title: Elevated expression of steroidogenesis pathway genes; CYP17, GATA6 and StAR in prenatally androgenized rats.
abstract: It is believed that excess androgen exposure of the fetus, via altered gene expression, causes hyperandrogenism a key feature of polycystic ovary syndrome (PCOS). The aim of this study was to evaluate expression of Cytochrome P450-17 (CYP17), GATA-binding protein (GAGT6) and Steroidogenic acute regulatory protein (StAR), genes of adult female rats prenatally exposed to androgen excess, closely reflect endocrine and ovarian disturbances of PCOS in women, by comparing them during different phases of estrus cycle with those of non-treated rats. Both the adult prenatally testosterone exposed and control rats (n=23, each) were divided into four groups based on their observed vaginal smear (proestrus, estrus, metestrus and diestrus) and the relative expression of CYP17, GATA6 and StAR genes was measured in ovarian theca cells using Cyber-green Real-Time PCR. Serum sex steroid hormones and gonadotropins levels were measured using the ELISA method; a comparison of these two groups showed that there was an overall increase in the studied genes (CYP17; 2.39 fold change, 95% CI: 1.23-3.55; P<0.05, GATA6; 2.08 fold change, 95% CI: 1.62-2.55; P<0.0001, and StAR; 1.4 fold change, 95% CI: 1.02-1.78; P<0.05), despite variations in different phases with maximum elevation for all genes in diestrus. The changes observed may impair the normal development of ovaries that mediate the programming of adult PCOS.
authors: Cellular and Molecular Endocrine Research Center and Obesity Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Sciences, Tehran, Iran; Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: marziah.salehi@gmail.com.
authors: Marziyeh Salehi
authors: MS
authors: Jahromi
authors: Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: ramezani@endocrine.ac.ir.
authors: Fahimeh Ramezani
authors: FR
authors: Tehrani
authors: Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: mahsa_asal82@yahoo.com.
authors: Mahsa
authors: M
authors: Noroozzadeh
authors: Cellular and Molecular Endocrine Research Center and Obesity Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: zarkesh1388@gmail.com.
authors: Maryam
authors: M
authors: Zarkesh
authors: Endocrine Physiology Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: ghasemi@endocrine.ac.ir.
authors: Asghar
authors: A
authors: Ghasemi
authors: Cellular and Molecular Endocrine Research Center and Obesity Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: azitavakili@endocrine.ac.ir.
authors: Azita
authors: A
authors: Zadeh-Vakili
mesh_terms: D000728:Androgens / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D005260:Female; D050993:GATA6 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D010750:Phosphoproteins / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D013254:Steroid 17-alpha-Hydroxylase / Q000096:biosynthesis* / Q000235:genetics; D014770:Virilism / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D000728:Androgens; D050993:GATA6 Transcription Factor; C084364:Gata6 protein, rat; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D013254:Steroid 17-alpha-Hydroxylase
keywords: CYP17; GATA6; Gene expression; PCOS; Prenatal androgen excess; Rat model; StAR