R Voutilainen's research while affiliated with Kuopio University Hospital and other places
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Publications (80)
Study question:
Does treatment of constitutional delay of growth and puberty (CDGP) in boys with aromatase inhibitor letrozole (Lz) or conventional low-dose testosterone (T) have differing effects on developing seminiferous epithelium?
Summary answer:
Anti-Müllerian hormone (AMH) declined similarly in both treatment groups, and the two Sertoli c...
Altered glucocorticoid activity is one possible mechanism linking fetal growth restriction with later insulin resistance (IR) and type 2 diabetes. We aimed to investigate whether serum glucocorticoid parameters are related to IR in children born small for gestational age (SGA).
A total of 110 children (55 age- and gender-matched pairs born SGA or a...
Diabetic retinopathy (DR) represents a common complication of type 2 diabetes mellitus. Appearance of DR lesions such as microaneurysms, haemorrhages, hard and soft exudates, IRMA and neovascularisation reflect the severity of DR. The aim of our study was to investigate the association of selected glycaemic parameters with particular DR abnormaliti...
The members of the Wnt glycoprotein family are important in embryogenesis and adult tissue homeostasis, and deletion of WNT-4 gene in mice leads to improper development of many organs including the adrenals. The objective of this study was to investigate the expression of WNT-4 gene in human adrenals and adrenocortical tumors. The WNT-4 mRNA expres...
For a particularly long time, automatic diagnosis of diabetic retinopathy from digital fundus images has been an active research topic in the medical image processing community. The research interest is justified by the excellent potential for new products in the medical industry and significant reductions in health care costs. However, the maturit...
Aberrant DNA methylation may be involved in human adrenocortical tumorigenesis, which is often accompanied by abnormal hormone production. In this study, we aimed to clarify the effects of DNA methylation on steroidogenesis using the human adrenocortical NCI-H295R cell line as a model. Treatment with the DNA methylation inhibitor 5-aza-2'-deoxycyti...
Germline mutations in the succinate dehydrogenase (SDH) (mitochondrial respiratory chain complex II) subunit B gene, SDHB, cause susceptibility to head and neck paraganglioma and phaeochromocytoma. Previously, we did not identify somatic SDHB mutations in sporadic phaeochromocytoma, but SDHB maps to 1p36, a region of frequent loss of heterozygosity...
Transcription factors GATA-4 and GATA-6 are expressed during normal adrenocortical development in mice and humans, and in vitro studies have linked them to adrenal steroidogenesis. GATA-4 is highly expressed in the adrenocortical tumors of gonadectomized mice, whereas GATA-6 is down-regulated in the tumor area. Based on these findings we studied GA...
Adrenocorticotropin is the major regulator of adrenocortical development and function. It acts mainly through the cAMP-dependent protein kinase A (PKA) pathway. Our aim was to study the interaction of tumor necrosis factor-alpha (TNFalpha) and the PKA pathway in adrenocortical cell proliferation and apoptosis. The PKA activator Dibutyryl cAMP ((Bu)...
Transcription factors GATA‐4 and GATA‐6 are expressed during normal adrenocortical development in mice and humans, and in vitro studies have linked them to adrenal steroidogenesis. GATA‐4 is highly expressed in the adrenocortical tumors of gonadectomized mice, whereas GATA‐6 is down‐regulated in the tumor area. Based on these findings we studied GA...
Activins and inhibins are structurally related glycoprotein hormones modulating pituitary FSH secretion and gonadal steroidogenesis. Activins and inhibins are also produced in the adrenal cortex where their physiological role is poorly known. Hormonally active human adrenocortical tumors express and secrete inhibins, while in mice adrenal inhibins...
Our earlier work implicates transcription factors GATA-4 and GATA-6 in the murine adrenal. We have now studied their expression during mouse and human adrenal development in detail. GATA-4 and GATA-6 mRNAs are readily detectable from embryonic day 15 in mouse and gestational week 19 in human adrenal cortex. In postnatal adrenal, GATA-4 expression i...
Activin and its binding protein follistatin may act as local regulators of cell growth and steroidogenesis in the human ovary. The recently identified follistatin-related gene (FLRG) is expressed abundantly in the human ovary, has high affinity for activin, and is able to inhibit activin-induced transcriptional responses. However, little is known a...
Mutations in genes encoding the two subunits of the beta-cell ATP-sensitive potassium channel (K(ATP)) channel (SUR1 and Kir6.2) are the major cause of congenital hyperinsulinism (CHI). In this study, the K(ATP) channel genes were screened in a population-based study that included all verified Finnish CHI patients (n = 43) in a 27-yr period. Seven...
Pituitary gonadotropins mediate part of their effects on ovarian function via local hormones and growth factors produced by granulosa cells. Activins and inhibins are among these factors, and they have often opposite effects on various components of the reproductive system. The purpose of this study was to investigate the regulation of ovarian acti...
Longitudinal studies on bone mineral density (BMD) accrual in young children are scarce. The purpose of the present study was to evaluate prospectively the development of spinal BMD in healthy Finnish children aged 3–6 y by dual-energy x-ray absorptiometry (DXA). Lumbar spine (L2-L4) areal BMD (g/cm2) was measured by DXA (Lunar DPX) in 20 children...
Our earlier work implicates transcription factors GATA-4 and GATA-6 in the murine adrenal. We have now studied their expression during mouse and human adrenal development in detail. GATA-4 and GATA-6 mRNAs are readily detectable from embryonic day 15 in mouse and gestational week 19 in human adrenal cortex. In postnatal adrenal, GATA-4 expression i...
During the human menstrual cycle, serum inhibin concentrations fluctuate in a cyclic fashion. To examine the regulation of inhibin/activin beta(B) subunit gene expression in ovarian granulosa-luteal cells, the levels of beta(B) subunit mRNA were determined in primary cultures of human granulosa-luteal cells treated with gonadotrophins and protein k...
Automatic circuitry for monitoring an RF SQUID sensor is described. The system performs several trimming procedures and provides an output in terms of the flux quantum. Circuit diagrams and adjustment procedures are discussed.
Angiogenesis is an important component in many biological processes and also in pathologic conditions including neoplastic diseases. Vascular endothelial growth factor (VEGF) is a secreted endothelial cell-specific growth factor, which is induced by tissue hypoxia and is angiogenic in vivo. Adrenal gland is a well-vascularized organ, and the roles...
Inhibins are gonadal glycoproteins with endocrine effects on pituitary FSH secretion and para/autocrine effects on ovarian and testicular function. The purpose of this study was to investigate the endocrine and para/autocrine regulation of inhibin A and inhibin B secretion in human ovarian granulosa-luteal cells. The cells were obtained from women...
Corticosteroids are synthesized from cholesterol which may arise from de novo synthesis or from the uptake of low or high density lipoproteins (LDL or HDL). In the present study, we compared the expression and regulation patterns of LDL receptor and CLA-1 (CD36 and LIMPII Analogous-1, an HDL receptor) genes in adult human adrenocortical tissues to...
Inhibins are gonadal glycoprotein hormones whose main endocrine function is to inhibit pituitary FSH secretion. In addition to testes and ovaries, other steroid-producing organs are sites of inhibin alpha subunit expression. To study the role of inhibins in human adrenal gland, we screened a panel of 150 adrenals (10 normal adrenals, 25 adrenocorti...
Activin A (a homodimer of two activin betaA subunits) has been shown to induce the neuronal differentiation of rat pheochromocytoma PC12 cells. We studied activin A and its receptor gene expression in human pheochromocytomas in vivo and in vitro to clarify the potential involvement of activin A in the pathophysiology of these tumors. We first scree...
A nationwide search of patients with classical 21-hydroxylase deficiency (21-OHD) was performed in Finland to determine the long-term outcome of the disease. In total, 108 patients were found. Fifty-four patients (50%, 31F, 23M) had deficiency of a salt-wasting form and another 54 (50%, 29F, 25M) had a simple virilizing form of 21-OHD. A significan...
Though appropriate glucocorticoid substitution therapy should abolish both cortisol deficiency and adrenal androgen excess in patients with 21-hydroxylase deficiency (21-OHD), the long-term outcome is not always satisfactory. There are several reports on low adult height in both male and female patients, and impaired fertility has been reported in...
Bone morphogenetic protein (BMP-6, also known as vegetal-pale-gene-related and decaplentaplegic-vegetal-related) is a member of the transforming growth factor-beta superfamily of multifunctional signaling molecules. BMP-6 appears to play various biological roles in developing tissues, including regulation of epithelial differentiation. To study the...
The expression of the neuropeptide Y (NPY) gene varies considerably in human pheochromocytomas, but the mechanisms for this variation have not been clarified. To investigate the regulation pattern of the NPY gene in human pheochromocytomas, we screened 16 pheochromocytomas and 9 normal adrenal tissues with Northern blots. The expression level of NP...
The cDNA clone pG2 was originally isolated from a human pheochromocytoma. The respective gene was found to be strongly expressed in normal adrenal zona glomerulosa and medulla, as well as in Conn's adenomas and pheochromocytomas. To shed more light on the expression and regulation of the pG2 gene, we investigated its expression in a wide variety of...
The insulin-like growth factor (IGF) system appears to be important in the regulation of adrenal growth and hormone synthesis. As IGF-binding proteins (IGFBPs) modify IGF bioactivity, we investigated the expression of IGFBP 1-6 genes in different adrenal tumors and hyperplasias to further clarify the role of the IGF system in adrenal pathophysiolog...
We studied the expression of inhibin alpha-subunit in normal and hyperplastic adrenal glands, as well as in various adrenocortical tumors. The protein expression of inhibin alpha was performed by immunohistochemistry. Virilizing adenomas showed strong immunoreactivity against monoclonal inhibin alpha-subunit antibody, whereas other adenomas were on...
Insulin-like growth factors I and/or II are expressed in adrenal cells, and modulate their proliferation and steroid hormone synthesis suggesting that they may function as paracrine/autocrine factors. In some species, at least ACTH induces insulin-like growth factor synthesis. Thus, these peptide growth factors mediate at least some of the effects...
We studied the expression of inhibin α-subunit in normal and hyperplastic adrenal glands, as well as in various adrenocortical tumors. The protein expression of inhibin α was performed by immunohistochemistry. Virilizing adenomas showed strong immunoreactivity against monoclonal inhibin α-subunit antibody, whereas other adenomas were only weakly po...
Adrenomedullin (ADM) is a polypeptide originally discovered in a human pheochromocytoma and is also present in normal adrenal medulla. It has been proposed that ADM could be involved in the regulation of adrenal steroidogenesis via paracrine mechanisms. Our aim was to find out if ADM gene is expressed in adrenocortical tumors and how ADM gene expre...
We analysed a well-characterized group of 83 patients (43 men, 40 women; mean age +/- SEM: 65.5 +/- 0.6 years at the 10-year examination) with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and in 123 control subjects (56 men, 67 women; mean age +/- 0.9 years) retrospectively for the relationship of apolipoprotein E (apo E) genotypes (E2/...
Abundant c-myc gene expression in neoplasms has been often linked to poor prognosis. As c-myc mRNA is expressed and hormonally regulated in human adrenals, we examined the c-myc gene expression in adrenal tumors by RNA analysis and immunohistochemistry to find out the possible role of c-myc in adrenal neoplasms. The abundant expression of the c-myc...
H19 is an imprinted maternally expressed gene, which is not translated to protein and functions as an RNA molecule. It is closely related to the oppositely imprinted paternally expressed insulin-like growth factor 2 (IGF-2). While the biological function of H19 is not understood IGF-2 is a growth factor that plays a role in human follicular and end...
Our aim was to assess adrenocortical function in very low birth weight infants, specifically to evaluate the impact of gestational age and dexamethasone (DEX) therapy on serum concentrations of total and free cortisol, dehydroepiandrosterone sulfate (DHEAS), and steroid-binding globulins. Twelve moderately preterm or full-term neonates of 38 +/- 4...
Determinations of serum gonadotropin concentrations by ultra-sensitive methods have improved the diagnosis of pubertal disorders. The onset of puberty can be estimated by measuring serum gonadotropin pulsation, but as this requires serial nocturnal blood sampling, it is not a routine investigation. Gonadotropin measurements in first morning voided...
Determinations of serum gonadotropin concentrations by ultra-sensitive methods have improved the diagnosis of pubertal disorders. The onset of puberty can be estimated by measuring serum gonadotropin pulsation, but as this requires serial nocturnal blood sampling, it is not a routine investigation. Gonadotropin measurements in first morning voided...
The steroidogenic acute regulatory protein (StAR) has recently been shown to be a factor necessary for cholesterol transport into adrenal and gonadal mitochondria, which is the regulated, rate-limiting step in steroidogenesis. We show here that StAR mRNA is highly expressed in normal adult adrenals ( n =9), adrenocortical adenomas ( n =16), adrenal...
We have analyzed the expression of the c -myc proto-oncogene in human adrenal glands in vivo and in primary cell cultures by Northern blot analysis. c- myc mRNA was consistently expressed in all human adrenals studied. Expression in adult adrenals was found to be approximately 50% of that in fetal adrenals, but much higher than that in adult liver...
Expression of the messenger ribonucleic acids (mRNAs) for insulin-like growth factors (IGFs), their binding proteins (IGFBP1 through IGFBP-6), and receptors was examined in normal and polycystic human ovaries (PCO). Northern and dot blots and RT-PCR were used to evaluate mRNA levels. The IGF system was studied in fresh granulosa, stromal, and theca...
We recently described an infantile onset spinocerebellar ataxia (IOSCA) in 19 Finnish patients. The classification of hereditary ataxias of unknown etiology is difficult because of the heterogeneity of these diseases. The clinical course of IOSCA is homogeneous. Ataxia, muscle hypotonia, athetosis, and loss of deep tendon reflexes in the legs appea...
Unlabelled:
In a follow up study of 34 patients with premature adrenarche we examined serum adrenal androgen levels and growth. The majority (28/34) showed an upward bend in the growth curve which, at the mean age of 2.3 years, preceded other signs of adrenarche on average by 3.8 years. Pubertal growth spurt was missing or reduced in 50% of the pa...
Serum levels of LH and FSH are very low from about 2 yr of age to the onset of puberty, which is heralded by a very sharp increase in LH levels. We studied age-related changes in urinary gonadotropins in a total of 184 boys and girls of various ages. Urinary FSH and LH were measured by ultrasensitive time-resolved immunofluorometric assays. The det...
Serum levels of LH and FSH are very low from about 2 yr of age to the onset of puberty, which is heralded by a very sharp increase in LH levels. We studied age-related changes in urinary gonadotropins in a total of 184 boys and girls of various ages. Urinary FSH and LH were measured by ultrasensitive time-resolved immunofluorometric assays. The det...
The expression of H19 and insulin-like growth factor-II (IGF-II) genes is important for fetal growth, and the misexpression of these genes may also be involved in the development of some tumors. In human fetal adrenals, H19 and IGF-II expression levels are very high. We show here that H19 is strongly expressed (approximately 50% of the expression i...
Glucocorticoids are known to inhibit growth in many different cell types. Although corticosterone is secreted by the adrenal cortex, its direct effect on the growth of different zones is poorly determined. We studied the effects of corticosterone on cell proliferation and cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc; the rate-lim...
Human phaeochromocytomas abundantly express insulin-like growth factor-II (IGF-II), but its regulation and biological role in these neoplasms is not known at present. To clarify the regulation of IGF-II gene expression in phaeochromocytomas, we studied the effects of glucocorticoids, nerve growth factor (NGF), and protein kinase A and C regulators...
In a girl aged 5 years with a virilizing adrenal adenoma the urinary and plasma steroid findings suggested the diagnosis of congenital adrenal hyperplasia due to P450c11 (11 beta-hydroxylase) deficiency. After removal of the tumour clinical signs receded and the hormonal values normalized. RNA analysis of the tumour tissue revealed low amounts of P...
ACTH exerts a biphasic effect on the growth of fetal rat adrenocortical cells in primary culture when bromodeoxyuridine (BrdU) incorporation is used as an indicator of proliferation. The immediate inhibitory effect during the first 24 h of ACTH stimulation is not dependent on cyclic AMP (cAMP). Protein kinase C (PKC) inhibitors H-7 and staurosporin...
Adjacent, parentally imprinted, insulin-like growth factor-II (IGF-II) and H19 genes are highly expressed during embryogenesis and are important for fetal growth. Human fetal adrenals express abundantly both IGF-II and H19 genes. To clarify the significance and regulation of the H19 gene, we studied its expression in fetal adrenals. In situ hybridi...
ACTH has a biphasic effect on the proliferation of fetal rat adrenocortical cells in primary culture. Dramatic changes occurred during the first 72 h of ACTH stimulation, when incorporation of bromodeoxyuridine was used as an indicator of proliferation. The primary effect of ACTH was the inhibition of proliferation during the first 24 h, which was...
Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) regulate cell proliferation and functional maturation through the EGF receptor (EGF-R). Their roles in human tooth development and odontogenic tumorigenesis have not been explored. We studied the expression of EGF, TGF-alpha and EGF-R in human fetal teeth (cap stage to e...
An increasing body of evidence suggests that insulin-like growth factors (IGFs) are important in the development of some tumors. In the present study, we investigated the gene expression of IGF-I, IGF-II, and their receptors in different adrenal tumors and hyperplasias. Four adrenocortical carcinomas, 15 adenomas, 4 pheochromocytomas, 5 nodular hyp...
To understand the development of the human pancreas better, we studied the expression and regulation of insulin, insulin-like growth factor-II (IGF-II) and transforming growth factor-α (TGF-α) genes in the human fetal pancreas and islet-like cell clusters (ICC) from the second trimester human fetuses. Northern blot analysis revealed an abundant exp...
Insulin-like growth factor-II (IGF-II) may be one of the most important local growth factors in human fetal adrenals (HFAs), where its mRNA levels are upregulated by ACTH. We have investigated whether protein kinase C (PKC)-dependent mechanisms and various polypeptide growth factors participate in the regulation of IGF-II gene expression in culture...
Urinary protein excretion rate and clinical and metabolic associates were investigated in a group of 108 patients with Type 2 diabetes mellitus at the time of diagnosis and after 5 years, and also 121 control subjects. The presence of coronary heart disease, neuropathy and retinopathy, cardiovascular risk factors and 24-h urinary excretion rate of...
In order to avoid invasive sampling in pediatric patients, we examined the concentrations of LH and FSH in paired serum and urine samples from 43 children (age 0-16 yr) who had no interfering disorders or medication. Highly sensitive time-resolved immunofluorometric assay (IFMA) kits were obtained from Pharmacia-Wallac, Turku, Finland (LH and FSH D...
Inhibin subunit messenger ribonucleic acids (mRNAs) are expressed during the gonadal development of rodent, ovine, and bovine fetuses. We investigated the expression of inhibin subunit mRNAs in human fetal gonads between 13 and 25 weeks of gestational age. In testes, the alpha-subunit mRNA was highly expressed at the beginning of the second trimest...
Gonadal differentiation may be divided into four stages: pregonadal, indifferent, primary sex differentiation, and secondary sex differentiation. Sertoli cells appear at 6-7 weeks and Leydig cells differentiate at 8 weeks, but in ovaries, primary sex differentiation occurs much later. Testosterone secretion peaks at 12-16 weeks causing male seconda...
In human placenta the enzyme complex aromatase catalyzes the conversion of androgens to estrogens and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) mediates the reversible interconversion of, e.g. estrone to estradiol. We studied the effects of cholera toxin (CT), an activator of adenylate cyclase, and 12-O-tetradecanoyl phorbol 13-acetate (TP...
In human placenta the enzyme complex aromatase catalyzes the conversion of androgens to estrogens and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) mediates the reversible interconversion of, e.g. estrone to estradiol. We studied the effects of cholera toxin (CT), an activator of adenylate cyclase, and 12-O-tetradecanoyl phorbol 13-acetate (TP...
The cholesterol side-chain cleavage enzyme (P450scc) is the rate-limiting and hormonally regulated step in steroid hormone synthesis. Cyclic AMP (cAMP) is thought to be the main second messenger regulating steroid hormone synthesis in all steroid producing organs. We studied the effects of 12-0-tetradecanoyl phorbol 13-acetate (TPA), an activator o...
Pre- and post-operative growth was analysed in eight children with Cushing syndrome. Six children had Cushing's disease; three of them were treated by bilateral adrenalectomy and three by transphenoidal pituitary adenectomy. One child had an adrenocortical adenoma and another primary adrenocortical nodular dysplasia. The typical cushingoid habitus...
Adrenocortical steroid secretion was studied in 10 infants (mean age 8.9 months, range 5-22 months) during and after ACTH therapy for infantile spasms. Long-acting ACTH (Acortan prolongR., Ferring, Sweden) was given i.m. once daily, 80 units during the first 3 weeks, 40 units during the following 2 weeks with tapering and termination within the nex...
18 girls with premature adrenarche were evaluated both clinically and by serum steroid measurements. Age at first appearance of the symptoms ranged from 3.0 to 7.8 years. Clinical findings included pubic or axillary hair, acne, accelerated growth, adult-type perspiration and oily skin or hair. Bone age was 0.3-3.2 years ahead of chronological age....
The secretion of hCG, progesterone, estradiol, estrone, DHA (dehydroepiandrosterone) and androstenedione was studied in tissue culture of human midterm placenta. Radioimmunoassay and gas-liquid chromatography were used in hormone measurements. Considerable amounts of progesterone and hCG were secreted during the 18-day cultivation period. The secre...
The present study investigates the regulation of human fetal adrenal steroidogenesis. Adrenals were cultured alone or together with placental tissue. The main secretory products of adrenals were analysed by gas liquid chromatography from tissue culture medium. ACTH stimulated both the cortisol and dehydroepiandrosterone sulphate (DHAS) production o...
Early events during ACTH-induced differentiation of cortical cells of human fetal adrenals in primary cultures were studied by electron microscopy and steroid analysis. In undifferentiated cortical cells, the basal secretion of steroids was very low. The first sign of ACTH stimulation was a marked increase in pregnenolone sulfate secretion during t...
The effects of corticosterone and cortisol in concentrations attainable in the adrenal gland were studied on ACTH-induced steroidogenesis in cultured cortical cells of foetal human and rat adrenals. Corticosterone at a concentration of 5.8 × 10 ⁻⁵ mol/l clearly inhibited cortisol production (65.5%; P < 0.005) and simultaneously increased androgen p...
Endogenous steroid secretion and the conversion of exogenous pregnenolone and progesterone were studied in tissue culture of human mid-term fetal adrenals. Addition of pregnenolone on the first day of cultivation caused an increase in DHAS (dehydroepiandrosterone sulphate) and pregnenolone sulphate secretion during the first cultivation days, but n...
Citations
... In addition, these techniques also require specialized technicians, complex sample pretreatment, and highly time-consuming, which limits the expansion of their application scope. As alternatives to the above methods, immunoassays including radioimmunoassay (RIA) [19], enzyme linked immunosorbent assay (ELISA) [20], chemiluminescence [21], and electrochemiluminescence analysis [22] are developed for analyzing testosterone. Although these methods exhibit unique advantages of safety, low cost, and environment-friendly [18]. ...
... However, clinical symptoms may still occur as a result of an increased tumor mass and overall high levels of steroid precursors, which affect target tissues either directly or after peripheral transformation to more biologically active derivatives, which is observed in case of androgen. Importantly, the presence of increased amounts of steroid precursors in the blood, along with clinical symptoms, may be mistakenly interpreted as a biochemical sign of CAH (Werder et al. 1994). It has been shown in vitro that tumor tissue can be characterized by low activity of many enzymes with a simultaneous, selective increase in the activity of one or several enzymes with high affinity to unusual substrates. ...
... The placental I.1 aromatase promoter is localized 93 kb upstream of the coding region exon II-X of the CYP19 gene and its activation produces CYP19 transcript with exon I.1 spliced onto a common splice junction directly upstream from exon II [10]. The regulation of placental estrogens synthesis by aromatase in the trophoblast is known to be increased by factors including calcitriol [11], hGCMa, a mammalian homolog of the protein encoded by the Drosophila glial cells missing (gcm) gene [12], normoxic reduction of inhibitory factor Mash-2 [13], and the AP-2 family of transcription factors (through the second messenger cAMP) [12], as well as activators of the protein kinase C (PKC) signaling pathway [14,15]. The precise role of the PKC signaling pathway in the regulation of CYP19 gene expression remains to be clarified. ...
Reference: Klempan-2011
... Due to the unavailability of a different assay for detecting intact U-LH-ir in this study, the non-intact LH-ir could not be determined as the arithmetic difference between total and intact LH-ir as performed in our previous studies (11,12). Therefore, inference to the non-intact U-LH-ir levels was made by calculating the proportion of total U-LH-ir to intact S-LH-ir ( Figure 2) because of the high correlation between U-LH-ir and S-LH-ir at similar absolute concentrations as shown in our earlier studies (14)(15)(16). The assays were performed according to the instructions of the manufacturer. ...
... Due to the unavailability of a different assay for detecting intact U-LH-ir in this study, the non-intact LH-ir could not be determined as the arithmetic difference between total and intact LH-ir as performed in our previous studies (11,12). Therefore, inference to the non-intact U-LH-ir levels was made by calculating the proportion of total U-LH-ir to intact S-LH-ir ( Figure 2) because of the high correlation between U-LH-ir and S-LH-ir at similar absolute concentrations as shown in our earlier studies (14)(15)(16). The assays were performed according to the instructions of the manufacturer. ...
... If GATA4 and WT1 are considered two of the main regulators for the initial formation of the AGP, their expression in mice is switched off in the AP, just after its separation from the GP occurs [13,128]. This suggests that these genes prevent the differentiation of AGP cells into the adrenal steroidogenic cell lineage. ...
... GATA1-3 are primarily involved in haematological development, whereas GATA4 and GATA6 have been implicated in human CYP17A1 expression. GATA6 is highly expressed in the adrenal cortex and the stimulatory actions of GATA6 on CYP17A1 transcription are independent of DNA binding but occur through the interaction of GATA6 with specificity protein 1 (Sp1) (Kiiveri et al. 2004;Sewer and Jagarlapudi 2009). ...
... Inhibins counteract the biological effects of activin by antagonizing activin type II receptor and formation of an inactive complex with the TGFβ type III receptor β-glycan. Adrenocortical cells are able to express both α and β subunits (54)(55)(56). In particular, the α-inhibin is expressed in the zona reticularis under the positive control of ACTH, whereas β-subunits are mainly present in the outer cortex. ...
... Table 2 illustrates an overview of all open-source datasets of DR [30]. [19] 88,702 (433×289) to (5,185×3,456) DDR [20] 13,673 Varies ODIR [31] 10,000 -APTOS 2019 [25] 3,660 Varies RFMiD [24] 3,200 (2,144×1,424) Messidor [23] 1,200 (1,440×960) to (2,304×1,536) 24-bit Messidor-2 [23] 1,784 (1,440×960) to (2,304×1,536) 24-bit IDRiD [32] 516 (4,288×2,848) DIARETDB0 [21] 130 (1,500×1,152) 24-bit DRIVE [29] 40 (565×584) 24-bit DIARETDB1 [33] 89 (1,500×152) 24-bit ...
... Blood and urine samples were collected from type2 diabetic patients in the morning between 08:00 and 10:00 O'clock to minimize the effect of diurnal variation (10) , after a period of fasting 8-10 hours by vein puncture using 5 ml disposable syringes and it was divided into two parts: one part about 2 ml was put in EDTA containing tube; the blood was mixed gently for 3 minutes and then used for hematological tests and especially for HbA1c assay. The second part included 3 ml of blood was put in the centrifuge tube (glass tube) and allowed to clot for 15 min then it was centrifuged for serum separation at approximately 3000 rpm for 15 minutes (11) , the separated sera were used for biochemical tests such as determination of fasting blood glucose. ...
Reference: 218 Medico-legal Update