increased the percentages of the fastest 2X/D and 2B fibers at the expense of slow type 1 and fast 2A fibers in the EDL and that of fast 2A fibers in the soleus at the expense of slow type 1 fibers. HY status led to converse fiber type changes. We suggest that the observed changes in CSQ1 levels in TH and HY compared to EU rats can be related to fiber type changes caused by alteration of the thyroid status rather than to the direct effect of thyroid hormones on CSQ1 gene expression.
... Abundant researches conducted on mammals and chickens showed that TH had critical role in skeletal muscle development (Rooyackers and Nair, 1997;Schmid et al., 2003). Hypothyroidism signiWcantly decreases the body and muscle weight in rats (Soukup et al., 2001). However, information about TH actions on body mass accretion and muscle deposition in Wsh is limited. ...
The role of thyroid hormone (TH) and its receptors (TRs) in the regulation of body growth and muscle accretion is well established in mammals and birds, whereas the involvement of THs and TRs in fish growth, especially during the muscle accretion period of juvenile-adult transition, is unknown. This study describes the cloning of the partial cDNA sequences of TRα and TRβ in large yellow croaker, Pseudosciaena crocea (Richardson) and the patterns of TRα and TRβ mRNA expression in liver and muscle of 1- and 2-year-old large yellow croaker, associated with changes in body mass and muscle characteristics. Two TRα isoforms (TRα1, TRα2) and TRβ were identified in large yellow croaker. The deduced amino acid sequences showed high homology to the TRs of human and other teleosts. Hepatic TRβ mRNA expression was markedly lower in 2-year-old large yellow croaker compared with the 1-year-old, while no significant age difference was observed for hepatic TRα mRNA expression. Muscle expression of TRα mRNA was significantly higher in 2-year-old large yellow croaker, whereas TRβ exhibited no significant age difference. Meanwhile, serum concentration of T4 was significantly decreased in 2-year-old large yellow croaker, but no change was observed for T3. The body mass, fork length and body height of 2-year-old large yellow croaker were 4.7, 1.6 and 1.7 times greater, respectively compared with that of 1-year-old. Average diameters of skeletal muscle in 2-year-old large yellow croaker were remarkably larger than that in 1-year-old with no significant difference in muscle crude fat content. The down-regulation of hepatic TRβ expression was associated with the decrease in general growth rate and the increase in muscle expression of TRα was accompanied with muscle accretion and myofiber hypertrophy, implicating the different roles of TRs in the regulation of growth in large yellow croaker.
... The euthyroid (EU) rats were age-matched littermates of the experimental animals. All the rats analyzed in this study were part of a larger group in which thyroid states were previously checked by the measurement of biochemical and anatomical parameters that are known to be affected by thyroid hormone level alterations [39, 40]. ...
The expression of two cardiac myosin heavy chain (MyHC) isoforms in response to the thyroid status was studied in left ventricles (LVs) of Lewis rats. Major MyHC isoform in euthyroid and hyperthyroid LVs had a higher mobility on SDS-PAGE, whereas hypothyroid LVs predominantly contained a MyHC isoform with a lower mobility corresponding to that of the control soleus muscle. By comparing the MyHC profiles obtained under altered thyroid states together with the control soleus, we concluded that MyHCα was represented by the lower band with higher mobility and MyHCβ by the upper band. The identity of these two bands in SDS-PAGE gels was confirmed by western blot and mass spectrometry. Thus, in contrast to the literature data, we found that the MyHCα possessed a higher mobility rate than the MyHCβ isoform. Our data highlighted the importance of the careful identification of the MyHCα and MyHCβ isoforms analyzed by the SDS-PAGE.
... T3- treated animals presented a body weight that was lower than that of controls only from day 6 to day 9 and from day 24 to day 27 of treatment (Fig. 1A and B). The absence or minimal effects of T3 on body weight of rats were noticed previously (Yu et al. 1998, Soukup et al. 2001). In the present study, it can be explained by the increase in food intake induced by T3 (Fig. 1C). ...
It is well known that thyroid hormone affects body composition; however, the effect of the thyroid hormone receptor beta (TRbeta)-selective thyromimetic GC-1 on this biological feature had not been demonstrated. In the current study, we compared the effects of a 6-week treatment with triiodothyronine (T3; daily injections of 3 or 6 microg/100 g body weight) or GC-1 (equimolar doses) on different metabolic parameters in adult female rats. Whereas all animals gained weight (17-25 g) in a way not basically affected by T3 or GC-1 treatment, only T3 treatment selectively increased food intake (50-70%). Oxygen consumption was significantly and equally increased (50-70%) by T3 and GC-1. Analysis of body composition by dual-energy X-ray absorptiometry (DEXA) revealed that, whereas control animals gained about 80% of fat mass, T3- or GC-1-treated animals lost 70-90 and approximately 20% respectively. Direct analysis of the carcass showed that T3 treatment promoted a 14-74% decrease in fat content but GC-1 treatment promoted only a 15-23% reduction. The gain in lean mass by DEXA and the carcass protein content were not affected by T3 or GC-1 treatment. However, the mass of individual skeletal muscles was negatively affected by T3 but only barely by GC-1. These findings highlight the potential use of GC-1 for the treatment of obesity and the metabolic syndrome.
... Also, the relative heart weight was increased and that of thyroid gland reduced in HT status, while in HY rats, the thyroid glands hypertrophied significantly. These data confirmed the efficacy of the protocol used to induce chronic HT and HY status (Soukup et al. 2001, 2012; Rauchova et al. 2011, 2013). It is worth to note that our experiments were performed on female rats and it was shown that fiber type transition in response to T 3 increased levels can be different in males (Yu et al. 1999). ...
Satellite cells are the myogenic precursor cells of postnatal skeletal muscles. After muscle injury they can proliferate, differentiate, fuse and form myofibres. We have analysed regeneration of distinctly different types of intrafusal fibres in rat muscle spindles. We have introduced the new technique of heterochronous allotransplantation and compared it with the previously used standard autografting method. The allotransplantation method enables one to graft muscles from very young animals; we have used the extensor digitorum longus (EDL) muscles from 2- to 28-day-old rats, which were grafted into EDL muscles of adult inbred recipients. The regenerated "intrafusal" fibres did not express the spindle-specific slow tonic and alpha cardiac-like myosin heavy chain (MyHC) isoforms and they did not exhibit the dual mATPase reaction typical of the nuclear bag2 fibres and the characteristic regional differences in MyHC expression and in the mATPase reaction of nuclear bag1 and nuclear bag2 fibres. On the other hand, they expressed either fast twitch or slow twitch/beta cardiac MyHC isoforms and exhibited an alkali or acid stable mATPase reaction along their whole length, like extrafusal fast type 2 and slow type 1 muscle fibres, respectively. In all regenerated muscle spindles only motor, but no sensory axons were found. More than 85% of muscle spindles in our sample contained regenerated spindle fibres of the same extrafusal fibre type (either type 2 or type 1), in contrast to control muscle spindles, which always contained intrafusal fibres of three different intrafusal fibre types (nuclear bag1, nuclear bag2 and nuclear chain fibres). There were no differences in MyHC expression and mATPase activity between spindle fibres regenerated in grafts taken from young rats of various ages or between allotransplanted and autotransplanted EDL muscles. The present results demonstrate that regenerated "intrafusal" fibres resemble, according to MyHC expression, extrafusal fast or slow muscle fibres. It can thus be concluded that intrafusal satellite cells derived from distinctly different nuclear bag1, nuclear bag2 and nuclear chain fibres show great plasticity, as their MyHC expression can be respecified towards the extrafusal muscle fibre phenotype by foreign alpha-motor innervation.
Titanium dioxide nanoparticles (TiO 2 NPs) are generally used in different types of applications such as the industry of plastics, paper industry, paints, toothpaste, cosmetics, sunscreens, and in various lifestyles, because of the vast range of applications and our daily exposure to these nanoparticles and a lack of information on animal and human health this study was designed to reveal dose and time-dependent effects of TiO 2-NPs on the thyroid gland and kidney functions in male rats. For this study 54, Sprague-Dawley albino adult male rats were classified into three main groups each of 18 rats treated for a particular duration (1,2, and 4) weeks respectively. Each group was subdivided into three subgroups each of six rats treated as follows; group (1) serve as normal control, group (2, and 3) intra-peritoneal treated with TiO 2 NPs (50,200) mg/kg respectively, rats are dissected at the end of each experiment and the weights of thyroid and kidney is measured. The result showed a highly significant decrease (p<0.01) in the thyroid gland and a highly significant increase (p<0.01) in kidney weights and TSH, blood urea, creatinine, and total protein, while a highly significant decrease (p<0.01) inT3 and T4 in all different doses (50,200) mg/kg at durations 1, 2 and 4 weeks. The outcomes of the present study illustrate a significant decrease in serum levels of T4 and T3 with exposure to TiO 2 NPS which disrupts thyroid function, while TiO 2 NPS raises the level of urea, total protein, and creatinine. This could be related to the high dose of TiO2-NPs and duration of the study, which caused degeneration and necrosis of kidney cells and damage to peritubules that led to the prevention of secretion which raised urea levels in the blood, also led to high levels of creatinine and total protein in serum because of the imbalance that occurred in the kidney functions.
Background: Thyroid hormones (TH) thyroxine (T4) and triiodothyronine (T3) are known to be essential for maintaining optimal cognitive ability in adults. TH deprivation (hypothyroidism) or excess (hyperthyroidism) may alter signaling pathways involved in adult hippocampal neurogenesis and synaptic plasticity, thus increasing the risk of neurodegenerative disorders and leading to changes in cognitive performance. Aim: This study aimed to explore the effect of experimental hypo- and hyperthyroidism on the lipid peroxidation and glutathione levels, and the activities of antioxidant system enzymes SOD, catalase (CAT) and glutathione peroxidase (GPx) and glutathione reductase (GR) in the rat hippocampus. Material and Methods: The study included 72 adult male Wistar albino rats which were grouped as follows: (1) control; (2) hypothyroidism [hypothyroidism was induced by intraperitoneal injection of 10 mg/kg/day propylthiouracil (PTU) for 4 weeks]; (3) hyperthyroidism [hyperthyroidism was induced by 4-weeks' thyroxine injection (0.3 mg/kg/day)]. The levels of lipid peroxidation, glutathione, antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) in the hippocampus of rats with hypo- and hyperthyroidism were examined using ELISA techniques. Results: The ELISA analysis results of our study show that in the hyperthyroid and hypothyroid rats, the lipid peroksidasyon levels in the hippocampus did not differ significantly from the control groups (P
We evaluated the evidence in research on the effects of melatonin on hypothyroidism and gonadal development. According to the World Health Organization, thyroid disorders due to iodine deficiency affect about 740 million people worldwide. Hypothyroidism is a thyroid dysfunction characterized by hypometabolism of the gland, with reduced or physiologically normal T3 and T4 serum levels, and high TSH level. This disorder occurs mainly in adult women in the reproductive phase, with a prevalence of 2% among the world's female population, with profound repercussions on gestation and fetal formation. During the gestational period, the thyroid is initially stimulated by high concentrations of human chorionic gonadotrophin; thus, maintaining maternal euthyroidism during pregnancy and lactation is fundamental for fetal growth and development. Besides, the hormones produced by this gland are involved in the formation of various organs, such as the skin, brain and gonads. Hypothyroidism is associated with several menstrual abnormalities, anovulation and hyperprolactinemia, resulting in a high rate of abortions, premature births, placental rupture, and weight-related neonatal deficits. In addition, there are studies showing that hypothyroidism can affect ovarian morphology (number of ovarian follicles) and testicular morphology (changes in the testicular-lumen epithelium). Melatonin is a hormone known to modulate the estrous cycle and pregnancy, and studies show that the exogenous application of melatonin increased T4 levels in female rats and controlled the decrease in T3 serum levels, reverting the sigs of hypothyroidism.
Thyroid hormones have a role in the regulation of hydrogen sulfide (H2S) biosynthesis. In this study, we determined the effects of hyperthyroidism on H2S levels in various tissues and messenger RNA (mRNA) expression of cystathionine‐β‐synthase (CBS), cystathionine‐γ‐lyase (CSE), and 3‐mercaptopyruvate sulfurtransferase (3‐MST) in the liver and muscles of the rat. Sixteen male Wistar rats were divided into the hyperthyroid and the control groups. Hyperthyroidism was induced by adding l‐thyroxine (12 mg/L) to drinking water for a period of 21 days. H2S concentrations in serum, liver, aorta, heart, and soleus muscles, as well as mRNA expressions of CBS, CSE, and 3‐MST in these tissues were measured at Day 21. Hyperthyroid rats had lower H2S levels in the serum compared with controls (14.7 ± 1.4 vs. 25.7 ± 1.6 µmol/L, p < 0.001). Compared with controls, hyperthyroid rats had lower levels of H2S in the aorta (89%), heart (80%), and soleus (103%) muscles, but higher levels in the liver (35%). Hyperthyroidism decreased the ratio of CBS/CSE mRNA expression in the liver and the CSE/CBS mRNA expression in the muscles by decreasing CBS levels in liver (34% cf. controls) and CSE levels in the aorta, heart, and soleus muscles (respectively, 51%, 7%, and 52% cf.). In addition, hyperthyroidism decreased the mRNA expression of 3‐MST in the liver (51%) and aorta (33%), and increased it in the heart (300%) and soleus muscle (182%). In conclusion, hyperthyroidism increased H2S levels in the liver and decreased it in muscles; these effects are at least in part due to increases and decreases in expression of CSE in the liver and muscles, respectively. These data indicate an association between thyroid hormone status and gene expression of the H2S‐producing enzymes in the rat.
It is well known that thyroid hormone (TH) is essential for normal bone growth and development. However, the mechanisms by which TH regulates these processes are poorly understood. Recently, the sympathetic nervous system (SNS) was identified as a potent regulator of bone metabolism. In vivo studies by our group have shown that TH interacts with the SNS to regulate bone mass and structure, and that this interaction involves α2 adrenoceptor (α2-AR) signaling. We also identified the presence of α2A-, α2B-, and α2C-AR subtypes in the epiphyseal growth plate (EGP) of mice. In addition, we found that mice with isolated gene deletion of α2A-AR and α2C-AR (α2A-AR−/− and α2C-AR−/−) show a disorganized EGP, smaller long bones and a delay in endochondral ossification. Moreover, we found that the EGP of α2A-AR−/− and α2C-AR−/− animals respond differently, than those of wild-type animals, to TH excess and deficiency. These in vivo findings strongly suggest that TH also interacts with the SNS to regulate bone growth and development. Through a long bone organ culture system, the present study aims to investigate if TH interacts with the SNS directly in the skeleton, to regulate bone linear growth and if α2C-AR is involved in this process. We evaluated the linear bone growth of the femur and tibia derived from wild-type (WT) and α2C-AR−/− neonate mice for 12 days. We observed that 10⁻⁸ M triiodothyronine (T3) treatment for the whole culture period of twelve days significantly decreased bone linear growth of both femur and tibia only in WT animals. The linear growth of the bones derived from KO animals was not affect by T3 treatment. These in vitro findings suggest that TH locally interacts with the SNS to control bone linear growth and that this interaction involves α2C-AR signaling.
Phaseolus vulgaris seeds were irradiated with UV-A, UV-B and UV-C radiation, and then grown in incubator for 8 days at 25±°C. Hypocotyls of newly germinated embryos were cultured on an MS medium containing 0.5mg/l BA and 1.5mg/l 2,4-D. Callus pieces from both UV treated and non-treated explants were lyophilized then α-amylase inhibitors was extracted with ammonium sulfate buffer under a mechanical stirring and centrifugation. It was dialyzed against water and freeze-dried. Total hydrolytic activity assay was used to determine the reduction in amylase activity when the extracted amylase inhibitor was added to reaction mixture. Results showed that UV-B significantly affected the mean % callus induction and callus fresh weight, also the activity of α-amylase inhibitors extracted from callus pieces of UV treated kidney bean was higher than those obtained from that of non-treated explants and the intact plant.
A simple and rapid luminometric assay for the detection of chemical inhibitors of human thyroid peroxidase (hTPO) activity was developed and validated with 10 model compounds. hTPO was derived from the human thyroid follicular cell line Nthy-ori 3-1 and its activity was quantified by measuring the oxidation of luminol in the presence of hydrogen peroxide (H2O2), which results in the emission of light at 428 nm. In this assay,hTPO activity was shown to be inhibited by 5 known TPO inhibitors and not inhibited by 5 non-inhibitors. Similar results were obtained with porcine TPO (pTPO).The inhibition of hTPO by the model compounds was also tested with guaiacol and Ampliflu Red as alternative indicator substrates. While all substrates allowed the detection of pTPO activity and its inhibition, only the Ampliflu Red and luminol-based methods were sensitive enough to allow the quantification of hTPO activity from Nthy-ori 3-1 cell lysates. Moreover, luminol gave results with a narrower 95% confidence interval and therefore more reliable data.Whole extracts of fast-growing Nthy-ori 3-1 cells circumvent the need for animal-derived thyroid organs,thereby reducing costs, eliminating potential contamination and providing the possibility to study human instead of porcine TPO. Overall, the application of luminol and Nthy-ori 3-1 cell lysate for the detection of the disruption of hTPO activity was found to represent a valuable in vitro alternative and a possible candidate for inclusion within a high throughput integrated testing strategy for the detection of compounds that potentially interfere with normal thyroid function in vivo.
A 30 nm ceria was previously shown to be primarily cleared from systemic circulation into mononuclear phagocyte system organs after its intravenous (IV) administration, where it persisted for 90 days. The aims of these studies were to determine if the biodistribution, persistence, and toxicity of nanocerias are affected by dosing schedule, dose, or particle shape. Given the many demonstrated and ongoing uses of nanocerias; the multitude of applications under investigation; and the many sizes, shapes, and surface functionalizations of ceria; a better understanding of its fate is necessary to advance its safe use. Five and 30 nm cubic/polyhedral ceria and a ceria nanorod (9.9 x 264 nm average diameter and length) were IV infused into rats once. The 5 nm ceria dose was also infused daily for 5 consecutive days. The rats were terminated 1 h to 90 days later. Cerium was determined in multiple organs and blood. Compared to vehicle-infused controls, elevated cerium was seen in all sites. Liver, spleen, and bone marrow (mononuclear phagocyte system components), contained the largest percentage of the dose. When normalized to dose, and compared to results of prior work with these nanocerias, the distribution and retention of repeated and lower doses of 5 and 30 nm ceria and ceria nanorods were not greatly different from much higher doses of the 5 and 30 nm ceria. Higher doses resulted in a greater percentage of uptake by the spleen and bone marrow and a greater percentage of the ceria nanorod dose in the bone marrow 30 days after its administration than the other nanocerias. Overall these results suggest the biodistribution and retention of cerium after IV administration of different sizes, doses, dosing schedules, and nanoceria shapes are more similar than different
To investigate whether thyroid hormone (TH) interacts with the sympathetic nervous system (SNS) to modulate bone mass and structure, we studied the effects of daily T3 treatment, in a supraphysiological-dose, for 12 weeks, on the bone of young-adult mice with chronic sympathetic hyperactivity owing to double-gene disruption of adrenoceptors that negatively regulate norepinephrine release, α2A-AR and α2C-AR (α2A/2C-AR(-/-) mice). As expected, T3 treatment caused a generalized decrease in the areal bone mineral density (aBMD) of WT mice (determined by DXA), followed by deleterious effects on the trabecular and cortical bone microstructural parameters (determined by µCT) of the femur and vertebra, and on the biomechanical properties (maximum load, ultimate load and stiffness) of the femur. Surprisingly, α2A/2C-AR-/- mice were resistant to most of these T3-induced negative effects. Interestingly, the mRNA expression of osteoprotegerin, a protein that limits osteoclast activity, was upregulated and downregulated by T3 in the bone of α2A/2C-AR(-/-) and WT mice, respectively. β1-AR mRNA expression and IGF-1 serum levels, which exert bone anabolic effects, were increased by T3 treatment only in α2A/2C-AR(-/-) mice. As expected, T3 inhibited the cell growth of calvaria-derived osteoblasts isolated from WT mice, but this effect was abolished or reverted in cells isolated from KO mice. Collectively, these findings support the hypothesis of a TH-SNS interaction to control bone mass and structure of young-adult mice, and suggests that this interaction may involve α2-AR signaling. Finally, the present findings offer new insights into the mechanisms through which TH regulates bone mass, structure and physiology.
Thyroid hormones (THs) play multiple roles in the organism and alterations of their levels can result in many pathological changes. Currently, we use hyperthyroid and hypothyroid rats as "models of a diseased organism" and analyze whether n-3 polyunsaturated fatty acids (n-3 PUFA) administration can ameliorate TH-induced pathophysiological changes. We investigate myosin heavy chain composition, calsequestrin levels, changes in cardiac tissue remodeling and cell-to-cell communication, expression of protein kinases, mitochondrial functions, oxidative stress markers and cell death, changes in serum lipid levels, activities of key enzymes of thyroid hormone metabolism, activity of acetylcholine esterase and membrane anisotropy, as well as mobile behavior and thermal sensitivity. Additionally we also mention our pilot experiments dealing with the effect of statin administration on skeletal muscles and sensory functions. As THs and n-3 PUFA possess multiple sites of potential action, we hope that our complex research will contribute to a better understanding of their actions, which can be useful in the treatment of different pathophysiological events including cardiac insufficiency in humans.
This study investigates the in vitro effect of eleven thyroid-active compounds known to affect pituitary and/or thyroid weights in vivo, using the proliferation of GH3 rat pituitary cells in the so-called "T-screen," and of FRTL-5 rat thyroid cells in a newly developed test denoted "TSH-screen" to gain insight into the relative value of these in vitro proliferation tests for an integrated testing strategy (ITS) for thyroid activity. Pituitary cell proliferation in the T-screen was stimulated by three out of eleven tested compounds, namely thyrotropin releasing hormone (TRH), triiodothyronine (T3) and thyroxine (T4). Of these three compounds, only T4 causes an increase in relative pituitary weight, and thus T4 was the only compound for which the effect in the in vitro assay correlated with a reported in vivo effect. As to the newly developed TSH-screen, two compounds had an effect, namely, thyroid-stimulating hormone (TSH) induced and T4 antagonized FRTL-5 cell proliferation. These effects correlated with in vivo changes induced by these compounds on thyroid weight. Altogether, the results indicate that most of the selected compounds affect pituitary and thyroid weights by modes of action different from a direct thyroid hormone receptor (THR) or TSH receptor (TSHR)-mediated effect, and point to the need for additional in vitro tests for an ITS. Additional analysis of the T-screen revealed a positive correlation between the THR-mediated effects of the tested compounds in vitro and their effects on relative heart weight in vivo, suggesting that the T-screen may directly predict this THR-mediated in vivo adverse effect.
Epidemiological studies have demonstrated that n-3 polyunsaturated fatty acid (PUFA) consumption is associated with a reduced risk of atherosclerosis and hyperlipidemia. It is well known that lipid metabolism is also influenced by thyroid hormones. The aim of our study was to test whether n-3 PUFA supplementation (200 mg/kg of body weight/day for 6 weeks given intragastrically) would affect lipid metabolism in Lewis male rats with altered thyroid status. Euthyroid, hypothyroid, and hyperthyroid status of experimental groups was well defined by plasma levels of triiodothyronine, the activity of liver mitochondrial glycerol-3-phosphate dehydrogenase, and by relative heart weight. Fasting blood glucose levels were significantly higher in the hyperthyroid compared to the euthyroid and hypothyroid rats (5.0±0.2 vs. 3.7±0.4 and 4.4±0.2 mmol/l, respectively). In hyperthyroid animals, the concentration of plasma postprandial triglycerides was also increased compared to euthyroid and hypothyroid rats (0.9±0.1 vs. 0.5±0.1 and 0.4±0.1 mmol/l, respectively). On the other hand, hypothyroidism compared to euthyroid and hyperthyroid status was associated with elevated plasma levels of total cholesterol (2.6±0.2 vs. 1.5±0.1 and 1.6±0.1 mmol/l, respectively), LDL cholesterol (0.9±0.1 vs. 0.4±0.1 and 0.2±0.1 mmol/l, respectively) as well as HDL cholesterol (1.6±0.1 vs. 1.0±0.1 and 1.3±0.1 mmol/l, respectively). Supplementation of n-3 PUFA in the present study did not significantly modify either relative heart weight or glucose and lipid levels in any thyroid status.
Calsequestrin is the main calcium binding protein of the sarcoplasmic reticulum, serving as an important regulator of Ca(2+). In mammalian muscles, it exists as a skeletal isoform found in fast- and slow-twitch skeletal muscles and a cardiac isoform expressed in the heart and slow-twitch muscles. Recently, many excellent reviews that summarised in great detail various aspects of the calsequestrin structure, localisation or function both in skeletal and cardiac muscle have appeared. The present review focuses on skeletal muscle: information on cardiac tissue is given, where differences between both tissues are functionally important. The article reviews the known multiple roles of calsequestrin including pathology in order to introduce this topic to the broader scientific community and to stimulate an interest in this protein. Newly we describe our results on the effect of thyroid hormones on skeletal and cardiac calsequestrin expression and discuss them in the context of available literary data on this topic.
Estrogen receptor (ER) and thyroid hormone receptors (TRs) are ligand-dependent nuclear transcription factors that can bind to an identical half-site, AGGTCA, of their cognate hormone response elements. By in vitro transfection analysis in CV-1 cells, we show that estrogen induction of chloramphenicol acetyltransferase (CAT) activity in a construct containing a CAT reporter gene under the control of a minimal thymidine kinase (tk) promoter and a copy of the consensus ER response element was attenuated by cotransfection of TR alpha 1 plus triiodothyronine treatment. This inhibitory effect of TR was ligand-dependent and isoform-specific. Neither TR beta 1 nor TR beta 2 cotransfection inhibited estrogen-induced CAT activity, although both TR alpha and TR beta can bind to a consensus ER response element. Furthermore, cotransfection of a mutated TR alpha 1 that lacks binding to the AGGTCA sequence also inhibited the estrogen effect. Thus, the repression of estrogen action by liganded TR alpha 1 may involve protein-protein interactions although competition of ER and TR at the DNA level cannot be excluded. A similar inhibitory effect of liganded TR alpha 1 on estrogen induction of CAT activity was observed in a construct containing the preproenkephalin (PPE) promoter. A study in hypophysectomized female rats demonstrated that the estrogen-induced increase in PPE mRNA levels in the ventromedial hypothalamus was diminished by coadministration of triiodothyronine. These results suggest that ER and TR may interact to modulate estrogen-sensitive gene expression, such as for PPE, in the hypothalamus.
The effects of 4 weeks of thyroid hormone (3,5,3'-triiodothyronine, T3) treatment on the myosin isoform composition and maximum velocity of unloaded shortening (V0) of single soleus muscle fibres of young (3-6 months) and old (20-24 months) female (149 fibres) and male (200 fibres) rats were studied. Gender-related differences in the up-regulation of fast myosin heavy chain (MyHC) and myosin light chain (MyLC) isoforms were observed. In the female hyperthyroid rats, pure type I fibres and fibres co-expressing type I and type IIA MyHC (type I/IIA fibres) predominated. Some fibres expressed an alpha cardiac-like MyHC isoform either purely (alpha cardiac-like fibre type) or in co-expression with IIA MyHC (alpha cardiac-like/IIA fibre type). In the male hyperthyroid rats, on the other hand, all fibres were either type I/IIA or type I/IIAX. The relative quantities of fast MyLC isoforms in type I/IIA and type I/IIAX fibres was higher in female than in male hyperthyroid rats. V0 was similar in male and female control rats, and decreased with age in both genders (P<0.001). After T3 treatment, the average V0 increased (P<0.001) in females with a concomitant up-regulation of fast MyHC and fast MyLC isoforms irrespective of age. The average V0 of the pooled fibres was higher (P<0.001) in female than in male hyperthyroid rats at both ages. In conclusion, gender- and age-related differences were observed in the regulatory influence of 4 weeks' T3 treatment on myosin isoform composition and V0 in soleus fibres. These differences are presumably related to an interaction of thyroid and sex hormones in the regulation of myosin gene expression.
We have shown previously that continuous (6 days) intracerebroventricular (ICV) leptin infusion in normal rats resulted in decreases in food intake and body weight. A reduction of food intake imposed on control rats (pair-feeding), aimed at mimicking leptin-induced hyperphagia, produced a marked decrease in the expression of muscle uncoupling protein-3 (UCP-3), whereas ICV infusion of leptin prevented such a decrease in UCP-3. To investigate an involvement of thyroid hormones in this effect of leptin, plasma levels of these hormones were determined in ICV leptin-infused, ICV vehicle-infused ad libitum fed or pair-fed controls. ICV leptin infusion and pair-feeding resulted in decreased plasma thyroid-stimulating hormone (TSH) and T4 levels relative to ad libitum fed controls. ICV leptin infusion maintained plasma levels of T3, but the levels were decreased by pair-feeding. The activity of the enzyme (hepatic 5'-monodeiodinase) responsible for T4/T3 conversion was measured. In the leptin-infused group, the activity of 5'-monodeiodinase was maintained at the values measured in ad libitum fed rats; in pair-fed rats, activity was reduced. Thus, conversion of T4 to T3 is decreased by pair-feeding, whereas such is not the case during leptin infusion. To further substantiate an involvement of thyroid hormones in the effect of leptin on muscle UCP-3 expression, hypothyroid rats were ICV infused with leptin or vehicle. It was observed that in hypothyroid rats, ICV leptin was unable to maintain muscle UCP-3 expression at values measured in ad libitum fed controls. These results suggest that central leptin stimulates T3 production via an activation of T4 to T3 conversion, and that this stimulation could be responsible for the effect of leptin on muscle UCP-3 expression. Thyroid hormones could thus be important mediators of the effect of leptin on energy expenditure.
Preparations of rat-liver mitochondria catalyze the oxidation of exogenous NADH by added cytochrome c or ferricyanide by a reaction that is insensitive to the respiratory chain inhibitors, antimycin A, amytal, and rotenone, and is not coupled to phosphorylation. Experiments with tritiated NADH are described which demonstrate that this "external" pathway of NADH oxidation resembles stereochemically the NADH-cytochrome c reductase system of liver microsomes, and differs from the respiratory chain-linked NADH dehydrogenase. Enzyme distributation data are presented which substantiate the conclusion that microsomal contamination cannot account for the rotenone-insensitive NADH-cytochrome c reductase activity observed with the mitochondria. A procedure is developed, based on swelling and shrinking of the mitochondria followed by sonication and density gradient centrifugation, which permits the separation of two particulate subfractions, one containing the bulk of the respiratory chain components, and the other the bulk of the rotenone-insensitive NADH-cytochrome c reductase system. Morphological evidence supports the conclusion that the former subfraction consists of mitochondria devoid of outer membrane, and that the latter represents derivatives of the outer membrane. The data indicate that the electron-transport system associated with the mitochondrial outer membrane involves catalytic components similar to, or identical with, the microsomal NADH-cytochrome b(5) reductase and cytochrome b(5).
Extensor digitorum longus (EDL) muscles from 2- to 28-day-old rats were grafted into EDL muscles of adult inbred recipients (n = 8). At 1-6 months after the operation, experimental muscles were excised and the ultrastructure and innervation of regenerated muscle spindles was examined. Regenerated muscle spindles (n = 36) in isografted EDL muscles contained 4.3 +/- 0.2 (mean +/- SEM) encapsulated muscle fibres. These "intrafusal" muscle fibres lacked nuclear bag and nuclear chain accumulations, which are characteristic of normal muscle spindles; thus, they rather resembled thin encapsulated extrafusal muscle fibres. In the same sample, myelinated axons were found in 33 (92%) muscle spindles, but no sensory terminals were found. These findings demonstrate that regenerated spindles in isografted EDL muscles were not reinnervated by spindle-specific sensory axons, but exclusively by motor axons. Typical intracapsular motor endplates (MEPs) were found in one third of regenerated spindles examined. Their motor terminals contained accumulated mitochondria and synaptic vesicles. As is characteristic for MEPs, axolemma and sarcolemma were separated by a synaptic cleft about 60 nm wide that contained a basal lamina. The underlying sarcolemma formed either small infoldings or none at all, and the subsynaptic area contained only small subsarcolemmal accumulations of mitochondria. It is apparent that the structures described here as "regenerated muscle spindles" do not perform their normal physiological function as stretch receptors because they lack the sensory innervation. The present results show that regeneration and reinnervation in heterochronous isografts corresponds to that previously described in autotransplanted free muscle grafts. The results also show that, during muscle spindle regeneration, intrafusal satellite cells develop into extrafusal-like muscle fibres, apparently due to their motor innervation.
In this study, plasma leptin concentrations were measured in rats artificially rendered hyper- or hypothyroid by administration of thyroxine or TRH, by administration of methimazole, or by thyroidectomy. Compared with those in untreated controls, leptin immunoreactivity was not affected in the hyperthyroid state, but was significantly increased in hypothyroid animals. Methimazole administration for longer time periods caused a stepwise increase in plasma leptin immunoreactivity. Greatest leptin concentrations were seen after 28 days of methimazole. Seven days after withdrawal of the methimazole, leptin concentrations no longer differed from those observed in control animals. In hypothyroid animals, expression of leptin mRNA was increased in both retroperitoneal and epididymal adipose tissue, whereas no difference was seen for subcutaneous or mesenteric fat. Incubation of rat leptin with plasma of eu- or hypothyroid rats and subsequent HPLC analysis of leptin plasma peaks gave no indication of an altered hormone stability. We conclude that, in hypothyroid rats, leptin concentrations may be increased as a result of stimulated leptin synthesis in retroperitoneal and epididymal adipose tissue.
Satellite cells are the myogenic precursor cells of postnatal skeletal muscles. After muscle injury they can proliferate, differentiate, fuse and form myofibres. We have analysed regeneration of distinctly different types of intrafusal fibres in rat muscle spindles. We have introduced the new technique of heterochronous allotransplantation and compared it with the previously used standard autografting method. The allotransplantation method enables one to graft muscles from very young animals; we have used the extensor digitorum longus (EDL) muscles from 2- to 28-day-old rats, which were grafted into EDL muscles of adult inbred recipients. The regenerated "intrafusal" fibres did not express the spindle-specific slow tonic and alpha cardiac-like myosin heavy chain (MyHC) isoforms and they did not exhibit the dual mATPase reaction typical of the nuclear bag2 fibres and the characteristic regional differences in MyHC expression and in the mATPase reaction of nuclear bag1 and nuclear bag2 fibres. On the other hand, they expressed either fast twitch or slow twitch/beta cardiac MyHC isoforms and exhibited an alkali or acid stable mATPase reaction along their whole length, like extrafusal fast type 2 and slow type 1 muscle fibres, respectively. In all regenerated muscle spindles only motor, but no sensory axons were found. More than 85% of muscle spindles in our sample contained regenerated spindle fibres of the same extrafusal fibre type (either type 2 or type 1), in contrast to control muscle spindles, which always contained intrafusal fibres of three different intrafusal fibre types (nuclear bag1, nuclear bag2 and nuclear chain fibres). There were no differences in MyHC expression and mATPase activity between spindle fibres regenerated in grafts taken from young rats of various ages or between allotransplanted and autotransplanted EDL muscles. The present results demonstrate that regenerated "intrafusal" fibres resemble, according to MyHC expression, extrafusal fast or slow muscle fibres. It can thus be concluded that intrafusal satellite cells derived from distinctly different nuclear bag1, nuclear bag2 and nuclear chain fibres show great plasticity, as their MyHC expression can be respecified towards the extrafusal muscle fibre phenotype by foreign alpha-motor innervation.
The alpha 2 and beta 2 adrenergic receptors, both of which are activated by epinephrine, but which can be differentiated by
selective drugs, have opposite effects (inhibitory and stimulatory) on the adenylyl cyclase system. The two receptors are
homologous with each other, rhodopsin, and other receptors coupled to guanine nucleotide regulatory proteins and they contain
seven hydrophobic domains, which may represent transmembrane spanning segments. The function of specific structural domains
of these receptors was determined after construction and expression of a series of chimeric alpha 2-,beta 2-adrenergic receptor
genes. The specificity for coupling to the stimulatory guanine nucleotide regulatory protein lies within a region extending
from the amino terminus of the fifth hydrophobic domain to the carboxyl terminus of the sixth. Major determinants of alpha
2- and beta 2-adrenergic receptor agonist and antagonist ligand binding specificity are contained within the seventh membrane
spanning domain. Chimeric receptors should prove useful for elucidating the structural basis of receptor function.
We have studied the effects of triiodothyronine (T3) on heart function, on the myocardial oxidative pentose phosphate pathway, and on heart weight in spontaneously hypertensive (SHR) rats. Another aim was to examine whether these T3-effects may be reversible. T3 was administered daily (0.2 mg/kg s.c.) for 14 days. Compared to the untreated SHR controls, T3 induced an increase in heart rate (beats/min) from 357 +/- 10 (n = 17) to 553 +/- 10 (n = 17), in the pressure-rate-product (mm Hg/min) from 78 400 +/- 4500 (n = 15) to 113 700 +/- 4800 (n = 15), and in the heart weight/body weight ratio (mg/g) from 4.2 +/- 0.2 (n = 20) to 5.8 +/- 0.2 (n = 19). The activity of myocardial glucose-6-phosphate dehydrogenase, the first and rate-limiting enzyme of the oxidative pentose phosphate pathway (units/g protein), was elevated from 4.2 +/- 0.2 (n = 9) to 7.0 +/- 0.6 (n = 9) after 14 days of T3-treatment, while the activity of 6-phosphogluconate dehydrogenase, one of the following enzymes in the pathway, was not altered appreciably. These changes returned to the respective control values when T3-treatment was discontinued for 14 days. Our results demonstrate that T3 had a positive chronotropic effect and induced an additional heart enlargement in an animal model with already established cardiac hyperfunction and hypertrophy. The effects on heart function and weight, which were fully reversible, were not as pronounced as in normal Sprague-Dawley rats.
Investigation of thyroid glands from 500 male and 500 female Sprague-Dawley rats, at time points of 8, 17, 30, 56, and 108 weeks of toxicity studies conducted at the Huntingdon Research Centre between 1981 and 1984, revealed age-related structural and functional changes that have previously not been well documented. The number of ultimobranchial cysts decreased with age, while area(s) of C-cell hyperplasia appeared with age. Beginning at 56 weeks, some of the thyroid follicles were hyperdistended with colloid, had irregular lumens, and were lined by flattened epithelium. These follicles had clumped, granular, and stratified colloid. Follicular tumors were found in 8% of the males and 6% of the females at 108 weeks. There was an increase in absolute thyroid weights (males from 21.8 +/- 4.0 g to 46.5 +/- 19.05 g, females from 17.2 +/- 4.53 g to 41.7 +/- 26.92 g) and body weights (males from 382.0 +/- 70.6 g to 806.0 +/- 120.7 g, females from 220.0 +/- 21.0 g to 495.0 +/- 127.3 g) with age in both sexes, but the relative thyroid weights were not significantly affected. Negative allometry was observed. With an increase in the age of the rats, there was a decrease in the height of the follicular epithelium and an increase in the internal follicular diameter and the total number of follicles. No prediction for sex could be detected. Serum T3 and T4 concentrations were constant until 56 weeks of age, but at 108 weeks, the values were markedly reduced (in males, serum T3 concentration decreased from 91.60 +/- 13.970 ng/100 ml to 32.90 +/- 10.878 ng/100 ml, and in females, from 90.80 +/- 11.338 ng/100 ml to 48.10 +/- 8.875 ng/100 ml; in males, serum T4 concentration decreased from 5.94 +/- 0.679 microgram/100 ml to 3.04 +/- 0.604 microgram/100 ml, and in females, from 4.59 +/- 0.717 microgram/100 ml to 2.77 +/- 0.786 microgram/100 ml). The data suggest that the thyroid function of Sprague-Dawley rats reduces as the rats age.
The aim of this study was to contrast competing influences, hypothyroidism and hindlimb suspension, on myosin heavy chain (MHC) expression studied at the protein level and mRNA level. Female Sprague-Dawley rats were assigned to either normal control (NC), normal suspended (NS), or hypothyroid (thyroidectomized) control (TC) and suspended (TS) groups. NS and TS animals were suspended for 14 days following which myofibrils and total RNA were purified from the hindlimb muscles. In the soleus and vastus intermedius (VI), there was an increase in type I MHC and a decrease in type IIa MHC in both the TC and TS groups and a decrease in type I and increase in type IIa MHC in the NS group. At the mRNA level, similar shifts were observed with the exception that 1) the increased type IIa MHC seen in the soleus and VI of the NS animals was not accompanied by an increase in IIa mRNA and 2) type IIb mRNA was increased in the NS soleus without concomitant changes in IIb protein levels. These data suggest the following: 1) a hypothyroid state predominates over mechanical unweighting factors in the control of MHC distribution in slow muscles; and 2) translational or posttranslational factors may be important in the regulation of type IIa and IIb MHC expression during hindlimb suspension.
The effects of a combined treatment with supraphysiological doses of the thyroid hormone T3 (15 micrograms/kg BW/day, s.c.) and high doses of a predominant beta 1-blocker (atenolol, 12.5 and 25 mg/kg BW, 3X/day, s.c.) or a non-specific beta-blocker (propranolol, 5 mg/kg BW s.c. and 33 mg/kg BW p.o., each 3X/day) on energy intake, body composition and the heart were studied in overfed rats with an increased body fat content. The goal of the study was to investigate whether the above treatment constitutes a therapy for obesity in that T3 causes weight and fat loss and the beta-blockers prevent the unwanted T3-effects on the heart (tachycardia and increased heart weight). T3 did not increase energy intake above the level seen in overfed animals. It caused loss of body weight due to loss of fat but not protein, an increase in interscapular brown adipose tissue (IBAT) weight and fat, tachycardia and an increase in heart weight. Atenolol and propranolol blocked T3-induced tachycardia. With the exception of the highest propranolol dose which abolished the T3-induced increase in IBAT fat content, the beta-blockers did not modify the other T3 effects. Thus, in spite of the weight and fat loss and the lack of significant protein loss and tachycardia observed under T3/high dose beta-blockers treatment, the T3-induced increase in heart weight makes this treatment unsuitable as a therapy for obesity.
The inotropic response of rat hearts in vivo was tested by infusion of 2 mmol/kg/h calcium chloride after 14 days of daily 3,3',5-triiodo-L-thyronine (T3) treatment and 14 days following discontinuation of T3 treatment. The hyperthyroid state was characterized by marked cardiac hypertrophy (57% increase in the heart weight/body weight ratio) which was more pronounced in the right ventricle (63% increase). Heart rate and cardiac output index were elevated by 56 and 63%, respectively, and total peripheral resistance was reduced by 40%. Left ventricular systolic pressure (LVSP) was elevated by 15%, the maximal rate of rise in left ventricular pressure (LV dp/dtmax) by 106%, and LV pressure-volume performance by 192%. Right ventricular systolic pressure (RVSP) was elevated by 71%, RV dp/dtmax by 126%, and RV pressure-volume performance by 371%. Intravenous infusion of calcium induced an elevation in heart rate and LV dp/dtmax, the increase of the latter was less pronounced than in the control heart. After 14 days subsequent to discontinuation of T3 treatment, there was a regression of cardiac hypertrophy. However, the LV was still hypertrophied by 12% and the RV by 24%. Heart rate and contractility were normal. The pressure-volume performance of both LV and RV was still enhanced by 24 and 18%, respectively. The inotropic response of the LV to calcium infusion was similar to that of the normal heart. Thus, 14 days after discontinuation of T3 treatment, the regression of cardiac hypertrophy was not complete, although heart rate and contractility as well as the inotropic response to calcium, were normal. The remaining cardiac hypertrophy correlated with the still existing elevation in the pressure-volume performance.
Muscle capillarity, mean and maximal diffusion distances and muscle fibre composition were evaluated in frozen sections stained for myosin ATPase of the soleus and the white area of the gastrocnemius medial head (gastrocnemius) of rats made hypothyroid by the injection of propylthiouracil (PTU) (50 mg kg-1) every day for 21 or 42 days. Oxygen consumption in the presence of excess ADP and Pi with pyruvate plus malate as substrates and the activity of cytochrome c oxidase were measured in muscle homogenates. Treatment with PTU decreased body oxygen consumption and the concentration of triiodothyronine in plasma. The capacity of the soleus and gastrocnemius muscles' homogenates to oxidize pyruvate plus malate and their cytochrome c oxidase activity were reduced after 21 or 42 days of treatment with PTU. Fibre composition in the soleus muscle was changed by treatment with PTU. There was a decrease in the proportion of type IIa or fast glycolytic oxidative fibres and an increase in type I or slow oxidative fibres. After 21 days of PTU administration there was also an increase in the proportion of fibres classified as IIc. The changes in fibre composition are believed to be the result of changes in the types of myosin synthesized by the fibres. Therefore, the fibres classified as IIc are, most probably, IIa fibres in the process of changing their myosin to that of the type I fibres. No changes in fibre composition were evident in the white area of the gastrocnemius medial head, an area made up of IIb or fast glycolytic fibres. The indices of capillarity: capillary density and capillary to fibre ratio, as well as mean and maximal diffusion distances from the capillaries, were not changed by the treatment with PTU in the muscles studied. The lack of changes in capillarity in spite of significant changes in oxidative capacity indicates that in skeletal muscle capillarity is not necessarily related to the oxidative capacity of the fibres.
Muscle fibre composition and capillarity were evaluated in frozen sections stained for myosin ATPase of the soleus and the white area of the medial head of the gastrocnemius of rats made hyperthyroid by injections of triiodothyronine (300-400 micrograms/kg body weight, every other day) for 2, 3 and 4 weeks. O2 consumption of homogenates of these muscles in the presence of excess inorganic phosphate (Pi) and ADP with pyruvate and malate as substrates was also measured. Increased oxidative capacity was observed in the soleus homogenates of hyperthyroid animals after 2 weeks of treatment while no changes were observed in the oxidative capacity of the homogenates of the white area of the medial head of the gastrocnemius, even after 4 weeks of treatment. Hyperthyroid animals showed a greater capillarity than controls in both muscles. In the soleus this was evident after 2 weeks of treatment while in the white area of the medial head of the gastrocnemius, it was evident only after 4 weeks of treatment. Fibre composition was affected in the soleus after 4 weeks of treatment. In control animals two fibre types were present in the soleus: slow-twitch oxidative fibres (s.o. or type I fibres) with a high ATPase activity after acid pre-incubation and fast-twitch glycolytic oxidative fibres (f.o.g. or type IIa fibres) with a low ATPase activity after acid pre-incubation. In the soleus of the hyperthyroid animals, a third fibre type with intermediate ATPase activity after acid pre-incubation was also present. This most probably represents a change in the type of myosin being synthesized by some fibres. No changes in fibre composition were observed in the white area of medial head of the gastrocnemius which was made up of only fast-twitch glycolytic fibres (f.g. or type IIb fibres). The changes in oxidative capacity and capillarity in the soleus preceded and did not seem to be related to the changes in the type of myosin being synthesized. The increased capillarity found in the white area of the medial head of the gastrocnemius of the hyperthyroid animals, in the absence of an increase in the oxidative capacity, indicates that the latter is not the only factor that determines capillarity in skeletal muscle.
1. The effects of 4 weeks of thyroid hormone treatment on contractile, enzyme-histochemical and morphometric properties and on the myosin isoform composition were compared in the slow-twitch soleus and the fast-twitch extensor digitorum longus (EDL) muscle in young (3-6 months) and old (20-24 months) male rats. 2. In the soleus of untreated controls, contraction and half-relaxation times of the isometric twitch increased by 19-32% with age. The change in contractile properties was paralleled by an age-related increase in the proportions of type I fibres and type I myosin heavy chain (MHC) and slow myosin light chain (MLC) isoforms. 3. In the EDL of controls, contraction and half-relaxation times were significantly prolonged (21-38%) in the post-tetanus twitch in the old animals. No significant age-related changes were observed in enzyme-histochemical fibre-type proportions, although the number of fibres expressing both type IIA and IIB MHCs and of fibres expressing slow MLC isoforms was increased in the old animals. 4. Serum 3,5,3',5'-tetraiodothyronine (T4) levels were lower (34%) in the old animals, but the primary byproduct of T4, 3,5,3'-triiodothyronine (T3), did not differ between young and old animals. 5. The effects of 4 weeks of thyroid hormone treatment were highly muscle specific, and were more pronounced in soleus than in EDL, irrespective of animal age. In the soleus, this treatment shortened the contraction and half-relaxation times by 35-57% and decreased the number of type I fibres by 66-77% in both young and old animals. In EDL, thyroid hormone treatment significantly shortened the contraction time by 24%, but the change was restricted to the old animals. 6. In conclusion, the ability of skeletal muscle to respond to thyroid hormone treatment was not impaired in old age and the age-related changes in speed of contraction and enzyme-histochemical properties and myosin isoform compositions were diminished after thyroid hormone treatment in both the soleus and EDL.
Extensor digitorum longus (EDL) muscles from rats at various intervals after birth were grafted into EDL muscles of adult recipients. Three to twelve months after the operation, host muscles containing the grafts were removed and examined for the presence of muscle spindles in the graft. The aim of the study was to establish when muscle spindles become capable of regeneration during development. Regenerated muscles grafted during the first week after birth were virtually spindleless. Grafts of muscles transplanted 10 and 15 days postnatally contained only 5-8 muscle spindles on average. In contrast, the regenerated grafts originating from muscles of 24- and 28-day-old rats were spindle-rich as in mature muscle grafts; the number of spindles in the transplanted EDL muscles (25.0 +/- 2.3; mean +/- SE) attained values comparable to free standard autografts of these muscles in adult animals. Thus, the critical period after grafting, which also involves the loss of a vascular supply, is considerably longer than the critical period for muscle-spindle survival after nerve injury. Fifteen days after birth, when muscle spindles still survive denervation, only a few regenerated spindles were present in the individual muscle regenerates. We assume that the low resistance of immature spindle capsules to ischaemia accounts for their massive degeneration and abortive spindle regeneration in grafts from 10- to 15-day-old rats.
The effects of 4 and 8 weeks of thyroid hormone (3,5,3'-triiodothyronine, T3) treatment on skeletal muscles of young (3-6 months) male Wistar rats were investigated in the present study. In the slow-twitch soleus, contraction and half-relaxation times of the isometric twitch were significantly shorter in hyperthyroid rats than in the control group, and twitch duration was shorter in rats treated with T3 for 8 weeks than for 4 weeks. All single soleus muscle fibres from hyperthyroid rats co-expressed types I and IIA myosin heavy chains (type I/IIA fibres) or type I, IIA and IIX myosin heavy chains (type I/IIAX fibres), while only type I MyHC fibres were isolated from the controls. A significantly higher content of type IIA myosin heavy chain and fast myosin light chain isoforms was observed in soleus fibres from the 8-week than from 4-week T3 group. There was no significant difference in maximum velocity of unloaded shortening (V0) between type I myosin heavy chain fibres from controls (1.12 +/- 0.46 muscle lengths s-1, n = 48) and type I/IIA myosin heavy chain fibres from the 4-1.09 +/- 0.36 muscle length s-1, n = 33) and 8-week (1.03 +/- 0.31 muscle lengths s(-1), n = 31) groups, but type I/IIAX fibres from the 8-week T3 group had significantly higher V0 (1.56 +/- 0.10, n = 5) than type I from control and type I/IIA from hyperthyroid rats. In the fast-twitch extensor digitorum longus, neither myosin isoform composition, twitch duration nor V0 was affected by 4 or 8 weeks of T3 exposure. In conclusion, a dramatic and exposure duration-dependent change in the contractile speed of the isometric twitch and the expression of fast myosin isoforms was observed in soleus, but not in extensor digitorum longus, in response to T3 treatment. Long-term T3 treatment had relatively less influence, however, on V0 at the single cell level in spite of the dramatic increase in fast myosin isoforms.
Leptin, the product of the ob gene, is secreted by adipocytes and has been shown to decrease appetite and increase energy expenditure. Leptin mRNA in adipocytes correlates with body wt, and serum leptin levels correlate with body fat. Alterations in thyroid status are frequently associated with changes in body wt. To evaluate the possible influence of thyroid status on the leptin system, we have measured serum leptin concentrations in thyroidectomized rats infused either with placebo, or with different doses of T4 (0.8 to 8.0 microg/100 g body wt per day) or T3 (0.25 to 2.0 microg/100 g body wt per day), covering a wide range of thyroid hormone concentrations, from overt hypothyroidism to hyperthyroidism. Intact animals infused with placebo were used as euthyroid controls. Infusion of T4 or T3 into thyroidectomized rats resulted in a decrease in serum leptin levels with respect to the thyroidectomized animals infused with placebo. When compared to the control group, serum leptin levels were decreased in the groups infused with the higher T4 and T3 doses, and tended to be elevated in the thyroidectomized animals infused with placebo. The leptin/body wt ratio was markedly increased in thyroidectomized rats infused with placebo, and decreased in the animals infused with the higher thyroid hormone doses. In conclusion, thyroid hormones exert a negative influence on serum leptin concentrations, which is greater than expected by the changes in body wt The precise mechanism of this influence remains to be elucidated.
The mitochondrial phenotype within cardiac muscle cells is dramatically altered by thyroid hormone. We report here that this can be accounted for, in part, by modifications in the rate of mitochondrial protein import. The import of matrix-localized precursor proteins malate dehydrogenase (MDH) and ornithine carbamoyltransferase was augmented, whereas the insertion of the outer membrane protein Bcl-2 was unaffected by thyroid hormone treatment. Coincident with increases in the import of these matrix-localized precursors were thyroid hormone-induced elevations in the outer membrane receptor Tom20 and the matrix heat-shock protein mthsp70. The phospholipid cardiolipin was not involved in mediating the thyroid hormone-induced increase in import, as judged from adriamycin inhibition studies. When the import reaction was supplemented with rat heart cytosol, we found that 1) MDH import was stimulated, but Bcl-2 import was inhibited and 2) thyroid hormone did not influence the effect of the cytosol on import rates. Thus distinct requirements exist for the mitochondrial import of precursor proteins, destined for different organellar compartments. Although import of these matrix-localized proteins was augmented by thyroid hormone treatment, the proteolysis of matrix proteins was unaffected as indicated by the degradation of cytob2(167)RIC-dihydrofolate reductase, a chimeric protein missorted to the matrix. Thus our data indicate that at least some thyroid hormone-induced modifications of the mitochondrial phenotype occur due to the compartment-specific upregulation of precursor protein import rates, likely mediated via changes in the expression of protein import machinery components.
The physiological consequences and mechanism(s) for thyroid hormone-induced alterations in serum leptin are not known. To address this, leptin expression in rats was evaluated in relationship to food intake, fat mass, and body temperature in rats with pharmacologically altered thyroid status. Total body weight, food intake, and temperature were decreased in hypothyroid rats. Fat weight was decreased in both chronically hypothyroid and hyperthyroid rats (n = 6/group). Serum leptin was linearly correlated with fat weight, epididymal and retroperitoneal fat leptin mRNA concentration, but not total body weight. Serum leptin was decreased in the chronically hyperthyroid rats. When fat weight was used as a covariant, serum leptin was not different between the three groups. Epididymal fat leptin mRNA was higher in euthyroid (n = 7) than in hypothyroid and hyperthyroid rats. Retroperitoneal fat leptin mRNA was not affected by thyroid status. A positive linear relationship between food intake and free triiodothyronine (FT3) index was observed, but not between food intake and serum leptin alone. In a time course study, serum leptin, epididymal fat leptin mRNA content, and fat weight did not change within 24 hours of high-dose triiodothyronine (T3) (n = 6/group), but both temperature and epididymal fat S14 mRNA content rapidly increased. These findings demonstrate that thyroid state influences circulating leptin levels, but primarily does so indirectly through the regulation of fat mass. Leptin does not influence core body temperature across thyroidal state. Finally, thyroid state is more important to regulate food intake, through an as yet undefined mechanism, than are thyroid state-associated changes in serum leptin.
In this study, plasma leptin concentrations were measured in rats artificially rendered hyper- or hypothyroid by administration of thyroxine or TRH, by administration of methimazole, or by thyroidectomy. Compared with those in untreated controls, leptin immunoreactivity was not affected in the hyperthyroid state, but was significantly increased in hypothyroid animals. Methimazole administration for longer time periods caused a stepwise increase in plasma leptin immunoreactivity. Greatest leptin concentrations were seen after 28 days of methimazole. Seven days after withdrawal of the methimazole, leptin concentrations no longer differed from those observed in control animals. In hypothyroid animals, expression of leptin mRNA was increased in both retroperitoneal and epididymal adipose tissue, whereas no difference was seen for subcutaneous or mesenteric fat. Incubation of rat leptin with plasma of eu- or hypothyroid rats and subsequent HPLC analysis of leptin plasma peaks gave no indication of an altered hormone stability. We conclude that, in hypothyroid rats, leptin concentrations may be increased as a result of stimulated leptin synthesis in retroperitoneal and epididymal adipose tissue.
This review summarizes the effects of altered thyroid hormone levels on the expression of myosin isoforms and contractility in single muscle fibres from fast- and slow-twitch muscles from young and old male and female rats. The differences between male and female hyperthyroid soleus muscles are suggested to be related to an interaction of thyroid hormones and sex hormones in the regulation of myosin gene expression. Additionally, the mismatch between the protein and mRNA levels of MyHCs between male and female hyperthyroid extensor digitorum longus (EDL) muscles raises the possibility of a gender-related difference in post-transcriptional, translational or post-translational regulation of MyHC isoforms by T3.
The 2-D stereology can be used advantageously in the case of muscle cross sections stained by routine histochemical and immunocytochemical methods, such as mATPase reaction, when the quality of the image is often not sufficient for using image analysis techniques without considerable individual intervention. Other advantages of stereological methods in muscle morphometry are that measurements are made directly on specimens under the microscope and in their simplest arrangement they do not require sophisticated and expensive technical equipment. Furthermore, unbiased results are obtained, no segmentation and edge effect problems arise and the quantity of work invested in stereological estimation is reasonable. Therefore, we have used the stereological methods as our standard technique for assessment of fibre type composition in regenerated soleus muscles grafted from 21- to 28-day-old rats into fast EDL muscles of adult inbred recipients with different plasma levels of thyroid hormones.
We examined a possible mechanistic interaction between leptin and thyroid hormones in rats with hypothyroidism induced by thyroidectomy (TX) and propylthiouracil administration. In study 1, the TX rats were treated by vehicle (V, n = 9) or by recombinant murine leptin (L, 0.3 mg. kg(-1). day(-1), n = 9) or were pair-fed (PF, n = 9) against L. In study 2, the TX rats were all given 3, 3'5'-triiodo-L-thyronine (T(3)) replacement (T, 5 microg. kg(-1). day(-1)) to correct hypothyroidism. They were then subdivided into three groups, namely, vehicle (T+V, n = 9), leptin (T+L, n = 10), and pair-feeding (T+PF, n = 9), similar to study 1 except for T(3) (T). Reduced food consumption and weight gain in the TX rats were reversed by T(3) replacement. Leptin suppressed food intake in the TX rats regardless of T(3) replacement. O(2) consumption (VO(2)) and CO(2) production (VCO(2)) were reduced in TX rats (P < 0.05 vs. normal) but were normalized by either T(3) or leptin treatment. T+L additively increased VO(2) and VCO(2) (P < 0.05 vs. TX, T(3), and L). The respiratory exchange ratio was unaltered in TX rats, with and without T(3), but was significantly reduced by L or T+L treatments. These results indicate that the metabolic actions of leptin are not dependent on a normal thyroid status and that the effects of leptin and T(3) on oxidative metabolism are additive.
Expression of the muscle phenotype is the result of interaction between intrinsic and extrinsic factors, the latter including innervation, mechanical influences and hormonal signals. This minireview summarizes some of the current knowledge regarding the regulation of myosin heavy chain (MHC) isoform transitions during muscle development and regeneration. It describes the role of genetic factors, neural and mechanical influences and it focuses on the contribution of thyroid hormones to the differentiation of muscle fiber phenotypes as shown by the regulation of the expression of MHC isoforms and development of myofibrillar ATPase activity. Finally, it shortly summarizes results regarding the differentiation of MHC isoforms in regenerated muscle fibers of the graft after heterochronous isotransplantation in rats with different thyroid status.
The ultrastructure of regenerating intrafusal and extrafusal fibers was studied 18 h to 30 days after heterochronous isotransplantation, in which bupivacaine-treated extensor digitorum longus (EDL) or soleus muscles from early postnatal rats were intramuscularly grafted into EDL muscles of adult inbred recipients. As in other models of mammalian muscle regeneration, surviving satellite cells gave rise to presumptive myoblasts, multiplying within the preserved basal lamina tubes at day 4 after grafting. Myoblasts fused to form myotubes with central myonuclei by day 6 after grafting. Extrafusal myotubes differentiated into thin muscle fibers by day 8, which progressively increased in diameter and their nuclei became localized subsarcolemmally from day 13 onwards. The basal laminae of some intrafusal fibers already contained one or more nascent myotubes by day 4 after grafting. Regenerated intrafusal fibers lacked the typical nuclear accumulations and their number varied from one to eight fibers per spindle; additional fibers formed in the periaxial space or between layers of the capsule. Regenerated muscle spindles usually had a thinner outer capsule and a reduced inner capsule and periaxial space. The present study demonstrates that extrafusal and intrafusal muscle fibers degenerate and regenerate after heterochronous isotransplantation in a manner similar to that in standard grafts. However, the time course is slightly different. Degeneration was completed by day 5 after grafting as in free grafts, but the regeneration of extrafusal and intrafusal fibers started 1 or 2 days earlier, apparently because of the rapid and facilitated revascularization from the host muscle compared to that of standard grafts.
Fibre types in the regenerated soleus and EDL isografted into EDL muscle in rats with altered thyroid status
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Changes in the proportion of type 1, 2A, 2X/D and 2B muscle fibres in regenerating grafts in rats with experimentally changed thyroid status
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Absence of thyroid hormones down regulates the expression of fast myosin heavy chain (MyHC) isoforms in regenerating soleus muscle isografted into fast extensor digitorum longus muscle
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Institute of Physiology
- . T Dr
- Soukup
Dr. T. Soukup, Institute of Physiology, Czech Academy of Sciences, Vídeňská 1083, CZ-142 20 Prague 4, Czech
Republic, e-mail: tmsoukup@biomed.cas.cz