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Dietary Zinc Deficiency Alters 5α-Reduction and Aromatization of Testosterone and Androgen and Estrogen Receptors in Rat Liver
Abstract
We studied the effects of zinc deficiency on hepatic androgen metabolism and aromatization, androgen and estrogen receptor binding, and circulating levels of reproductive hormones in freely fed, pair-fed and zinc deficient rats. Hepatic conversion of testosterone to dihydrotestosterone was significantly less, but formation of estradiol from testosterone was significantly greater in rats fed the zinc-deficient diet compared with freely fed and pair-fed control rats. There were significantly lower serum concentrations of luteinizing hormone, estradiol and testosterone in rats fed the zinc-deficient diet. No difference in the concentration of serum follicle-stimulating hormone was observed between the zinc-deficient group and either control group. Scatchard analyses of the receptor binding data showed a significantly higher level of estrogen receptor in zinc-deficient rats (36.6 +/- 3.4 fmol/mg protein) than in pair-fed controls (23.3 +/- 2.2 fmol/mg protein) and a significantly lower level of androgen binding sites in rats fed the zinc-deficient diet (6.7 +/- 0.7 fmol/mg protein) than in pair-fed control rats (11.3 +/- 1.2 fmol/mg protein). There were no differences in hepatic androgen and estrogen receptor levels between freely fed and pair-fed controls. These findings indicate that zinc deficiency reduces circulating luteinizing hormone and testosterone concentrations, alters hepatic steroid metabolism, and modifies sex steroid hormone receptor levels, thereby contributing to the pathogenesis of male reproductive dysfunction.
... It also plays a vital role in the synthesis, storage, crystallization, and secretion of insulin [20,21]. In addition, zinc plays an essential role in growth and reproduction in both males and females [22][23][24]. Zinc is involved in the synthesis and secretion of luteinizing hormone and folliclestimulating hormone, and it also plays an important role in gonadal differentiation, spermatogenesis, production of testicular steroid hormones, and androgen metabolism [23]. An animal experiment showed that a zinc-deficient diet significantly decreased the levels of serum zinc, plasma insulin, and serum testosterone in diabetic rats [25]. ...
... Many studies have shown that zinc is closely related to the female and male reproductive systems [23,24,46,47]. An in vitro study showed that zinc enhanced estradiol-induced responses dose-dependently, indicating that zinc could regulate estrogenic activity [48]. ...
... An in vitro study showed that zinc enhanced estradiol-induced responses dose-dependently, indicating that zinc could regulate estrogenic activity [48]. Zinc also regulates testosterone levels in men by participating in the production and secretion of luteinizing hormone, follicle-stimulating hormone, and prolactin, in turn [23,24]. In addition, experimental animal studies have shown that zinc status can influence sex hormone-induced responses [25,46]. ...
To explore the effects of CYP19A1 gene polymorphisms, plasma zinc, and urinary zinc levels and their interactions on type 2 diabetes mellitus (T2DM) in residents of Gongcheng County, Guangxi, China. The case–control study was used for the investing. The MassARRAY System was applied to genotype the CYP19A1 genes rs752760, rs10046, rs10459592, and rs700518 in 540 study subjects. Plasma and urinary zinc concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). Conditional logistic regression showed that rs752760 and plasma zinc were associated with T2DM risks with ORs of 0.593 (95% CI: 0.371–0.948) and 0.563 (95% CI: 0.356–0.889), respectively. Unconditional logistic regression analysis showed an association between urinary zinc levels and the risk of T2DM as well, with an OR of 0.352 (95% CI: 0.212–0.585). The results of the multiplicative interaction model showed that the rs752760 T allele was associated with a significantly reduced risk of T2DM with moderate/low plasma zinc levels, with ORs of 0.340 (95% CI: 0.161–0.715) and 0.583 (95% CI: 0.346–0.981), respectively, and the rs752760 T allele was also associated with a significantly decreased risk of T2DM with moderate/low urinary zinc levels, with ORs of 0.358 (95% CI: 0.201–0.635) and 0.321 (95% CI: 0.183–0.562), respectively. CYP19A1 rs752760 T allele and moderate/low plasma/urinary zinc levels reduce the risk of T2DM.
... Zinc deficiency disrupts the activity of angiotensin converting enzyme (ACE) which is involved in the production of adrenal androgens (Kwok et al., 2010) and this disruption results in reduced testosterone production and the inhibition of spermatogenesis (Bedwall and Bahuguna 1994). Zinc is required for the conversion of testosterone to its active form, dihydrotestosterone (Om and Chung 1996). The 5α-reductase enzyme that has a part in this conversion is a zinc-dependent enzyme (Om and Chung 1996). ...
... Zinc is required for the conversion of testosterone to its active form, dihydrotestosterone (Om and Chung 1996). The 5α-reductase enzyme that has a part in this conversion is a zinc-dependent enzyme (Om and Chung 1996). ...
... It is acknowledged that zinc deficiency suppressed the receptor activity of androgenic hormones and thus zinc had a critical part in the regulation of male reproductive functions (Om and Chung 1996). ...
Zinc is essential in the regulation of a variety of physiological and biochemical events in the organism. It plays a critical role in maintaining the cell membrane integrity, protein-carbohydrate-lipid metabolism, immune system, wound injury and in the regulation of a number of other biological processes associated with normal growth and development. Physiological and biochemical levels of many hormones are affected by zinc metabolism. Therefore, growth impairment, hypogonadism, and some endocrine diseases are associated with the deficiency of zinc. These effects of zinc are considered versatile. Zinc increases the synthesis of the growth hormone and its number of receptors; thus, it is an important mediator in the binding of this hormone to its receptor. Found in a large quantity in the pancreas tissue, zinc has a part in the regulation of the effect of insulin. Zinc is involved to much more thyroid hormone metabolism such as hormone synthesis, receptor activity, conversion of T4 to T3, and production of carrier proteins. The low levels of zinc and high levels of leptin in obese individuals point to a critical relationship between zinc and leptin. Zinc is related to enzyme activity to melatonin synthesis. Melatonin has regulatory activity for zinc absorption from gastrointestinal system. Zinc particularly affects the conversion of testosterone to dihydrotestosterone, as 5α-reductase that is involved in this conversion is a zinc-dependent enzyme. In consideration of these relations, zinc is accepted to play critical roles in the endocrine system. The aim of the current review is to draw attention to the effects of zinc on the endocrine system.
... Zinc has been shown to regulate genes participating in steroidogenesis. The role of Zn in regulating androgen metabolism and aromatization has been shown [41][42][43]. One study found decreased estradiol and LH serum levels, as well as decreased androgen receptors and increased estrogen receptors in livers from rats with a Zn deficient diet [41]. ...
... The role of Zn in regulating androgen metabolism and aromatization has been shown [41][42][43]. One study found decreased estradiol and LH serum levels, as well as decreased androgen receptors and increased estrogen receptors in livers from rats with a Zn deficient diet [41]. Another study using zebra fish embryos as models found that Zn supplement induces the expression of Cyp19a1 after cadmium inhibitory effects [42]. ...
The use of zinc oxide nanoparticles (ZnO NP) in consumer products is increasing, raising concern about their potential toxicity to human health. Nanoparticles have endocrine disrupting effects and can induce oxidative stress, leading to biomolecule oxidation and cell dysfunction. The ovary is one of the most important endocrine organs in female reproduction. Nanoparticles accumulate in the ovary, but it is unknown whether and how exposure to these materials disrupts antral follicle functions. Thus, this study tested the hypothesis that the in vitro exposure to ZnO NPs affects the steroidogenic pathway and induces oxidative stress in ovarian antral follicles. Antral follicles from CD-1 mice were cultured with ZnO NPs (5, 10, and 15 µg/mL) for 96 h. ZnO NP exposure did not affect apoptosis and cell cycle regulators at any of the tested concentrations. ZnO NP exposure at low levels (5 µg/mL) increased aromatase levels, leading to increased estradiol levels and decreased estrogen receptor alpha (Esr1) expression. ZnO NP exposure at 15 µg/mL induced an antioxidant response in the antral follicles as evidenced by changes in expression of antioxidant molecules (Nrf2, Cat, Sod1, Gsr, Gpx) and decreased levels of reactive oxygen species. Interestingly, ZnO NPs dissolve up to 50% in media and are internalized in cells as soon as 1 h after culture. In conclusion, ZnO NPs are internalized in antral follicles, leading to increased estrogen production and an antioxidant response.
... A similar type of result was also reported by Nishi, in 1996 where hypogonadism led by Zn deficient diet was recorded [35] . Om and Chung (1996) showed that zinc deficiency led to inhibition in LH and estrogen levels [36] . Nonetheless, a remarkable finding supporting the relation between zinc and estrogen was that zinc was a significant stimulator in estradiol synthesis [37] . ...
... A similar type of result was also reported by Nishi, in 1996 where hypogonadism led by Zn deficient diet was recorded [35] . Om and Chung (1996) showed that zinc deficiency led to inhibition in LH and estrogen levels [36] . Nonetheless, a remarkable finding supporting the relation between zinc and estrogen was that zinc was a significant stimulator in estradiol synthesis [37] . ...
The seed cycling/seed rotation diet is a new trend that claims to be effective for female menstrual dysfunctions such as irregular menstruation, menstrual cramps, infertility, menopausal symptoms (hot flashes, fatigue, etc.), and PCOS. The higher prevalence of hormonal imbalance in women is a contributing factor to all of these menstrual dysfunctions. The major hormones that control menstruation in females include progesterone, estrogen, luteinizing hormone (LH), and follicular stimulating hormone (FSH), and a simple imbalance in their concentration is the root cause of a variety of menstrual problems. The practice of eating specific seeds during the two main phases of the menstrual cycle (follicular and luteal) to promote a healthy balance of estrogen and progesterone levels in women is known as the seed rotation diet. During the follicular stage consumption of pumpkin seed and flax seed is advised and in the luteal stage consumption of sunflower seed and sesame seed is advised in this diet. Recent studies have shown that pumpkin seeds are rich in phytoestrogen which is a polyphenol compound that exerts a mammalian estrogenic-like effect in body. Similarly, flax seed in the first phase helps to bind the excess estrogen produced to maintain the hormonal homeostasis. Sesame seeds, which are high in zinc and lignans, are thought to help with progesterone balance during the luteal phase, while sunflower seeds, which are high in vitamin E and selenium aids in, increasing progesterone production and liver detoxification of excess estrogen. However, despite plenty of anecdotal accounts of its usefulness, scientific evidence to back its claims is still weak or lacking.
... The physiological role of zinc regarding testosterone biology is related to its requirement in the synthesis and secretion of LH. As previously discussed, LH stimulates testosterone synthesis in the Leydig cells [6,14,144]. Zinc is also important in the conversion of testosterone to DHT [144]. ...
... As previously discussed, LH stimulates testosterone synthesis in the Leydig cells [6,14,144]. Zinc is also important in the conversion of testosterone to DHT [144]. DHT is converted from testosterone by the enzyme 5α-reductase in the cytoplasm of the cell. ...
Elevations in the circulating concentration of androgens are thought to have a positive effect on the anabolic processes leading to improved athletic performance. Anabolic-androgenic steroids have often been used by competitive athletes to augment this effect. Although there has been concerted effort on examining how manipulating training variables (e.g., intensity and volume of training) can influence the androgen response to exercise, there has been much less effort directed at understanding how changes in both macronutrient and micronutrient intake can impact the androgen response. Thus, the focus of this review is to examine the effect that manipulating energy and nutrient intake has on circulating concentrations of testosterone and what the potential mechanism is governing these changes.
... On the other hand, some animal studies demonstrated a possible androgenic effect of zinc. According to a study, when rats were fed with a zinc-deficient diet, their serum LH and testosterone levels were decreased, and the zincdeficient diet caused a reduction in androgen binding sites [37]. Similarly, 20-week dietary zinc restriction in healthy men led to significant decrease in serum testosterone levels [38]. ...
... Zinc was also shown to inhibit the transformation of testosterone to DHT at high tissue concentrations in human skin [5]. On the other hand, in rats fed with zinc-deficient diet, formation of DHT from testosterone was significantly lower [37]. Similarly, zinc supplementation increased the DHT levels in infertile men [46]. ...
Zinc has shown to have an anti-androgenic effect through 5 alpha-reductase enzyme activity inhibition in skin. However, there are contradicting findings concerning the effect of zinc on hirsutism mainly from studies including adult women with polycystic ovary syndrome (PCOS). The aim of our study was to investigate the association between serum zinc levels and hirsutism in adolescents. Between October 2017 and June 2018, 51 female adolescents with hirsutism (mean age: 16.11 ± 1.47 years) and 51 healthy female controls were included in the study (mean age: 15.5 ± 1.40 years). Adolescents with hirsutism were classified under two groups; PCOS (n = 34, 66.7%) and idiopathic causes of hirsutism (idiopathic hirsutism (n = 9, 17.6%) and idiopathic hyperandrogenemia (n = 8, 15.7%)). The serum zinc levels were measured via atomic absorption spectrophotometry. The mean zinc levels of adolescents with hirsutism (102.02 ± 11.64 μg/dl) and the control group (101.72 ± 16.71 μg/dl) were similar (p = 0.915). Additionally, there was no significant difference among the mean zinc levels of the hirsutism sub-groups and the control group (p = 0.979). While some studies demonstrated low zinc levels in women with hirsutism, some studies similar to ours showed no association. Adolescence is a developmental phase where generally isolated mild hirsutism is not associated with hyperandrogenism and more studies are needed to evaluate the effect of zinc on hirsutism in this age group.
... Hannas et al. (2011Hannas et al. ( , 2012 showed that PEs exposure could inhibit the expression of StAR, CYP11, P450scc, 17b-HSD, CYP17 and 3b-HSD. Om and Chung (1996) reported that dietary zinc deficiency altered 5a-reduction and aromatization of testosterone. Nuttall et al. (2017) reported that maternal marginal zinc deficiency enhanced aromatization activity of androgen in maternal and fetal tissues and altered steroid metabolism in rats. ...
... That is, PIWI proteins were the candidate for male reproductive function. In vitro and in vivo studies showed that estrogen could down-regulate the expression of MIWI (PIWIL1) and MILI (PIWIL2) in male testis (Pan et al., 2012). Estrogen also regulated Piwi expression during Xenopus embryogenesis and early larval development (Zhang et al., 2010). ...
... The latter could have a significant impact on fetal steroid homeostasis. In previous studies both phthalate exposure and zinc deficiency disrupted testosterone and estrogen signaling and disproportionately affected development in male rats compared with females (Andrade et al., 2006;Blystone et al., 2010;Om and Chung, 1996;Swenerton and Hurley, 1968). Increased GC signaling has also been implicated independently in the developmental defects resulting from phthalate exposure (Cooper et al., 2008;Xiao-feng et al., 2009) and zinc deficiency (DePasquale-Jardieu and Fraker, 1979;Takeda et al., 2007). ...
... These results suggest a higher androgen aromatization activity as a consequence of zinc deficiency. This is in agreement with previous observations of low testosterone and high estradiol concentrations in the liver of male adult rats fed a severe zinc deficient diet for 3 months (Om and Chung, 1996). Interestingly, MZ had an opposite effect on maternal liver estradiol levels in dams exposed to DEHP, and the testosterone to estradiol ratio was correlated with MEHP in maternal plasma. ...
Disruption of steroid hormone signaling has been implicated independently in the
developmental abnormalities resulting from maternal phthalate plasticizer exposure and
developmental zinc deficiency. This study investigated if secondary zinc deficiency may result
from dietary exposure to a low level of DEHP through gestation and if this could be associated
with altered steroid metabolism. The interaction between marginal zinc nutrition and DEHP
exposure to affect pregnancy outcome, zinc status, and steroid metabolism was also assessed. For
this purpose, rats were fed a diet containing an adequate (25 mg/kg) or marginal (10 mg/kg) level
of zinc without or with DEHP (300 mg/kg) from gestation day (GD) 0 until GD 19. Steroid
profiles were measured in dam liver, plasma, adrenal glands, and in fetal liver by UPLC/MS-MS.
In dams fed the adequate zinc diet, DEHP exposure decreased maternal weight gain and led to
hepatic acute-phase response and zinc accumulation. The latter could compromise zinc
availability to the fetus. DEHP and marginal zinc deficiency caused several adverse effects on
the maternal and fetal steroid profiles. Interactions between DEHP exposure and marginal zinc
deficient nutrition affected 17OH pregnenolone and corticosterone, while pregnenolone levels
were specifically affected by DEHP exposure. Maternal marginal zinc deficiency specifically
affected maternal progesterone and aldosterone, and presented evidence of increased androgen
aromatization activity in maternal and fetal tissues. Results stress the potential major impact of
mild DEHP exposure on maternal/fetal steroid metabolism that can be potentiated by nutritional
and chronic disease states leading to zinc deficiency.
... Studies in animal models as well as clinical studies have demonstrated that hypogonadism is a prominent feature of Zn deficiency in humans and animals (37,38); however, the underlying mechanisms responsible for these endocrine effects observed in Zn deficiency remain unclear. The present study has reported a significant decrease in serum testosterone levels and Zn concentrations in the testis and Leydig cells of mice, which is in line with the findings of previous studies on a number of male mammal species (37)(38)(39)(40). In addition, ZnT7 was prinicipally expressed and colocalized with StAR in the Leydig cells of male CD-1 mice. ...
... Several studies have demonstrated that ZnT7 is located in the Golgi apparatus and may participate in the transport of cytoplasmic Zn into the Golgi apparatus (21,47). ZnT7-deficient rats had lower levels of Zn in their cells and tissues, a reduced food intake, and poor growth; all of which are clinical manifestations of Zn deficiency (39). In the present study, double immunofluorescence staining revealed the colocalization of ZnT7 and StAR in the mouse Leydig cells. ...
Previous studies have demonstrated that zinc (Zn) is an essential trace element which is involved in male reproduction. The zinc transporter (ZnT) family, SLC30a, is involved in the maintenance of Zn homeostasis and in mediating intracellular signaling events; however, relatively little is known regarding the effect of ZnTs on testosterone synthesis. Thus, in the present study, we aimed to determine the effect of Zn transporter 7 (ZnT7) on testosterone synthesis in male CD-1 mice and mouse Leydig cells. The findings of the present study revealed that the concentrations of Zn in the testes and Leydig cells were significantly lower in mice fed a Zn-deficient diet compared with the control mice fed a Zn-adequate diet. In addition, ZnT7 was principally expressed and colocalized with steroidogenic acute regulatory protein (StAR) in the Leydig cells of male CD-1 mice. ZnT7 expression was downregulated in the mice fed a Zn-deficient diet, which led to decreases in the expression of the enzymes involved in testosterone synthesis namely cholesterol side chain cleavage enzyme (P450scc) and 3hydroxysteroid dehydrogenase/D5-D4 isomerase (3HSD) as well as decreased serum testosterone levels. These results suggested that Znt7 may be involved in testosterone synthesis in the mouse testes. To examine this hypothesis, we used the mouse Leydig tumor cell line (MLTC-1 cell line) in which the ZnT7 gene had been silenced, in order to gauge the impact of changes in ZnT7 expression on testosterone secretion and the enzymes involved in testosterone synthesis. The results demonstrated that ZnT7 gene silencing downregulated the expression of StAR, P450scc and 3HSD as well as progesterone concentrations in the human chorionic gonadotrophin (hCG)-stimulated MLTC-1 cells. Taken together, these findings reveal that ZnT7 may play an important role in the regulation of testosterone synthesis by modulating steroidogenic enzymes, and may represent a therapeutic target in testosterone deficiency.
... In addition, data indicate that the zinc content of the brain might also show gender differences (Lee et al., 2002) and male and female offspring from prenatal zinc deficient mice might be differentially affected. For example, zinc deficiency may alter maternal testosterone levels (Om and Chung, 1996) due to excessive conversion of testosterone into estrogen by an aromatase that is normally inhibited by zinc. ...
... For example, developing testes are more active than ovaries, resulting in higher levels of circulating testosterone and estradiol in male than in female fetuses. Conversion of testosterone to estrogen is mediated by a zinc dependent aromatase that is inhibited by zinc (Om and Chung, 1996). Under zinc deficient conditions, disinhibition might promote the conversion and thus lower testosterone levels, which might affect female and male pups differently. ...
Zinc deficiency has recently been linked to the etiology of autism spectrum disorders (ASD) as environmental risk factor. With an estimated 17% of the world population being at risk of zinc deficiency, especially zinc deficiency during pregnancy might be a common occurrence, also in industrialized nations. On molecular level, zinc deficiency has been shown to affect a signaling pathway at glutamatergic synapses that has previously been identified through genetic mutations in ASD patients, the Neurexin-Neuroligin-Shank pathway, via altering zinc binding Shank family members. In particular, prenatal zinc deficient but not acute zinc deficient animals have been reported to display autism like behavior in some behavioral tests. However, a full behavioral analysis of a possible autism like behavior has been lacking so far. Here, we performed an extensive behavioral phenotyping of mice born from mothers with mild zinc deficiency during all trimesters of pregnancy. Prenatal zinc deficient animals were investigated as adults and gender differences were assessed. Our results show that prenatal zinc deficient mice display increased anxiety, deficits in nest building and various social interaction paradigm, as well as mild alterations in ultrasonic vocalizations. A gender specific analysis revealed only few sex specific differences. Taken together, given that similar behavioral abnormalities as reported here are frequently observed in ASD mouse models, we conclude that prenatal zinc deficient animals even without specific genetic susceptibility for ASD, already show some features of ASD like behavior.
... Zinc is an essential metal required in adequate amounts for brain development and function [40], growth and development [41], immune function, and bodily defense [42], as well as for overall body regulation [43]. The high concentration of Zn found in smoked catfish from the Olomore market indicates a potential risk of Zn toxicity, which may lead to health issues such as immune suppression [44] and hormonal disorders [45]. ...
Fish is a significant source of animal protein for humans; however, it has a tendency to bioaccumulate toxicants from the environment. The present study assessed the health risks associated with potential toxic metals (PTMs) in differently processed catfish (Clarias gariepinus) from four markets in Abeokuta metropolis, southwestern Nigeria. A total of 60 samples were collected and analyzed for PTMs using an Atomic Absorption Spectrophotometer. The health risk assessment was evaluated based on the hazard quotient (HQ), hazard index (HI), and cancer risk (CR). Iron concentrations ranged from 8.10 ± 6.80 to 70.7 ± 30.8 mg/kg, making it the highest measured metal in the fish samples. The mean chromium (Cr) levels (0.25 ± 0.25 to 28.4 ± 14.5 mg/kg), and lead concentrations (< 0.08 to 0.80 ± 0.70 mg/kg) exceeded the permissible limits set by the joint FAO/WHO, in most of the differently processed fish samples. Principal component analysis identified two likely sources of metal contamination in the fish samples as pond/river runoff and vehicular emissions. The health risk assessment revealed a HQ for Cr exceeding the permissible limit of 1.0 across all processed catfish consumed by both adults and children. Similarly, the CR values for Cr surpassed the threshold of 1.0 × 10⁻4 in both age groups. Chromium accounted for 43% to 98% of the contributions to both carcinogenic and non-carcinogenic health risks. The findings indicated that children are more susceptible to the adverse health effects of PTMs than adults through the consumption of variously processed catfish.
... Research has indicated that alterations in the enzymatic conversion of testosterone are the primary cause of the decrease in testosterone levels observed in Zn deficiency [42]. More specifically, Zn-deficient Leydig cells are able to take in cholesterol and neutral lipids but are unable to transform them into sex hormones [44]. This finding suggests that Zn deficiency may decrease the expression of important steroidogenic enzymes in the testis, such as 3β-Hydroxysteroid-Dehydrogenase (3β-HSD), cholesterol side-chain cleavage (P450scc), and Steroidogenic acute regulatory (StAR) as proven previously [45]. ...
Research into innovative non-pharmacological therapeutic routes via the utilization of natural elements like zinc (Zn) has been motivated by the discovery of new severe acute respiratory syndrome-related coronavirus 2 (SARS-COV2) variants and the ineffectiveness of certain vaccination treatments during COVID-19 pandemic. In addition, research on SARS-COV-2’s viral cellular entry and infection mechanism has shown that it may seriously harm reproductive system cells and impair testicular function in young men and adolescents, which may lead to male infertility over time. In this context, we conducted a narrative review to give an overview of the data pertaining to Zn’s critical role in testicular tissue, the therapeutic use of such micronutrients to enhance male fertility, as well as in the potential mitigation of COVID-19, with the ultimate goal of elucidating the hypothesis of the potential use of Zn supplements to prevent the possible harmful effects of SARS-COV2 infection on testis physiological function, and subsequently, on male fertility.
... Zinc is crucial for corpus luteum formation, supporting progesterone production essential for implantation [44]. Studies link zinc supplementation to elevated progesterone, while deficiency inhibits LH and estrogen, impacting luteal function [45][46][47][48]. Zinc supplementation is linked to enhanced lipid and glucose metabolism [32]. ...
This chapter aims to provide a comprehensive guide to optimizing nutrition for the management of polycystic ovary syndrome (PCOS), a hormonal disorder affecting reproductive-aged women that are associated with various metabolic and reproductive complications. It explores the critical role of nutrition in PCOS management, focusing on evidence-based dietary strategies to alleviate symptoms, promote hormonal balance, and enhance overall health outcomes. Beginning with the pathophysiology of PCOS, the chapter highlights the impact of insulin resistance, inflammation, and hormonal imbalances on the condition. The chapter provides practical guidelines for optimizing macronutrient intake, including recommendations for carbohydrate quality, protein sources, and fat composition. Additionally, it explores the potential benefits of dietary supplements and herbal remedies in PCOS management. It addresses key lifestyle factors—physical activity, stress management, and adequate sleep—which synergistically enhance nutrition in optimizing PCOS management. This valuable resource is tailored for healthcare professionals, nutritionists, and individuals with PCOS seeking evidence-based guidance on effectively managing this complex condition through optimized nutrition.
... In general, Zn was reported to improve male sperm quality and is essential for the female reproductive system including embryogenesis and development (44). It is reported that Zn deficiency affected the reproductive function of rats (45,46). In agreement with the results obtained by Favero et al. (47), we can detect some difference in egg fertility and hatchability between FIGURE 1 | Effects of dietary Zn-MHA supplementation on the mRNA relative expressions of reproductive axis genes in broiler breeders. ...
Inorganic zinc (Zn) supplements are commonly used in poultry feeds, but their low utilization results in the increase of Zn excretion. Thus, to provide a new perspective for the substitution of inorganic Zn, a novel Zn methionine hydroxy analog chelate (Zn-MHA) was studied in the present study to evaluate its effects on laying performance, serum hormone indexes and reproductive axis-related genes in broilers breeders. A total of 480 Hubbard breeders (56-week-old) were fed a basal diet (containing 27.81 mg Zn/kg) without Zn addition for 2 weeks, and then allocated to 4 groups with 6 replicates (each replicate consisting of 10 cages and 2 breeders per cage) for 10 weeks. Four treatment diets given to broiler breeders included the basal diet added with 25, 50, and 75 mg/kg of Zn-MHA and 100 mg/kg of Zn sulfate (ZnSO4). The laying rate, egg weight and feed conversation ratio increased in the 75 mg/kg Zn-MHA group compared to the ZnSO4 group. The eggshell thickness was not decreased with the addition of 50 mg/kg and 75 mg/kg Zn-MHA in the diet compared to the 100 mg/kg ZnSO4 group. There was a significant improvement in the reproductive performance of breeders in the 75 mg/kg Zn-MHA group, including the fertility and 1-day-old offspring weight. Besides, serum sex hormone levels including FSH and P4 increased significantly in 75 mg/kg Zn-MHA group. No significant effect on the ovarian weight or the number of follicles in broiler breeders was observed by supplementing Zn-MHA. Compared to the 100 mg/kg ZnSO4 group, dietary supplementation with 75 mg/kg of Zn-MHA showed an up-regulation of the FSHR mRNA in the granular layer of follicles. However, dietary supplementation of Zn-MHA had no effects on mRNA expressions of the ovarian LHR and PRLR genes. These findings reinforce the suggestion that Zn-MHA (75 mg/kg) could replace ZnSO4 (100 mg/kg) as a Zn supplement in diet of broiler breeders, which resulted in better laying and reproduction performances by regulating the expression levels of reproductive axis related genes and serum hormone levels.
... For people with BPH, zinc levels in plasma and prostate tissue tend to decline, in contrast to prostatitis. Zinc has shown the ability to alleviate lower urinary tract symptoms (LUTS), possibly because it can inhibit 5-alpha-reductase and/or prolactin (Li et al. 2005;Gómez et al. 2007;Om and Chung 1996;Login, Thorner, and MacLeod 1983). Prolactin has been shown to enhance testosterone secretion by the prostate, thereby supplying more substrate, leading to increased dihydrotestosterone (DHT). ...
Prostate disorders are commonplace in medicine, especially in older men, with prostatitis, benign prostatic hyperplasia, and prostate cancer being the most abundant pathologies. The complexity of this organ, however, turns treatment into a challenge. In this review, we aim to provide insight into the efficacy of alternative treatments, which are not normally used in conventional medicine, with a particular focus on nutrients. In order to understand why and how nutrition can be beneficial in diseases of the prostate, we give an overview of the known characteristics and features of this organ. Then, we provide a summary of the most prevalent prostate illnesses. Finally, we propose nutrition-based treatment in each of these prostate problems, based on in-depth research concerning its effects in this context, with an emphasis on surgery. Overall, we plead for an upgrade of this form of alternative treatment to a fully recognized mode of therapy for the prostate.
... These finding confirmed the oxidant effect of estrogen deprivation which leads to the alteration of membrane integrity and proteins in cells [69]. Furthermore, this steroid is known by its antioxidant properties; hence, failure in its production results in oxidative stress generation [70]. ...
Postmenopausal women express great failure in their ovarian hormone production, especially estrogen. This deficiency may promote hypercholesterolemia and accelerate the redox imbalance. The present study was designed to evaluate the protective effect of Avena sativa against estrogen deficiency-induced liver and uterus oxidative injury in experimental ovariectomized mice. Female mice were randomly divided into five groups: group one (negative control) received normal diet and distilled water (C), group two (positive control) received daily enriched diet with oat grains and was kept on tap distilled water at a dose of 200 mg kg-1 d-1 (A), group three (ovariectomized mice) was nontreated fed with normal diet (O), group four includes ovariectomized mice treated daily with estradiol given by intraperitoneal injection at a dose of 100 μg kg-1 d-1 (OE), and the fifth group also includes ovariectomized mice which received enriched diet with oat grain parts with the same dose given to group two. The treatment period lasted two consecutive months. Both oat and hormonal treatments of ovariectomized groups resulted in a significant reduction in triglycerides and total cholesterol and increased high-density lipoprotein (HDL) levels in the plasma after 21 and 60 days of treatment. Besides, the coadministration of A. sativa has decreased the activities of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) and increased transaminase activities after 21 and 60 days of treatment. On the other hand, this cereal has restored the enzymatic (SOD, CAT, and GPx) and nonenzymatic antioxidant activities (GSH) as well as the elevated thiobarbituric acid reactive substances (AOPP and PCO) to near-normal values. The beneficial effects of this cereal were confirmed by a histological study of the liver and uterus of all previous cited groups. Our finding emphasized the antioxidant and antilipidemic effect of oat grain part, suggesting the use of this cereal in the prevention of liver and uterus diseases that occurred in postmenopausal women.
... Oestrogen also induces anti-inflammatory effector functions in immunoglobulin G (IgG) by inducing β-galactoside α-2,6-sialyltransferase (1St6Gal1) expression in antibody-producing cells and by increasing immunoglobulin Fc fragment sialylation in mice and in patients with RA [80]. Zinc deficiency can alter androgen and oestrogen receptor levels while it impairs the synthesis/secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) [81]. On the other hand, zinc supplementation in ovariectomized rats increases serum oestrogen and progesterone levels [82]. ...
Osteoarthritis (OA) and rheumatoid arthritis (RA) are inflammatory articular conditions with different aetiology, but both result in joint damage. The nutritionally essential metal zinc (Zn2+) and the non-essential metal cadmium (Cd2+) have roles in these arthritic diseases as effectors of the immune system, inflammation, and metabolism. Despite both metal ions being redox-inert in biology, they affect the redox balance. It has been known for decades that zinc decreases in the blood of RA patients. It is largely unknown, however, whether this change is only a manifestation of an acute phase response in inflammation or relates to altered availability of zinc in tissues and consequently requires changes of zinc in the diet. As a cofactor in over 3000 human proteins and as a signaling ion, zinc affects many pathways relevant for arthritic disease. How it affects the diseases is not just a question of zinc status, but also an issue of mutations in the many proteins that maintain cellular zinc homoeostasis, such as zinc transporters of the ZIP (Zrt-/Irt-like protein) and ZnT families and metallothioneins, and the multiple pathways that change the expression of these proteins. Cadmium interferes with zinc’s functions and there is increased uptake under zinc deficiency. Remarkably, cadmium exposure through inhalation is now recognized in the activation of macrophages to a pro-inflammatory state and suggested as a trigger of a specific form of nodular RA. Here, we discuss how these metal ions participate in the genetic, metabolic, and environmental factors that lead to joint destruction. We conclude that both metal ions should be monitored routinely in arthritic disease and that there is untapped potential for prognosis and treatment.
... However, there is very little data on how Zn influences the expression/concentration of AR. Zn-deficient rats display decreased concentrations of AR in prostatic and hepatic cells, and decreased levels of DHT, T and LH in serum [32,33]. Although practically no data exists on AR expression following Zn administration, the opposite effect (an increase of AR protein expression) could be expected. ...
Background:
Zinc (Zn) and selenium (Se) play a well-documented role in cancer prevention (e.g., for prostate cancer), and their combined supplementation is often given as a recommended prophylactic agent. The aim of the study was to determine the influence of Zn and/or Se supplementation on the androgen receptor (AR) in the prostate lobes and the serum selected hormone concentrations; a hitherto unresearched topic.
Methods:
Male rats (n = 84) were administered with Zn and/or Se intragastrically for up to 90 days. The effects of administration on the tested parameters were checked after 30 and 90 days of administration and additionally, 90 days after the end of 90 day administration.
Results:
Zn alone leads to an increase in serum testosterone concentrations, while the protein expression of AR in both parts of the prostate increases. Combined administration of Zn and Se eliminates the effect of Zn, which may suggest that these two elements act antagonistically. Se supplementation alone results in the same level of AR protein expression in administration and 90 days after administration periods.
Conclusion:
This paper presents the first report of the influence of Zn and/or Se supplementation on the protein expression of AR in the prostate. Our findings seem to indicate that simultaneous supplementation of both elements may be ineffective.
... Vitamin D may increase testosterone levels. Male with vitamin D levels of 30 ng / ml in the blood, testosterone levels are very significantly higher than the levels of vitamin D in the blood of less than 30 ng / ml [4] The vitamin D content of moringa leaves in this study were able to increase testosterone Ref. [5] states that at 12 -week old male rats which were fed for six weeks of Zn deficiency, increased the levels of FSH and LH. The decrease of LH caused an impaired in testosterone secretion that resulted in low levels of testosterone. ...
Rabbit is an alternative livestock that have a chance of being the source of healthy and high quality animal protein. One way to improve the productivity of rabbit meat is to improve the quality of male rabbits. Moringa leaves have androgenic effects by increasing testosterone, increasing blood flow to the male reproductive organs and stimulating the central nervous system to increase libido. The aims of this study were to find out the effects of moringa leaf meal substitution in commercial feed on the testosterone levels and mating capability of male rabbits. Twenty four of four months old male rabbits with an average live weight of 1200g were used in this study. There were four treatments in this study including 0% (K0) as control and 15% (K1), 30% (K2), 45% (K3) substitution of moringa leaf meal in commercial feed and each treatment consisted of six replicates. The treatments were carried out for two months. The variables measured were mating capability and testosterone levels in the blood. The results showed that there were significant differences (P <0.05) between all treatments (K1, K2, K3) and the control (K0). Substitution of commercial feed with moringa leaf meal in this study was able to increase the testosterone levels in the blood and mating capability of male rabbits. It was concluded that the moringa leaf meal able to substitute the commercial feed up to 45 % to improve the testosterone levels in the blood and mating capability of male rabbits. To get maximum the testosterone levels in the blood and mating capability of male rabbits it should be better substituted the commercial feed with moringa leaf meal as much as 35.07%
... Wilborn et al. [416] had resistance trained males ingest a ZMA supplement or placebo in a double-blind fashion and resistance train for 8 weeks and found no change in free or total testosterone, strength or fat-free mass (via DXA). It is noted that previous deficiencies in zinc may negatively impact endogenous production of testosterone secondary to its role in androgen metabolism and steroid receptor interaction [417]. To this point, Brilla and Conte [414] did report depletions of both zinc and magnesium, thus increases in testosterone levels could have been attributed to deificient nutritional status rather than a pharmacologic effect. ...
Background:
Sports nutrition is a constantly evolving field with hundreds of research papers published annually. In the year 2017 alone, 2082 articles were published under the key words 'sport nutrition'. Consequently, staying current with the relevant literature is often difficult.
Methods:
This paper is an ongoing update of the sports nutrition review article originally published as the lead paper to launch the Journal of the International Society of Sports Nutrition in 2004 and updated in 2010. It presents a well-referenced overview of the current state of the science related to optimization of training and performance enhancement through exercise training and nutrition. Notably, due to the accelerated pace and size at which the literature base in this research area grows, the topics discussed will focus on muscle hypertrophy and performance enhancement. As such, this paper provides an overview of: 1.) How ergogenic aids and dietary supplements are defined in terms of governmental regulation and oversight; 2.) How dietary supplements are legally regulated in the United States; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of nutritional approaches to augment skeletal muscle hypertrophy and the potential ergogenic value of various dietary and supplemental approaches.
Conclusions:
This updated review is to provide ISSN members and individuals interested in sports nutrition with information that can be implemented in educational, research or practical settings and serve as a foundational basis for determining the efficacy and safety of many common sport nutrition products and their ingredients.
... This may be due to the fact that only data for older (pre-vasectomy) controls were available as reference. Nevertheless, zinc plays an important role for the immune system [36] and dietary zinc also has the potential to alter steroid hormone turnover and modulate testosterone aromatization [37]. Moreover, BPH and PCa tissues also have significantly reduced zinc levels compared to normal prostate tissue [38]. ...
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is associated with urinary tract symptoms and hormonal imbalances amongst others. The heterogeneous clinical presentation, unexplored molecular background and lack of prostate biopsies complicate therapy. Here, using liquid biopsies, we performed a comprehensive translational study on men diagnosed with CP/CPPS type III (n
=
50; median age 39.8, range 23-65) and age-matched controls (n
=
61; median age 36.8, range 20-69), considering biochemical parameters of blood and ejaculates, and epigenetic regulation of the estrogen receptor genes (ESR1 and ESR2) in leukocytes isolated from blood (systemic regulation) and in somatic cells isolated from ejaculates (local regulation). We found elevated 17β-estradiol (E2) levels in seminal plasma, but not in blood plasma, that was significantly associated with CP/CPPS and impaired urinary tract symptoms. In ejaculated somatic cells of CP/CPPS patients we found that ESR1 and ESR2 were both significantly higher methylated in CpG-promoters and expressionally down-regulated in comparison to controls. Mast cells are reported to contribute to CP/CPPS and are estrogen responsive. Consistent with this, we found that E2 -treatment of human mast cell lines (HMC-1 and LAD2) resulted in altered cytokine and chemokine expression. Interestingly, in HMC-1 cells, possessing epigenetically inactivated ESR1 and ESR2, E2 -treatment led to a reduced transcription of a number of inflammatory genes. Overall, these data suggest that elevated local E2 levels associate with an epigenetic down-regulation of the estrogen receptors and have a prominent role in CP/CPPS. Investigating E2 levels in semen could therefore serve as a promising biomarker to select patients for estrogen targeted therapy.
... An involvement of zinc in the regulation of sex hormones can be concluded indirectly, as several alterations that can occur during pregnancy upon zinc deficiency. Zinc deficiency also alters testosterone levels and modifies sex steroid hormone receptor levels (Om and Chung 1996) (Table 2). The nuclear receptor for sex steroid contains zinc fingers motif in their protein structure that might explain zinc dependency of these hormonal systems (Sauer et al. 2016). ...
... The discrepancies concerning the two aforementioned studies may be explained by deficiencies of these minerals. Due to the role that zinc deficiency plays relative to androgen metabolism and interaction with steroid receptors [150], when there are deficiencies of this mineral, testosterone production may suffer. In the study showing increases in testosterone levels [148], there were depletions of zinc and magnesium in the placebo group over the duration of the study. ...
Abstract Sport nutrition is a constantly evolving field with literally thousands of research papers published annually. For this reason, keeping up to date with the literature is often difficult. This paper presents a well-referenced overview of the current state of the science related to how to optimize training through nutrition. More specifically, this article discusses: 1.) how to evaluate the scientific merit of nutritional supplements; 2.) general nutritional strategies to optimize performance and enhance recovery; and, 3.) our current understanding of the available science behind weight gain, weight loss, and performance enhancement supplements. Our hope is that ISSN members find this review useful in their daily practice and consultation with their clients.
... Moreover, the nuclear receptors for sex steroids contain zinc finger motifs in their protein structure that might explain zinc dependency of these hormonal systems. In addition, zinc deficiency alters testosterone levels and modifies sex steroid hormone receptor levels [22]. ...
Zinc is an essential trace element for humans and plays a critical role both as a structural component of proteins and as a cofactor in about 300 enzymes. Zinc deficiency was, for example, reported to affect the immune response and the endocrine system and to induce and modify brain disorders. Besides hereditary zinc deficiency, zinc deficiency – at least in mild forms – is nowadays a very abundant health issue. Today, an estimated 20% of the population worldwide is at risk of developing zinc deficiency with a high number also in industrialized countries. The major risk factors to develop zinc deficiency in industrialized nations are aging and pregnancy. Mechanistic and behavioral studies on the effects of zinc deficiency have mainly been performed using animal models. However, in combination with the few studies on human subjects, a picture emerges that shows importance of adequate nutritional zinc supply for many processes in the body. Especially the immune system and brain development and function seem to be highly sensitive to zinc deficiency. Here, we provide an overview on the effects of zinc deficiency on different organ systems, biological processes, and the associations of zinc deficiency with pathologies observed in humans and animal models.
... Has antiphosphodiesterase activity (Bombardelli, 2006) Visnagin A. visnaga (Duarte et al., 1999) Weakly inhibited the hydrolytic activity of PDE5 (Duarte et al., 1999) Withanolides W. somnifera (Mishra, Singh, & Dagenais, 2000) The Methanolic Extract of W. somnifera acted on GABA A receptors in gonadotropin-releasing hormone (GnRH) neurons in mice (Bhattarai, Park, & Han, 2010) Zinc A. vera contains 12.6 μg/kg (Manish, 2013) Zinc-deficient rats had lower serum concentrations of testosterone & LH but not FSH than control groups (Om & Chung, 1996) A. herba alba contains 45.1 μg/kg (Manish, 2013) During zinc deficiency, retarded development of testicular growth involved marked atrophy of tubular epithelium. Zinc deficiency decreases output of pituitary gonadotrophins and androgen production (Hidiroglou & Knipfel, 1984) C. sativum contains 51.6 μg/kg (Manish, 2013) F. vulgare contains 37.5 μg/kg (Manish, 2013) Hemidesmus indicus contains 29.4 μg/kg (Manish, 2013) L. sativum contains 77 μg/kg (Manish, 2013) Peganum harmala contains 20.5 μg/kg (Manish, 2013) W. somnifera contains 43.01 μg/kg (Manish, 2013) D. carota contains 3.2 mg/100 g (Singh, Kawatra, & Sehgal, 2001) PDE5, phosphodiesterase type 5. ...
Male sexual dysfunction is a serious problem which has an impact on the quality of life. In Jordanian folk medicine, 56 plant species were reported to be used by males to improve sexual potency and as aphrodisiacs. The aim of this study was to search for scientific evidence justifying their folk use. Of the 15 studied plants, only five were found to enhance spermatogenesis. The other 10 were reported to decrease spermatogenesis at least by one study. The majority of the studied plants possessed a protective effect on testis in different in vivo models as well as antioxidant activities. The effect of these plants on steroidogenesis and the hypothalamic-gonadal axis was also reviewed. The effect of only five plants was studied on sexual behaviour enhancement and three of them were active. Three of the four studied plants enhanced erection. The mechanism of action of active constituents isolated from the studied plants was also investigated. In conclusion, many plants used in Jordanian folk medicine decreased or had no effect on spermatogenesis in animal models. These plants have antioxidant and/or adaptogenic effects, and this may result in a beneficial action on male reproductive system.
... control and Bc^vs. diabetes [61]. It is clearly evident from the literature that GPX5 and Zn are thought to maintain the sperm integrity and prevent early decondensation reaction [60,62,63]. ...
Zinc (Zn) is one of the most important trace elements required for several biological processes. Diabetes negatively affects many organs, and diabetic patients are often hypozincemic. The present study aims to investigate the role of Zn supplementation in the testes, epididymis, and sperms of streptozotocin (STZ)-induced diabetic rat. Serum, testicular, and sperm Zn contents were found to be altered in diabetic rat. Biochemical, histopathological, and protein expression profiles were determined to decipher the role of Zn in protecting the cellular perturbations. Further, histopathological analyses of testes and epididymis showed deranged architecture along with other noted abnormalities. Diabetic testes showed decreased Nrf2, HO-1, SOD1, PCNA, and Bcl-2 expressions whereas increased COX-2, NF-κB, MT, IL-6, and p-ERK levels. SOD1 and GPX5 were decreased in the epididymis of diabetic rat, whereas Zn supplementation attenuated these changes. The present results demonstrate the beneficial role of Zn supplementation in diabetes-associated testicular alterations of rat.
... Zinc deficiency in both a pregnant female and her male fetus or fetuses is likely a contributing cause of the shortening of the penis sheath, the underdevelopment of one or both hemiscrota, and possibly of the misalignment of the hemiscrota [99,100]. Cellular zinc levels have a strong influence on the 5-alpha reductase inhibitor, which converts testosterone into DHT. ...
A significant degradation in the health of wild animals in Montana has been recorded over the past two decades. We surmise that the health issues are related to pesticide exposure. We present some of the evidence of the deterioration of the health in wildlife, which we used to inspire investigations on human health in the US population. While the animals’ exposure is through food, water and air, we believe that human exposure is predominantly through food, as the majority of the population does not reside near agricultural fields and forests. We have obtained US government data on pesticide usage and on human disease patterns over time from the 1998-2010 hospital discharge data. Since glyphosate is by far the most widely used herbicide, we believe it to be a major source of contamination for humans. Correlations between glyphosate usage and specific health issues, along with the known toxicology profile of glyphosate obtained from the literature, reflect a plausible causal relationship. Because much of the wildlife data is from deer fawns, most of the human data presented here involve newborn infants, but we also present some data for children 0-15 years old and for the full population (except newborn). We found many diseases and conditions whose hospital discharge rates match remarkably well with the rate of glyphosate usage on corn, soy, and wheat crops. These include head and face anomalies (R=0.95), newborn eye disorders, newborn blood disorders (R=0.92), newborn skin disorders (R=0.96), lymph disorders in children 0-15 (R=0.86) and in the general population except newborn (R=0.89), congenital heart conditions in newborns (R= 0.98), enlarged right ventricle in all age groups except newborn (R=0.96), newborn lung problems (R=0.95), pulmonary bleeding and edema for all age groups except newborn (R=0.97), liver cancer for all age groups except newborn (R=0.93), newborn metabolic disorders (R=0.95) and newborn genitourinary disorders (R=0.96).
... Zinc supplements are also reputed to decrease aromatization, possibly through reduced circulating luteinizing hormone and testosterone concentrations, alterations in hepatic steroid metabolism, and modification of sex steroid hormone receptor levels and the activity of their zinc fingers, though evidence for this is limited [25]. ...
Testosterone treatment has evolved rapidly over the past 25 years as new, more effective and convenient methods have become available. This study reports experience with seven different methods, introduced on the market in the UK.
To establish the symptom response when testosterone treatment was initiated on the basis of clinical features and symptoms of androgen deficiency, and the resulting endocrine, biochemical and physiological responses.
Of 2693 patients attending the 3 Men's Health Centers - The UK Androgen Study (UKAS), 2247 were treated. Treatments included pellet implants, oral testosterone undecanoate (Testocaps), mesterolone (Proviron), testosterone gel (Testogel), testosterone scrotal cream (Andromen) and scrotal gel (Tostran).
There was no correlation between initial testosterone level, initial symptom score or the success of treatment as defined by adequate resolution of symptoms. Despite the diverse endocrine patterns produced, the testosterone preparations appear equally safe over prolonged periods, with either no change or improvement of cardiovascular risk factors, especially in lowering cholesterol and diastolic blood pressure.
It is suggested that because of excessive reliance on laboratory measures of androgens and undue safety concerns, many men who could benefit from symptom relief, improvement in related clinical conditions and given preventive medical benefits remain untreated.
To verify the nutritional superiority and safety of Protaetia brevitarsis larvae fed a food source containing soybean curd cake, the nutrients and harmful substances of larvae reared only with fermented oak sawdust and a food source containing soybean curd cake were comparatively analyzed. The crude protein content was 50.0% in the larvae fed with a food source containing soybean curd cake (SCC), which was 1.1 times higher than that of the larvae fed with fermented oak sawdust (FOS) at 44.7%. Potassium, which showed the highest content among macrominerals, was 2.5 times higher in SCC (3,169.6 mg/100 g) than in FOS (1,245.9 mg/100 g). Among trace minerals, zinc showed 12.6 times higher content than FOS (8.2 mg/100 g) in SCC (103.0 mg/100 g). As a result of the analysis of harmful substances, all heavy metals met the edible insect control standards, and pathogenic microorganisms , such as E. coli and Salmonella spp, were not detected. According to the above study, the larvae of P. brevitarsis fed soybean curd cake contain various nutrients, and safety has also been confirmed, so it is judged to be suitable for use as food.
Zinc is an essential trace mineral. Dietary zinc deficiency results in stunted growth, skin lesions, hypogonadism, and frequent infections in humans. Mice genetically lacking Slc30a7 suffer from mild zinc deficiency and are prone to development of prostate cancer and insulin resistance. Disease-causing variants or mutations in the human SLC30A7 (ZNT7) gene have not been previously reported. Here we describe two-boy siblings from a French family with stunted growth, testicular hypoplasia, and bone marrow failure. Exome sequencing revealed compound heterozygous variants in ZNT7 consisting of NM_133496.5:c.21dup; p.Asp8ArgfsTer3 and c.842 + 15 T > C inherited from their unaffected mother and father, respectively. The c.21dup variant led to a premature stop codon generated in exon 1 of the ZNT7 coding sequence. RNA-seq analysis demonstrated that the c.842 + 15 T > C variant resulted in a leaky mRNA splicing event generating a premature stop codon right after the splicing donor site of exon 8. Moreover, the expression of ZNT7 protein was remarkably reduced by 80-96% in the affected brothers compared to the control cells. These findings strongly suggest that biallelic variants in SLC30A7 should be considered as a cause of growth retardation, testicular hypoplasia, and syndromic bone marrow failure.
Zinc is a vital trace element for normal function of the living system. In male, zinc is involved in various biological processes, an important function of which is as a balancer of hormones such as testosterone. For this purpose, studies related to the influence of zinc on serum testosterone were selected and summarized, including the effect of dietary zinc deficiency and zinc supplementation on testosterone concentrations. After preliminary searching of papers on databases, 38 papers including 8 clinical and 30 animal studies were included in this review. We concluded that zinc deficiency reduces testosterone levels and zinc supplementation improves testosterone levels. Furthermore, the effect degree of zinc on serum testosterone may vary depending on basal zinc and testosterone levels, zinc dosage form, elementary zinc dose, and duration. In conclusion, serum zinc was positively correlated with total testosterone, and moderate supplementation plays an important role in improving androgen.
Zinc is a chemical element with the symbol Zn and atomic number 30. In the periodic table, Zn belongs in group IIb, along with toxic heavy metals such as Cadmium and Mercury. Yet, zinc is relatively non-toxic for humans and living creatures in general [1].
The Bangkok rooster is a prestigious ornamental bird in Indonesia. Zinc and shell have an aromatase blocker effect that results in testosterone elevations. Additionally, fishbone contains rich protein for optimum biological functions. Serum testosterone regulates comb size in the chicken. This study aimed to investigate the effect of natural aromatase blockers and protein in the comb of Bangkok roosters. This experiment divided thirteen Bangkok roosters into control and treatment groups with zinc, fishbone-shell, and fishbone supplementations. The weekly comb lengthening and widening were intervals between week 0 and the measurement week in this study. The results suggested that fishbone and fishbone-shell supplementations escalated the comb lengthening. Fishbone–shell treatment significantly increased the comb lengthening in the second and fourth weeks (p < 0.05). The significant elongation change in the fishbone group only appeared in the second week (p < 0.05). Otherwise, the treatments produced lower comb widening in the roosters. Fishbone and fishbone-shell supplementation significantly caused a lower widening in every measurement week (p < 0.05). This study uncovered the effects of zinc, shell, and fishbone supplementations on reproductive phenotype in Bangkok roosters.
Trace element deficiency in male lambs is a serious problem. It refers to either insufficient nutrients or mineral elements imbalance. This work aimed to investigate the hormonal and some biochemical changes related to some trace element deficiency and the effect of mineral mixture sup-plementation on these changes. To achieve this aim we induced trace element deficiency in a tested male lambs group (N=10) belonged to our sheep herd and received a mineral mixture as a feed supplement for 10 days. The analysis of tested diet revealed protein 12.32%, calcium 1.21%, phosphorus 0.27%, and zinc 25.96 mg/kg DM. While the control healthy group (N=10) received a traditional diet. The results of serum hormones and biochemical analysis of tested group revealed a significant (P˂0.05) decrease in TSH, T3, T3/T4, tes-tosterone, free testosterone, SHBG, GH, albumin and zinc, with a significant (P˂0.05) increase in T4, total protein and globulin compared to control healthy group. On the other hand, the results obtained after mineral mixture supplementation revealed a significant (P˂0.05) increase of TSH, T3, T3/T4, testosterone, free testosterone, SHBG, GH, albumin and zinc. Also, a significant (P˂0.05) decrease in T4, total protein, and globulin was observed compared with this group before mineral mixture supplementation, with observation of the changes were gradually toward recovery. Moreover, insignificant changes were recorded in calcium, phosphorus and iodine. In conclusion to trace element deficiency have an effect on vital hormones with extension to metabolic process, general health condition and proper growth of male lambs.
Trace element deficiency in male lambs is a serious problem. It refers to either insufficient nutrients or mineral elements imbalance. This work aimed to investigate the hormonal and some biochemical changes related to some trace element deficiency and the effect of mineral mixture supplementation on these changes. To achieve this aim we induced trace element deficiency in a tested male lambs group (N=10) belonged to our sheep herd and received a mineral mixture as a feed supplement for 10 days. The analysis of tested diet revealed protein 12.32%, calcium 1.21%, phosphorus 0.27%, and zinc 25.96 mg/kg DM. While the control healthy group (N=10) received a traditional diet. The results of serum hormones and biochemical analysis of tested group revealed a significant (P˂0.05) decrease in TSH, T3, T3/T4, testosterone, free testosterone, SHBG, GH, albumin and zinc, with a significant (P˂0.05) increase in T4, total protein and globulin compared to control healthy group. On the other hand, the results obtained after mineral mixture supplementation revealed a significant (P˂0.05) increase of TSH, T3, T3/T4, testosterone, free testosterone, SHBG, GH, albumin and zinc. Also, a significant (P˂0.05) decrease in T4, total protein, and globulin was observed compared with this group before mineral mixture supplementation, with observation of the changes were gradually toward recovery. Moreover, insignificant changes were recorded in calcium, phosphorus and iodine. In conclusion to trace element deficiency have an effect on vital hormones with extension to metabolic process, general health condition and proper growth of male lambs.
SUMMARY
The present investigation aimed to study the effects of temperature-humidity index (THI) level, on the
ovarian activity and conception rate of Egyptian Baladi cows. A total number of 40 Baladi cows was used in
this study. The cows were divided into three groups according to time of calving. The first group (15 cows)
calved during (December, January and February) where THI (68.1- 70.5) was considered as (non-heat stress),
the second group calved during (November, March and April) THI (74.5- 76.9) (mild-heat stress=10 cows) and
the third group calved during (May to October) THI (80.1- 83.9) (moderate-heat stress= 15 cows). The results
demonstrated that the percentage of cows that resumed ovarian activity post-partum were significantly
(P<0.05) higher 73.3% in the first group compared to 50 and 33.3% in the second and third groups,
respectively. Incidence, of quiet ovulation was higher (20%) in the second and third groups compared to first
group (18.2%). The percentage of anestrous cases was significantly (P <0.05) higher (50, 66.7%) in the second
and third group compared with the first group (36.4%). Conception rate was significantly (P<0.05) higher
(77.8%) in the first group compared to third group (50%). The intensity of estrus symptoms was significantly
(P<0.05) higher in the first group compared to the second and third groups. In conclusion, the present results
illustrated the detrimental effect of increased temperature-humidity index level (THI) on ovarian activity and
conception rate of Egyptian Baladi cows. This study recommends the stockholders of cows in Aswan
governorate to arrange the cows calvings during the cold months or use some procedures such as sprinkling by
water and fan in order to reduce the hurtful effects of higher THI level on fertility in Egyptian Baladi cows.
Background:
and aims: Benign Prostatic hyperplasia (BPH) is an important public health problem. Roughly half of all men will suffer from BPH related symptoms later in life. The prostate gland, a hormone dependent part of the male reproductive system, is susceptible to internal and external disruptions of regulatory systems. We attempt in this paper to collect available evidence on influence of lifestyle modifications, and naturally occurring substances, plants, micronutrients and supplements on BPH symptoms.
Methods:
Systematic review was performed within the MEDLINE database and Cochrane Library Central Search using a combination of Medical Subject Headings (MeSH) and keywords.
Results:
Moderate exercise and the type and amount of protein intake have a considerable influence on BPH symptoms. The intake of zinc and vitamin D also positively influence BPH symptoms, and so do certain supplements, such as saw palmetto, cemilton and pygeum extracts.
Conclusions:
Lifestyle changes, diet modification and certain nutritional supplements can favorably influence BPH symptoms.
Background: Aromatase is an enzyme converts androstenedione and testosterone to estrone and
estradiol, respectively. According to the role of testosterone and zinc in reducing anxiety and the relation
between androgenic system function and zinc supplementations, in this research, the effect of zinc
chloride injection was analysed in rats which aromatase enzyme was inhibited by aromatase inhibitor
(letrozole).
Materials and Methods: Adult male Wistar rats (weighing 225±25 g) were used. Animals were
divided into 12 groups and based on their weight, aromatase inhibitor (letrozole) was injected
(subcutaneously), and 30 minutes later, ZnCl2 or its solvent (saline) was injected intra-peritoneal. Control
group was received both solvents (DMSO and saline) respectively. Anxiety levels were tested in the
elevated plus maze 30 minutes after the last injection, and thereafter, open field was used for
measurement of the locomotors activity of animals.
Results: The results showed a significant decrease in the percentage of time spent in open arms in
letrozole (1.25 mg/kg) treated group as compared to that of solvent group. The locomotors activity
significantly decreased between letrozole (1.25 mg/kg) with the control group. The combined groups
received letrozole (2.5 mg/kg) and different amounts of zinc chloride (2.5, 5, 10 mg/kg), significantly
reduced (p<0.05) the percentage of time spent in the open arm, comparing to the control group. Groups
that received the combination of zinc chloride (2.5 mg/kg) and different amounts of letrozole (1.25, 5, 10
mg/kg), showed no significant difference in the percentage of entry and time spent in the open arms.
Conclusion: Totally, the present study suggests that letrozole alone increased anxiety and
decreased locomotors activity and could interfere with anxiolytic effect of ZnCl2 as well.
Keywords: Anexiety, Aromatase inhibitor, Letrozole, Rat, Zinc chloride.
La deficiencia de zinc es un grave problema de salud a nivel mundial que afecta a países desarrollados y en vías de desarrollo. A pesar de la evidencia que prueba que la deprivación de zinc en los períodos de rápido crecimiento afecta negativamente el desarrollo cognitivo, cerebral y sexual, se han realizado muy pocos estudios completos en niños. Este trabajo propone una revisión de la evidencia reunida hasta el momento acerca de la relación que existe entre la deficiencia de zinc y el desarrollo intelectual y sexual durante las etapas de la infancia, preadolescencia y adolescencia.
This study aimed to determine whether there were any differences in trace element levels between adolescent boys with gynecomastia and control boys and to determine the correlations between the levels of trace elements and body mass index (BMI) and sex hormones. The pubertal gynecomastia group comprised of 41 patients (mean age = 13.2 ± 0.9 years), who were admitted to Hacettepe University İhsan Doğramacı Children's Hospital in Ankara. Control group comprised of 21 healthy male children. Analyses of trace element levels were performed atomic absorption spectrometry. The mean zinc level of control group was 101.33 ± 16.87 μg/dL and the mean zinc level of gynecomastia group was 81.36 ± 17,43 μg/dL (20% lower in gynecomastia patients, p = 0.0001). However, the mean copper and manganese levels of gynecomastia patients were not statistically different than the control group. There were significant positive correlations between plasma zinc and total testosterone levels in gynecomastia group (r = 0.592; p < 0.05). There was a significant negative correlation between plasma zinc levels and BMI (r = −0.311; p < 0.05). These results indicate that zinc deficiency might be one of the underlying factors of gynecomastia, the importance of which needs to be further elucidated.
Our study investigated the effects of dietary zinc (Zn) deficiency on growth performance, intestinal immune and physical barrier functions of young grass carp (Ctenopharyngodon idella). A total of 630 grass carp (244.14 ± 0.40 g) were fed graded levels of zinc lactate (10.71, 30.21, 49.84, 72.31, 92.56, 110.78 mg Zn/kg diet) and one zinc sulfate group (56.9 mg Zn/kg diet) for 60 days. At the end of the feeding trial, fish were challenged with Aeromonas hydrophila for 14 days. These results indicated that compared with optimal dietary Zn level, dietary Zn deficiency (10.71 mg/kg diet) decreased the production of antibacterial compounds, up-regulated pro-inflammatory cytokines related to nuclear factor kappa B (NF-κB) and down-regulated anti-inflammatory cytokines related to target of rapamycin (TOR) in three intestinal segments of young grass carp (P < 0.05), suggesting that dietary Zn deficiency could impair intestinal immune barrier of fish; decreased the activities and mRNA levels of antioxidant enzymes related to NF-E2-related factor 2 (Nrf2), up-regulated the mRNA levels of caspase-3, -7, -8, -9 related to p38 mitogen activated protein (p38 MAPK) and c-Jun N-terminal protein kinase (JNK), down-regulated the mRNA levels of tight junction complexes (TJs) related to myosin light chain kinase (MLCK) in three intestinal segments of young grass carp (P < 0.05), demonstrating that dietary Zn deficiency could injury intestinal physical barrier of fish. Besides, the Zn requirements (zinc lactate as Zn source) based on percent weight gain (PWG), against enteritis morbidity, acid phosphatase (ACP) activity in the proximal intestine (PI) and malondialdehyde (MDA) content in the PI of young grass carp was estimated to be 61.2, 61.4, 69.2 and 69.5 mg/kg diet, respectively. Finally, based on specific growth rate (SGR), feed efficiency (FE) and against enteritis morbidity of young grass carp, the efficacy of zinc lactate relative to zinc sulfate were 132.59%, 135.27% and 154.04%, respectively.
In this chapter, we discuss the epidemiologic evidence for associations of dietary factors with prostate cancer risk, and the potential for diet to play a role in prostate cancer prevention. We use the conclusions of an authoritative report, Continuous Update Project Report: Diet, Nutrition, Physical Activity, and Prostate Cancer (WCRF International/AICR, 2014), as a starting point, and then review the findings from more recent studies to make an overall assessment of the literature. We include dietary patterns, foods, and dietary constituents that have been associated with an increased or a decreased risk of the disease. Although no specific dietary relationships have been established conclusively, the likelihood that certain dietary components or general eating patterns influence the risk of prostate cancer remains high. Because dietary interventions have the potential to reduce the incidence and improve the survival rates of prostate cancer, continued research on this topic should be a high priority.
This chapter discusses the epidemiologic evidence for associations of dietary factors with prostate cancer risk, and the potential for diet to play a role in prostate cancer prevention. Some findings from animal and in vitro studies, and possible mechanisms for the carcinogenic effects, are presented in support of the epidemiologic findings.. Almost all prostate tumors are classified as adenocarcinomas and occur most commonly in the peripheral zone of the gland. Many cases of prostate cancer are diagnosed as a result of digital rectal examination performed when a man visits his physician for relief of these symptoms. In recent years, the prostate-specific antigen (PSA) test has come into widespread use. This test is not specific for prostate cancer, however, and gives an abnormal result if there is any increased tissue growth in the gland, such as occurs in benign prostatic hyperplasia. Mortality from prostate cancer is low relative to its incidence. This is because prostate cancer is generally well controlled by treatment and occurs at relatively late ages, so that even men who are not cured of the disease often die from other causes. Based on current knowledge, it is not prudent to make very specific dietary recommendations to prevent or treat prostate cancer. However, taken as a whole, the evidence offers reasonably strong support for a diet that emphasizes vegetables, including legumes, and is moderate or lowin the consumption of meat, especially red meat, and dairy products.
Animals require minerals, which act as structural components of organs and tissues, as cofactors or activators in enzyme and hormone systems, as constituents of body fluids and tissues, and as regulators of cell replication and differentiation. Mineral deficiencies, imbalances and toxicity severely inhibit livestock production in the third world countries and are often of more significance compared to the infectious diseases. Deficiencies of certain mineral elements may cause reproductive disorders as minerals play an important role in health and reproduction of the livestock. Infertility and reproductive disorders has emerged as an important problem in our livestock population. Research reported on reproduction and health and clinical records have indicated increasing occurrences of trace mineral deficiencies. Health and production of livestock is thus greatly influenced by optimal level of these mineral elements in the body. If there is imbalance between these minerals either due to deficiency or interaction among themselves, the animal suffers from poor health, immunity and its production is affected. Production is also affected by poor reproductive health resulting from these mineral elements deficiency. Nutrition plays an important role in heifer development, and a variety of nutrients are involved in proper growth and reproductive maturation.
Acridone based highly Zn2+ selective, cell-permeable turn-on fluorescence probe (AAS) shows yellow fluorescence at 560 nm (λex, 445 nm) in dry methanol/DMSO up to 100 µM Zn2+. At Higher Zn2+ concentration (> 100 µM in dry methanol) AAS yields a red solid polymeric complex having strong emission at 605 nm. Interestingly, the red solid polymer also appears at relatively lower Zn2+ concentration (>50 µM) in water. Lowest detection limit of AAS is 0.1 nM of Zn2+. AAS is employed for fluorescence bio-imaging of Zn2+ in human MCF 7 breast cancer cells and HeLa cells. Moreover, AAS develops naked eye orange colour in presence of traces Zn2+ in a mixture of various common cations and anions in solid state (requires no solvent). Hence, the method is ultra green and interference free. AAS can be employed as a laboratory indicator for detection of Zn2+ in real samples and live cells.
The present studies were performed to evaluate the role of zinc in the regulation of testosterone 5 alpha-reduction by the 800 g supernatants prepared from human benign prostate hyperplasia specimens. The results show that when zinc is added at low concentrations the 5 alpha-reduction of testosterone is increased but at higher cation concentrations the metabolism is significantly inhibited. This decrease was mediated by both a non-competitive inhibition of the binding of testosterone to the 5 alpha-reductase enzyme and by a reduction in the formation of the NADPH cofactor. We have also demonstrated that the decreased synthesis of NADPH was produced by a competitive inhibition of both G6P and NADP binding to the G6PD enzyme. The data also suggests that the increase in testosterone metabolism observed at low zinc concentrations does not produce any changes in the binding of testosterone to the 5 alpha-reductase enzyme. In spite of the above observations we were unable to establish any correlation between the endogenous zinc content of the tissue and the in vitro capacity of the BPH samples to 5 alpha-reduce testosterone. The present study suggests a possible physiological role for the regulation of testosterone metabolism by zinc in the human prostate gland.
The direct effect of ethanol on dihydrotestosterone (DHT) conversion to 5α-androstan-3β,17β-diol (3β-diol) and 5α-androstan-3α,17β-diol (3α-diol) by adult rat Leydig cells was examined. Concentrations of ethanol comparable to blood levels of alcoholic men (2.2 – 65 mM) increased DHT conversion to 3β- and 3α-diol, in direct relation to the dose of ethanol added; a 2-fold or greater stimulation was observed. Because this effect was blocked by 4-methylpyrazole or a saturating NADH concentration, these results suggest that this action is mediated by Leydig cell alcohol dehydrogenase activity. These results may have significant impact in the testis and/or other DHT sensitive tissues because ethanol may decrease the availability of the proposed active androgen.
The concentrations of zinc in the prostate are significantly lower in patients with carcinoma of the prostate than in normal control subjects. Although the mechanism responsible for the changes in zinc concentration in the pathological gland remains unexplained, there is now evidence that the metal controls a number of important biochemical functions in the prostate. The purpose of the present article is to review these metabolic functions and to evaluate the significance of zinc measurements in the diagnosis of carcinoma of the prostate.
Cytoplasmic estrogen receptor can exist either free (R) or bound to estradiol-17beta (RE). Both forms can be precipitated from cytosols by protamine sulfate. After protamine precipitation R binds 3-H-estradiol-17beta quantitatively at either 0 degrees or 30 degrees, while precipitated RE binds 3-H-estradiol-17beta only at 30 degrees by exchanging with previously bound hormone. Using these observations, we have developed a method for separate determination of both cytoplasmic R and RE. This method should also be applicable for assay of other steroid receptors, especially in cases where interfering components are present in the whole cytosol.
PIP
A method for separate determination of cytoplasmic free and bound es trogen receptors to estradiol-17beta using protamine precipitation and ligand exchagne is described. Following protamine precipitation the free binds tritiated-estradiol-17beta quantitatively at 0 or 30 degrees while precipitated bound receptor binds only at 30 degrees by exchanging with previously bound hormone. This method may also be useful for assay of other steroid receptors.
The cytosol from livers of adult female mammals contains [3H]estradiol-binding proteins that can translocate to the nucleus
and attach to chromatin. In comparison to the prepubescent rat, adults have higher estrogen binding in the liver and greater
increases in plasma renin substrate after administration of estrogen. The protein in the liver which binds estrogen may be
an estrogen receptor involved in modulating hepatic synthesis of selective plasma proteins.
The role of zinc in gonadal function was investigated in rats. The increases in luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were assayed after intravenous administration of synthetic luteinizing-hormone-releasing hormone (LHRH) to zinc-deficient and restricted-fed control rats. Body weight gain, zinc content of testes, and weight of testes were significantly lower in the zinc-deficient rats compared with the controls. The serum LH and FSH response to LHRH administration were higher in the zinc-deficient rats but serum testosterone response was lower in comparison with the restricted-fed controls. These studies indicate a specific effect of zinc on testes and suggest that gonadal function in zinc-deficient state is affected through some alteration of testicular steroidogenesis.
To examine the metabolism of three 5α-reduced derivatives of testosterone (T) by seminiferous tubules (ST), anterior pituitary (AP) and medial basal hypothalamus (MBH) of adult rats, these tissues were incubated with either tritiated dihydrotestosterone (DHT), α-androstan-3α, 17β diol (3α-adiol) or its 3β-epimer (3β-adiol). The products and residual precursors were quantified using 14C labeled tracers for recovery. Both DHT and 3β-adiol were extensively metabolized. The % DHT metabolized ranged from 60% (MBH) to 93% (ST) with 3α-adiol forming the major product (ST = 69%, AP = 54%, MBH = 38%). The % 3β-adiol metabolized ranged from 68% (ST) to 90% (AP). The metabolism of 3β-adiol by ST differed from that by the other tissues; reversibility of 3β-oxidoreduction, with substantial accumulation of DHT (13%) and 3α-adiol (36%) occurred only with ST. With AP and MBH these metabolites were identifiable only with increased substrate concentrations. In all incubations with AP and MBH with 3β-adiol the bulk of the radioactivity was associated with some polar metabolites (AP = 76%, MBH = 62%). An inverse relationship between polar metabolite formation and 3/gb-oxidation was suggested by the much smaller amounts of such metabolites being formed by ST.In all tissues the bulk of 3α-adiol remained unmetabolized. The % conversion of 3a-adiol to DHT was relatively high for AP and MBH (av = 27%) but low for ST (av = 7%).
The contribution, by peripheral conversion, of androstenedione and testosterone to the circulating estrogens was determined in men with cirrhosis of the liver. The conversion ratio of androstenedione to estrone, estradiol and testosterone and the conversion ratio of testosterone to estrone (but not estradiol) and androstenedione were significantly increased. The plasma concentrations of androstenedione and testosterone were increased and decreased respectively; the mean plasma concentration of androstenedione being similar to that found in normal women. The metabolic clearance rate of androstenedione was not altered in cirrhosis although the metabolic clearance rate of testosterone was decreased. The production rate of androstenedione was elevated while that of testosterone was reduced. The instantaneous contribution of plasma androstenedione to estrone and estradiol was increased in cirrhosis as was the contribution of testosterone to estrone (but not to estradiol). Thus the increased estradiol levels in cirrhosis result, in large part, from increased peripheral conversion from the androgens. The percent contribution of plasma testosterone to plasma androstenedione was decreased although the absolute amount derived by conversion was normal. The percent contribution of plasma androstenedione to plasma testosterone was increased sevenfold in cirrhosis. The fraction of the daily androstenedione production derived from the plasma testosterone pool was not significantly altered. However, a significant fraction of the daily production rate of testosterone was derived from androstenedione. Thus, 15% of the circulating testosterone is not secreted but is derived by peripheral conversion from androstenedione. Normal levels of gonadotropins were found in cirrhosis.
In the past five years there has been a great expansion in our knowledge of the role of zinc in the structure and function of proteins. Not only is zinc required for essential catalytic functions in enzymes (more than 300 are known at present), but also it stabilizes and even induces the folding of protein subdomains. The latter functions have been most dramatically illustrated by the discovery of the essential role of zinc in the folding of the DNA-binding domains of eukaryotic transcription factors, including the zinc finger transcription factors, the large family of hormone receptor proteins, and the zinc cluster transcription factors from yeasts. Similar functions are highly probable for the zinc found in the RNA polymerases and the zinc-containing accessory proteins involved in nucleic acid replication. The rapid increase in the number and nature of the proteins in which zinc functions is not unexpected since zinc is the second most abundant trace metal found in eukaryotic organisms, second only to iron. If one subtracts the amount of iron found in hemoglobin, zinc becomes the most abundant trace metal found in the human body.
Human progesterone receptors (hPRs) are phosphorylated at multiple serine residues, first in a basal step and then in a hormone-induced step. To determine whether hormone-induced phosphorylation precedes or follows the interaction of hPRs with DNA two strategies were used. (i) DNA binding was prevented or altered with site-specific mutants of the A form of hPR; (ii) DNA binding of wild-type hPR forms A and B was prevented with the progesterone antagonist ZK98299. Two hPRA mutants were constructed: DBDCys, which lacks a critical cysteine residue in the first zinc finger, and DBDsp, which is mutated at three discriminatory amino acids to change its DNA binding specificity from a progesterone response element to an estrogen response element. Receptors were transiently expressed in PR-negative cells and were intranuclear. DBDCys did not bind DNA in vitro and DBDsp bound only the estrogen response element. Transiently expressed hPRA and DBDsp showed the upward shift in electrophoretic mobility characteristic of hormone-induced phosphorylation; it was absent with DBDCys. Hormone-induced [32P] orthophosphate incorporation into transiently expressed DBDCys was reduced 60% compared to hPRA and DBDsp but was not eliminated. ZK98299 binds hPRs but prevents their interaction with DNA. Compared to R5020, the antagonist reduced phosphorylation of hPRB and hPRA in T47D breast cancer cells by 60% and totally prevented the mobility shift. We conclude that the hormone-induced phosphorylation of hPR includes DNA-independent and DNA-dependent stages and that only DNA-dependent sites contribute to the mobility shift.
The present study was carried out to investigate if ethanol alters aromatization of androgens and concentrations of hepatic estrogen and androgen receptors. Hepatic aromatization of androgen to estrogen was significantly increased by ethanol administration. There was a significant increase in serum estrogen level but a decreased circulating testosterone level in alcohol-fed rats. Furthermore, the concentration of estrogen receptors in liver cytosol was significantly higher in alcohol-fed rats (37 +/- 5.3 fmol/mg protein), as compared to the intact control value (21 +/- 4.8 fmol/mg protein). However, hepatic androgen receptor levels were much lower (4.4 +/- 0.5) in alcohol-fed rats than those (10.2 +/- 1.4 fmol/mg protein) in control animals. Similarly, castration increased hepatic aromatization of androgens and concentrations of serum estrogen and hepatic estrogen receptors, but it decreased contents of circulating androgen and hepatic androgen receptors. These findings indicate that alcohol administration is considered a chemical form of castration, altering the hepatic steroid metabolism and sex hormone receptor contents and contributing to the pathogenesis of feminization. A combination of alcohol-feeding and castration has no synergistic effect on the hepatic steroid receptors and aromatization, but this combination does have a more profound effect in lowering the concentration of circulating androgen.
The absorption of zinc is increased when the dietary zinc supply is low. This is caused by increased intestinal transport and reduced secretion of endogenous zinc into the intestine. Kinetic analysis of zinc transport, based on data from either the isolated perfused intestine or brush border membrane vesicles, demonstrates uptake velocity is increased homeostatically by a carrier-mediated phase of transport in response to low dietary zinc. Zinc within intestinal cells binds to high molecular weight proteins and metallothionein. Expression of the metallothionein gene is altered by zinc status and the protein appears to have a function in intestinal cells. Zinc transport across the basolateral membrane is also carrier-mediated and may be ATP-driven. Newly absorbed zinc is transported via albumin, first to the liver and then is redistributed to other tissues, particularly muscle and bone which provide the greatest reserves. Plasma zinc levels remain relatively constant except during periods of dietary zinc depletion and acute responses to stress, infection or inflammation where they are depressed. Experiments with intact rats and isolated rat liver parenchymal cells have shown that hepatic zinc turnover is rapid. Stimulation of liver cells by glucocorticoids, glucagon, epinephrine, cAMP or interleukin-1-like factors alters uptake/exchange kinetics such that there is a net accumulation of cellular zinc. Metallothionein gene expression is enhanced by these hormonal signals, and a considerable portion of the newly accumulated zinc is accounted for as that associated with this zinc-binding protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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Androgen binding has been studied in the prostate cytosol of zinc deficient rats by charcoal assays. Rats were housed individually in plastic cages and maintained on a zinc deficient diet for 3 months. The cytosol fraction of prostate gland was incubated with various concentrations of tritiated methyltrienolone (3H-R1881, a synthetic androgen) alone or in the presence of 500-fold excess of radioinert R1881. Scatchard analysis of the data revealed that the number of androgen binding sites in the cytosol fraction of the zinc deficient rat prostate was 31 +/- 5.2 fmol/mg cytosol protein. This was significantly lower than that (84 +/- 11.5 fmol/mg protein) of the controls. Their dissociation constant (Kd = 1.6 +/- 0.6 nM) on the other hand was not different from that (1.7 +/- 0.7 nM) of control animals. This decrease in the concentration of cytosol receptor sites in the zinc deficient state suggests that this metal is involved in the androgen-binding process in the target cells.
This study presents evidence for the direct involvement of zinc in the translation of polypeptide chains in rat liver. Cell-free systems consisting of polyribosomes and fractions, enriched with aminoacyl-tRNA synthetase for incorporation of amino acids into trichloroacetic acid-insoluble proteins, were prepared from livers of three populations of rats: 1) rats fed ad libitum a diet containing 25 ppm zinc; 2) rats fed a diet containing less than 1 ppm zinc; and 3) rats pair fed to the zinc-deficient group a diet containing 25 ppm zinc. Group 2 showed typical signs of zinc deficiency, including decreased bone zinc. The protein synthetic ability of systems isolated from zinc-deficient rats was considerably depressed, resulting in incorporation of 59-69% of the amino acids incorporated by systems from pair-fed rats and 54-59% of those incorporated by ad libitum-fed control animals. This effect was significant after only 14 d of the dietary regimen. Experiments performed by mixing polyribosomes and synthetase fractions from the different groups indicated that a defect is located in the synthetase fraction. Acylation of tRNA by the synthetase fraction also was assayed and found to be 69-90% of that in zinc-sufficient preparations. It is suggested that one or more of the aminoacyl-tRNA synthetase enzymes from the rat liver may be zinc dependent.
Although growth retardation is a common manifestation of zinc deficiency in animals and man, biochemical mechanisms accounting for this phenomenon are not well understood. In our previous studies, ribonucleic acid (RNA)/deoxyribonucleic acid (DNA) was found to be decreased in some of the zinc-deficient tissues of experimental animals. In this study, activities of ribonuclease (RNase) and deoxyribonuclease (DNase) were investigated in the testes, kidneys, bone, and thymus of zinc-deficient, continuously pair-fed and ad libitum-fed control rats. RNase activity was measured by a modified method of Kunitz7,9,10 and DNase activity was determined by a modified method of Sung.11 Nucleuses were measured at both acid and alkaline pH's in all the tissues, except for alkaline RNase and DNase in the bone and alkaline DNase in the thymus, in which case the activities were too low to be measured. Whereas DNase activities showed no difference between the zinc-deficient and pair-fed control rats, the activities of RNase were increased in the zinc-deficient tissues. It is believed that the increased RNase activity may, in part, be responsible for decreased protein synthesis and growth retardation so commonly observed in many animal species, including man.
Homogeneous DNA polymerases from E. coli and sea urchins contain zinc in a proportion of approximately 2 and 4 gm atoms Zn/mole enzyme respectively. Specific inhibition of the enzyme by ortho-phenanthroline and lack of inhibition by meta-phenanthroline suggest that the bound zinc plays a functional role in the interaction of DNA with the polymerases.
Zn2+ potentiates binding of the 4.5S [3H]dihydrotestosterone-receptor complex to isolated rat prostate Dunning tumor nuclei in vitro when assayed in the presence of 300 microM ZnCl2, 3 mM MgCl2, 0.25 M sucrose, 5 mM mercaptoethanol, 0.15 M KCl, and 50 mM tris(hydroxymethyl)aminomethane, pH 7.5. In the presence of 5 mM mercaptoethanol, the concentration of 50 microM total Zn2+ required to promote half-maximal receptor binding to nuclei corresponds to a free Zn2+ concentration of 50 nM. The receptor-nuclear interaction appears to be selective for Zn2+; other divalent cations when added at a concentration of 1 mM to a buffer containing 5 mM mercaptoethanol are less effective (Ni2+) or have essentially no effect (Ca2+, Mg2+, Mn2+, Co2+, Cu2+, and Cd2+). Zn2+ does not alter the sedimentation rate of the 4.5S [3H]dihydrotestosterone receptor in the presence of mercaptoethanol; however, in the absence of mercaptoethanol, Zn2+ causes the receptor to aggregate. Zn2+-dependent nuclear binding of the 4.5S [3H]dihydrotestosterone receptor is saturable at 1.4 X 10(-13) mol of receptor sites/mg of DNA, corresponding to approximately 1150 sites/nucleus. In the presence of excess nuclei, up to 60% of added receptor is nuclear bound. An apparent binding constant for the receptor-nuclear interaction of 10(13) M-1 was approximated. Pyridoxal 5'-phosphate (less than or equal to 10 mM), but not 0.4 M KCl, inhibits Zn2+-dependent nuclear binding of the [3H]dihydrotestosterone receptor. Up to 66% of nuclear-bound receptor can be extracted in buffer containing 3 mM ethylenediaminetetraacetic acid plus either 0.4 M KCl or 10 mM pyridoxal 5'-phosphate.(ABSTRACT TRUNCATED AT 250 WORDS)
During the past two decades, the essentiality of zinc for man has been established. Deficiency of zinc in man due to nutritional factors and several diseased states has been recognized. High phytate content of cereal proteins decreases availability of zinc; thus the prevalence of zinc deficiency is likely to be high in a population subsisting mainly on cereal proteins. Alcoholism is known to cause hyperzincuria and thus may play a role in producing zinc deficiency in man. Malabsorption, cirrhosis of the liver, chronic renal disease and other chronically debilitating diseases may similarly induce zinc deficiency in human subjects. A severe deficiency of zinc has recently been recognized to occur in patients with sickle cell anemia and a beneficial effect of zinc therapy in such patients has been reported. Growth retardation, male hypogonadism, skin changes, poor appetite, mental lethargy and delayed wound healing are some of the manifestations of chronically zinc-deficient human subjects. Taste abnormalities, correctable with zinc supplementation, have been observed in uremic subjects. Recently, abnormal dark adaptation related to zinc deficiency in patients with cirrhosis of the liver and sickle cell disease has been reported. In severely zinc-deficient patients, dermatological manifestations, diarrhea, alopecia, mental disturbances and intercurrent infections predominate and if untreated the condition becomes fatal. Zinc deficiency is known to affect testicular functions adversely in man and animals. This effect of zinc is at the end organ level and it appears that zinc is essential for spermatogenesis and testosterone steroidogenesis. Zinc is involved in many biochemical functions. Several zinc metalloenzymes have been recognized in the past decade. Zinc is required for each step of cell cycle in microorganisms and is essential for DNA synthesis. Thymidine kinase, RNA polymerase, DNA-polymerase from various sources and RNA-dependent DNA polymerase from viruses have been shown to be zinc-dependent enzymes. Zinc also regulates the activity of RNase; thus the catabolism of RNA appears to be zinc-dependent. The effect of zinc on protein synthesis may be attributable to its vital role in nucleic acid metabolism. The activities of many zinc-dependent enzymes have been shown to be affected adversely in zinc-deficient tissues. Three enzymes, alkaline phosphatase, carboxypeptidase and thymidine kinase, appear to be most sensitive to zinc restriction in that their activities are affected adversely within three to six days of institution of a zinc-deficient diet to experimental animals.(ABSTRACT TRUNCATED AT 400 WORDS)
The effects of zinc deficiency on protein synthesis and expression of specific mRNAs were assessed in rat liver. Zinc deficiency had no apparent effect on liver weight, protein content, or RNA content when these properties were compared with values obtained using pair-fed rats. However, zinc deficiency resulted in a lower rate of hepatic protein synthesis. The decreased rate of protein synthesis was due to a decrease in the rate of synthesis of proteins retained in the liver, with no apparent change in the synthesis of secreted proteins. Analysis of expression of specific gene products, as assessed by in vitro translation of total RNA followed by two-dimensional gel analysis, showed that the expression of only a few mRNAs was altered by zinc deficiency. The patterns of change in gene expression resulting from zinc deficiency varied from almost complete repression to full expression. In additional studies, cDNA clones to serum retinol-binding protein and transthyretin were used to examine the effect of zinc deficiency on the relative abundance of mRNA for these two proteins. The relative abundance of mRNA for transthyretin was specifically elevated as a result of zinc deficiency. In contrast, the relative abundance of mRNA for hepatic serum retinol-binding protein was increased in both zinc-deficient and pair-fed rats. Therefore, the observed change in mRNA for serum retinol-binding protein was apparently at least in part due to the inanition that accompanies zinc deficiency. Overall, the results suggest that zinc can regulate the synthesis of specific proteins in rat liver through changes in the relative abundance of specific mRNAs.
Of the nine biological trace elements, zinc, copper and selenium are important in reproduction in males and females. Zinc content is high in the adult testis, and the prostate has a higher concentration of zinc than any other organ of the body. Zinc deficiency first impairs angiotensin converting enzyme (ACE) activity, and this in turn leads to depletion of testosterone and inhibition of spermatogenesis. Defects in spermatozoa are frequently observed in the zinc-deficient rat. Zinc is thought to help to extend the functional life span of the ejaculated spermatozoa. Zinc deficiency in the female can lead to such problems as impaired synthesis/secretion of (FSH) and (LH), abnormal ovarian development, disruption of the estrous cycle, frequent abortion, a prolonged gestation period, teratogenicity, stillbirths, difficulty in parturition, pre-eclampsia, toxemia and low birth weights of infants. The level of testosterone in the male has been suggested to play a role in the severity of copper deficiency. Copper-deficient female rats are protected against mortality due to copper deficiency, and the protection has been suggested to be provided by estrogens, since estrogens alter the subcellular distribution of copper in the liver and increase plasma copper levels by inducing ceruloplasmin synthesis. The selenium content of male gonads increases during pubertal maturation. Selenium is localized in the mitochondrial capsule protein (MCP) of the midpiece. Maximal incorporation in MCP occurs at steps 7 and 12 of spermatogenesis and uptake decreases by step 15. Selenium deficiency in females results in infertility, abortions and retention of the placenta. The newborns from a selenium-deficient mother suffer from muscular weakness, but the concentration of selenium during pregnancy does not have any effect on the weight of the baby or length of pregnancy. The selenium requirements of a pregnant and lactating mother are increased as a result of selenium transport to the fetus via the placenta and to the infant via breast milk.
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