Dysregulation of the Anti-Müllerian Hormone System by Steroids in Women With Polycystic Ovary Syndrome

• Published in: The journal of clinical endocrinology and metabolism Vol. 102; no. 11; pp. 3970 - 3978
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.11.2017; Copyright Oxford University Press; Oxford University Press
• Subjects: 17β-Estradiol; Adult; Androgen receptors; Anti-Mullerian Hormone - genetics; Anti-Mullerian Hormone - metabolism; Case-Control Studies; Dihydrotestosterone; Dihydrotestosterone - metabolism; Dihydrotestosterone - pharmacology; DNA-directed RNA polymerase; Down-regulation; Estradiol - metabolism; Estradiol - pharmacology; Estrogen Receptor alpha - genetics; Estrogen Receptor alpha - metabolism; Estrogen Receptor beta - genetics; Estrogen Receptor beta - metabolism; Estrogen receptors; Female; Follicular Phase - drug effects; Follicular Phase - genetics; Follicular Phase - metabolism; Gene expression; Gene Expression Regulation - drug effects; Globulins; Granulosa cells; Granulosa Cells - drug effects; Granulosa Cells - metabolism; Humans; In vitro fertilization; Infertility; Life Sciences; Mass spectroscopy; Other; Ovaries; Patients; Polycystic ovary syndrome; Polycystic Ovary Syndrome - genetics; Polycystic Ovary Syndrome - metabolism; Polymerase chain reaction; Receptors, Androgen - genetics; Receptors, Androgen - metabolism; Receptors, Peptide - genetics; Receptors, Peptide - metabolism; Receptors, Transforming Growth Factor beta - genetics; Receptors, Transforming Growth Factor beta - metabolism; Reproductive Biology; Reverse transcription; Sex hormones; Steroid hormones; Testosterone; Young Adult
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2017-00308

ContextAnti-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.ObjectiveThe 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, PatientsExperiments were performed on follicular fluids (FF) and GCs from women undergoing in vitro fertilization.Main Outcome MeasuresFF steroid levels were measured by mass spectrometry, and messenger RNA (mRNA) accumulation was quantified by reverse transcription real-time polymerase chain reaction.ResultsTotal 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).ConclusionsIn 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.We have studied AMH and AMHR2 regulation by steroids and found that both genes are dysregulated by 5a-DHT and E2 in a way that promotes their overexpression in GCs from PCOS women.