Elevated expression of steroidogenesis pathway genes; CYP17, GATA6 and StAR in prenatally androgenized rats

Gene. 2016 Nov 15;593(1):167-171. doi: 10.1016/j.gene.2016.07.067. Epub 2016 Aug 7.

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.

Keywords: CYP17; GATA6; Gene expression; PCOS; Prenatal androgen excess; Rat model; StAR.

MeSH terms

  • Androgens / adverse effects*
  • Androgens / pharmacology
  • Animals
  • Female
  • GATA6 Transcription Factor / biosynthesis*
  • GATA6 Transcription Factor / genetics
  • Gene Expression Regulation / drug effects*
  • Male
  • Phosphoproteins / chemical synthesis
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Polycystic Ovary Syndrome / genetics
  • Polycystic Ovary Syndrome / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Rats
  • Steroid 17-alpha-Hydroxylase / biosynthesis*
  • Steroid 17-alpha-Hydroxylase / genetics
  • Virilism / chemically induced
  • Virilism / genetics
  • Virilism / metabolism*

Substances

  • Androgens
  • GATA6 Transcription Factor
  • Gata6 protein, rat
  • Phosphoproteins
  • steroidogenic acute regulatory protein
  • Steroid 17-alpha-Hydroxylase