Dysregulation of the Anti-Müllerian Hormone System by Steroids in Women With Polycystic Ovary Syndrome.
作者信息
Pierre Alice, Taieb Joëlle, Giton Frank, Grynberg Michaël, Touleimat Salma, El Hachem Hady, Fanchin Renato, Monniaux Danielle, Cohen-Tannoudji Joëlle, di Clemente Nathalie, Racine Chrystèle
机构信息
Université Paris Diderot, Sorbonne Paris Cité, F-75013 Paris, France.
Institut National de la Santé et de la Recherche Médicale Unité 1133, Physiologie de l'Axe Gonadotrope, F-75013 Paris, France.
出版信息
J Clin Endocrinol Metab. 2017 Nov 1;102(11):3970-3978. doi: 10.1210/jc.2017-00308.
CONTEXT
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.