Upregulation of human chorionic gonadotrophin-induced steroidogenic acute regulatory protein by insulin-like growth factor-I in rat Leydig cells
ABSTRACT Insulin-like growth factor-I (IGF-I) plays an essential role in reproductive function. Leydig cells express specific IGF-I receptors, and IGF-I enhances human chorionic gonadorphin (hCG)-induced testosterone formation. In the present study, we evaluate the effect of IGF-I on the gene expression and protein levels of steroidogenic acute regulatory protein (StAR), the rate-limiting step in steroidogenesis. StAR mRNA is expressed in rat Leydig cells as two major transcripts of 3.8 and 1.7 kb. StAR mRNA levels (both 3.8 and 1.7 kb) were markedly induced about 20-fold by hCG (10 ng/mL). Concomitant addition of IGF-I (50 or 100 ng/mL) and hCG (10 ng/mL) resulted in significant increases in StAR and cytochrome P450 side-chain cleavage (P450scc) mRNA levels, whereas lower doses of IGF-I (1 or 10 ng/ mL) had small effects. Synergistic effects of IGF-I and hCG on StAR mRNA levels were confirmed by ribonuclease protection assay (RPA). IGF-I (100 ng/mL) enhanced hCG- and 20 OH-cholesterol + hCG-induced testosterone formation, whereas the conversions of pregnenolone, 17-OH pregnenolone, dehydroepiandrosterone, and androstenedione to testosterone were not affected. This suggests that the major effect of IGF-I is at the steps of StAR and P450scc, whereas other steroidogenic enzymes are not affected. To evaluate whether increased StAR mRNA levels induced by IGF-I and hCG are associated with increased StAR protein levels, we carried out Western blot analyses. Basal StAR protein levels were low after 24 h in culture. hCG (10 ng/mL) increased StAR protein by 4.5-fold. In the presence of IGF-I (100 ng/mL), hCG-induced StAR protein levels were further increased. In conclusion, our present study demonstrated that IGF-I enhances Leydig cell steroidogenesis by upregulating hCG-induced StAR gene expression and protein production.
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ABSTRACT: Nanomaterials (NMs) are engineered for commercial purposes such as semiconductors, building materials, cosmetics, and drug carriers, while natural nanoparticles (NPs) already exist in the environment. Due to their unique physicochemical properties, they may interact actively with biological systems. Some of these interactions might be detrimental to human health, and therefore studies on the potential 'nanotoxicity' of these materials in different organ systems are warranted. The purpose of developing the concept of nanotoxicity is to recognize and evaluate the hazards and risks of NMs and evaluate safety. This review will summarize and discuss recent reports derived from cell lines or animal models concerning the effects of NMs on, and their application in, the endocrine system of mammalian and other species. It will present an update on current studies of the effects of some typical NMs-such as metal-based NMs, carbon-based NMs, and dendrimers-on endocrine functions, in which some effects are adverse or unwanted and others are favorable or intended. Disruption of endocrine function is associated with adverse health outcomes including reproductive failure, metabolic syndrome, and some types of cancer. Further investigations are therefore required to obtain a thorough understanding of any potential risk of pathological endocrine disruption from products containing NMs. This review aims to provide impetus for further studies on the interactions of NMs with endocrine functions.Small 05/2013; 9(9-10). DOI:10.1002/smll.201201517 · 7.51 Impact Factor
Article: Regulation by Adrenocorticotropin (ACTH), Angiotensin II, Transforming Growth Factor , and Insulin-Like Growth Factor I of Bovine Adrenal Cell Steroidogenic Capacity and Expression of ACTH Receptor, Steroidogenic Acute Regulatory Protein, Cytochrome P450c17, and 3 -Hydroxysteroid Dehydrogenase[Show abstract] [Hide abstract]
ABSTRACT: The purpose of this study was to evaluate the time-course effect of a 36-h treatment with ACTH (1028 M), transforming growth factor-b1 (TGFb1; 10210 M), angiotensin II (AngII; 1027 M), and insulin-like growth factor I (IGF-I; 1028 M) on the steroidogenic capacity of bovine adrenocortical cells (BAC) and on messenger RNA (mRNA) levels of ACTH receptor, cytochrome P450c17, 3b-hydroxysteroid dehydroge- nase (3bHSD), steroidogenic acute regulatory protein (StAR), and StAR protein. ACTH and IGF-I enhanced, in a time-dependent man- ner, the acute 2-h ACTH-induced cortisol production, whereas TGFb1 and AngII markedly reduced it. ACTH, IGF-I, and AngII increased ACTH receptor mRNA, but the opposite was observed after TGFb1 treatment. ACTH and IGF-I increased P450c17 and 3bHSD mRNAs, whereas AngII and TGFb1 had the opposite effects. However, the effects of the four peptides on ACTH-induced cortisol production ap- peared before any significant alterations of the mRNA levels occurred. The most marked and rapid effect of the four peptides was on StAR mRNA. The stimulatory effect of ACTH was seen within 1.5 h, peaked at 4 - 6 h, and declined thereafter, but at the end of the 36-h pre- treatment, the levels of StAR mRNA and protein were higher than those in control cells. IGF-I also enhanced StAR mRNA levels within 1.5 h, and these levels remained fairly constant. The effects of AngII on StAR mRNA expression were biphasic, with a peak within 1.5-3 h, followed by a rapid decline to almost undetectable levels of both mRNA and protein. TGFb1 had no significant effect during the first 3 h, but thereafter StAR mRNA declined, and at the end of the experiment the StAR mRNA and protein were almost undetectable. Similar results were observed when cells were treated with ACTH plus TGFb1. A 2-h acute ACTH stimulation at the end of the 36-h pretreatment caused a higher increase in StAR mRNA and protein in ACTH- or IGF-I-pretreated cells than in control cells, which, in turn, had higher levels than cells pretreated with TGFb1, ACTH plus TGFb1, or AngII. These results and the fact that the stimulatory (IGF-I) or inhibitory (AngII and TGFb1) effects on ACTH-induced cortisol production were more pronounced than those on the ability of cells to transform preg- nenolone into cortisol strongly suggest that regulation of StAR ex- pression is one of the main factors, but not the only one, involved in the positive (IGF-I) or negative (TGFb1 and AngII) regulation of BAC for ACTH steroidogenic responsiveness. A high correlation between steady state mRNA level and acute ACTH-induced cortisol production favors this conclusion. (Endocrinology 141: 1599 -1607, 2000)Endocrinology 05/2000; 141(5):1599-1607. DOI:10.1210/en.141.5.1599 · 4.72 Impact Factor
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ABSTRACT: The biosynthesis of steroid hormones is necessary to maintain reproductive functions and body homeostasis. This process, which is carried out in acutely and chronically regulated steroidogenic tissues, depends on the activation of signaling pathways particularly mediated by the cyclic adenosine monophosphate dependent protein kinase (PKA). Data obtained by our and other groups in human placenta and other tissues, have clearly showed that dynamic phosphorylation catalyzed by PKA is related to steroidogenesis, including its hormonal regulation. it is known, however, that this process also involves the participation of other PKA independent signaling cascades, which are activated by trophic hormones, cytokines or growth factors and others such as calcium, chloride ions and arachidonic acid metabolites. The understanding of the stimulating factors, as well as the mechanisms that regulate the synthesis of steroid hormones, will allow us the identification of potential intervention sites that may contribute to maintain body homeostasis and different functions depending on them.06/2012; 15(1):24-36.