Gonadotropin releasing hormone antagonists suppress aromatase and anti-Müllerian hormone expression in human granulosa cells

Nurit Winkler, Orhan Bukulmez, Daniel B. Hardy, Bruce R. Carr

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Objective: To investigate the effects of a gonadotropin-releasing hormone antagonist (GnRH-ANT) on the expression of anti-Müllerian Hormone (AMH) and aromatase (via the exon CYP19IIa promoter), in cultured human granulosa cells (hGCs) and the human granulosa cell line (HGL5). Design: Primary cell cultures of hGCs and culture of HGL5 cells. Setting: Academic center. Patient(s): Women undergoing IVF because of male factor, tubal infertility, or donor eggs. Intervention(s): hGCs and HGL5 cells were treated with a GnRH-ANT (1 nM and 1 μM) alone or in combination with cAMP (1 mM). Media was collected and stored at -80°C until assayed. Main Outcome Measure(s): mRNA levels of CYP19 IIa, AMH, steroidogenic factor 1 (SF-1) and liver receptor homologue-1 (LRH-1) were determined by quantitative polymerase chain reaction. ELISA was used to determined estradiol (E2) levels in the culture media. Pooled results from triplicate experiments were analyzed using one-way analysis of variance with Student-Newman-Keuls multiple-comparison methods. Result(s): The GnRH-ANT decreased the expressions of CYP19 IIa, AMH, SF-1, and LRH-1. cAMP induced aromatase and AMH expression. Cotreatment with cAMP and GnRH-ANT caused a dose-dependent suppression of AMH and CYP19 IIa mRNA. A GnRH agonist (GnRH-A) increased the mRNA expressions of CYP 19 IIa and AMH. The GnRH-ANT decreased E2 production in cultured hGCs. Conclusion(s): GnRH-ANTs, in addition to their central suppressive effects on the pituitary, may have a direct effect on ovarian granulosa cells with inhibition of aromatase and AMH expression. Furthermore, the inhibitory effect could be mediated via suppression of SF-1 and LRH-1, and may play a role in estrogen-mediated ovarian folliculogenesis.

Original languageEnglish (US)
Pages (from-to)1832-1839
Number of pages8
JournalFertility and Sterility
Volume94
Issue number5
DOIs
StatePublished - Oct 1 2010

Keywords

  • AMH
  • CYP 19 IIa
  • GnRH agonist
  • GnRH analogues
  • GnRH antagonist
  • MIS
  • aromatase

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

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