Expression of genes controlling steroid metabolism and action in granulosa-lutein cells of women with polycystic ovaries

Mol Cell Endocrinol. 2019 Apr 15:486:47-54. doi: 10.1016/j.mce.2019.02.015. Epub 2019 Feb 22.

Abstract

Introduction: Aberrant function of granulosa cells has been implicated in the pathophysiology of PCOS.

Materials & methods: Granulosa lutein (GL) cells were collected during oocyte retrieval for IVF/ICSI. RT-qPCR was used to compare gene expression between 12 control women, 12 with ovulatory PCO and 12 with anovulatory PCOS. To examine which genes are directly regulated by androgens, GL cells from an additional 12 control women were treated in-vitro with 10 nM dihydrotestosterone (DHT).

Results: GL cells from women with PCOS showed reduced expression of CYP11A1 3-fold (p = 0.005), HSD17B1 1.8-fold (p = 0.02) and increased expression of SULT1E1 7-fold (p = 0.0003). Similar results were seen in ovulatory women with PCO. GL cells treated with 10 nM DHT showed a 4-fold (p = 0.03) increase in expression of SULT1E1 and a 5-fold reduction in SRD5A1 (p = 0.03).

Conclusions: These findings support the notion that aberrant regulation of steroid metabolism or action play a part in ovarian dysfunction in PCOS.

Keywords: Granulosa cells; PCOS; Steroidogenic enzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Androgens / pharmacology
  • Body Mass Index
  • Cells, Cultured
  • Dihydrotestosterone / pharmacology
  • Estradiol / metabolism
  • Female
  • Follicle Stimulating Hormone / pharmacology
  • Gene Expression Regulation* / drug effects
  • Gene Regulatory Networks
  • Granulosa Cells / drug effects
  • Granulosa Cells / metabolism*
  • Humans
  • In Vitro Oocyte Maturation Techniques
  • Luteal Cells / drug effects
  • Luteal Cells / metabolism*
  • Models, Biological
  • Ovulation / genetics
  • Polycystic Ovary Syndrome / genetics*
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Reference Standards
  • Steroids / metabolism*

Substances

  • Androgens
  • Receptors, Estrogen
  • Steroids
  • Dihydrotestosterone
  • Estradiol
  • Follicle Stimulating Hormone