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

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.

MeSH terms

  • Adult
  • Anti-Mullerian Hormone / genetics*
  • Anti-Mullerian Hormone / metabolism
  • Case-Control Studies
  • Dihydrotestosterone / metabolism
  • Dihydrotestosterone / pharmacology*
  • Estradiol / metabolism
  • Estradiol / pharmacology*
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / genetics
  • Estrogen Receptor beta / metabolism
  • Female
  • Follicular Phase / drug effects
  • Follicular Phase / genetics
  • Follicular Phase / metabolism
  • Gene Expression Regulation / drug effects
  • Granulosa Cells / drug effects
  • Granulosa Cells / metabolism
  • Humans
  • Polycystic Ovary Syndrome / genetics*
  • Polycystic Ovary Syndrome / metabolism
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism
  • Receptors, Peptide / genetics*
  • Receptors, Peptide / metabolism
  • Receptors, Transforming Growth Factor beta / genetics*
  • Receptors, Transforming Growth Factor beta / metabolism
  • Young Adult


  • AR protein, human
  • ESR1 protein, human
  • ESR2 protein, human
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Receptors, Androgen
  • Receptors, Peptide
  • Receptors, Transforming Growth Factor beta
  • anti-Mullerian hormone receptor
  • Dihydrotestosterone
  • Estradiol
  • Anti-Mullerian Hormone