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 language | English (US) |
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Pages (from-to) | 1832-1839 |
Number of pages | 8 |
Journal | Fertility and sterility |
Volume | 94 |
Issue number | 5 |
DOIs | |
State | Published - Oct 2010 |
Keywords
- AMH
- CYP 19 IIa
- GnRH agonist
- GnRH analogues
- GnRH antagonist
- MIS
- aromatase
ASJC Scopus subject areas
- Reproductive Medicine
- Obstetrics and Gynecology