Dysregulation of the Anti-Müllerian Hormone System by Steroids in Women With Polycystic Ovary Syndrome
Anti-Müllerian hormone (AMH) and AMH type II receptor (AMHR2) are overexpressed in granulosa cells (GCs) from women with polycystic ovary syndrome (PCOS), the most common cause of female infertility.Objective:
The aim of the study was to compare the regulation of the AMH/AMHR2 system by 5α-dihydrotestosterone (5α-DHT) and estradiol (E2) in GCs from control subjects and women with PCOS.Design, Setting, Patients:
Experiments were performed on follicular fluids (FF) and GCs from women undergoing in vitro fertilization.Main Outcome Measures:
FF steroid levels were measured by mass spectrometry, and messenger RNA (mRNA) accumulation was quantified by reverse transcription real-time polymerase chain reaction.Results:
Total testosterone (T), free T, and 5α-DHT FF levels were significantly higher (P < 0.001) in women with PCOS than in controls. However, E2 and sex hormone-binding globulin concentrations were comparable between the two groups. In GCs from control women, the AMH and AMHR2 expression were not affected by 5α-DHT treatment, whereas AMH mRNA levels were upregulated by 5α-DHT in GCs from patients with PCOS (2.3-fold, P < 0.01) overexpressing the androgen receptor (1.4-fold, P < 0.05). E2 downregulated the AMH and AMHR2 expression in GCs from control women (1.4-fold, P < 0.001 and 1.8-fold, P < 0.01, respectively) but had no effect on these genes in GCs from women with PCOS. This differential effect of E2 was associated with a higher estrogen receptor 1 expression in GCs from women with PCOS (1.9-fold, P < 0.05).Conclusions:
In GCs from women with PCOS, the regulation of AMH and AMHR2 expression is altered in a way that promotes the overexpression of the AMH/AMHR2 system, and could contribute to the follicular arrest observed in these patients.