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

Aimar, Pierre; Taieb, Julien; Giton, Frank; Grynberg, Michaël; Touleimat, Salma; Hachem, Hady El; Fanchin, Rénato; Monniaux, Danielle; Cohen‐Tannoudji, Joëlle; Clemente, Nathalie di; Racine, Chrystèle

doi:10.1210/jc.2017-00308

Cited by 54 publications

(50 citation statements)

References 32 publications

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“…We also noticed that in the highest AMH quartile, E 2 levels correlated with AMH only in the PCOS group. In nonpregnant women with PCOS, E 2 has been reported to correlate with AMH both negatively (37) and positively (38), but in most studies no correlation has been detected (24,32,39). Previously an in vitro study demonstrated a lack of E 2 -mediated AMH down-regulation in granulosa cells from women with PCOS (40).…”

Section: Discussionmentioning

confidence: 98%

Circulating antimüllerian hormone and steroid hormone levels remain high in pregnant women with polycystic ovary syndrome at term

Piltonen

Giacobini

Edvinsson

et al. 2019

Fertility and Sterility

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Objective: To investigate plasma antim€ ullerian hormone (AMH) concentration and its relation to steroid hormone levels in pregnant women with polycystic ovary syndrome (PCOS) and controls at term. Design: Case-control study. Setting: University-affiliated hospital. Patient(s): A total of 74 pregnant women at term: 25 women with PCOS (aged 31.6 AE 3.9 years [mean AE standard deviation], body mass index 24.0 AE 3.9 kg/m2, mean gestational length 279 AE 9 days) and 49 controls (aged 31.7 AE 3.3 years, body mass index 24.0 AE 3.3 kg/m2, mean gestational length 281 AE 9 days). Intervention(s): None. Main Outcome Measure(s): Plasma AMH and steroid hormone levels. Result(s): Antim€ ullerian hormone, T, and androstenedione levels were higher in women with PCOS at term compared with controls, whereas estrogen and P levels were similar. The differences were pronounced in women carrying a female fetus. Testosterone and AMH levels correlated positively in both groups, but E 2 levels only in women with PCOS. Conclusion(s): Pregnant women with PCOS present with elevated AMH and androgen levels even at term, suggesting a hormonal imbalance during PCOS pregnancy. Differences were detected especially in pregnancies with a female fetus, raising the question of whether female pregnancies are more susceptible to AMH and steroid hormone actions.

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Section: Discussionmentioning

confidence: 98%

Circulating antimüllerian hormone and steroid hormone levels remain high in pregnant women with polycystic ovary syndrome at term

Piltonen

Giacobini

Edvinsson

et al. 2019

Fertility and Sterility

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“…Treatment with 5-adihydrotestosterone yielded similar results [30]. Furthermore, although estrogens suppress AMH expression, mediated via estrogen receptor b, in normoovulatory women, this suppression was not observed in granulosa cells of anovulatory PCOS women [30,31]. Combined, these results suggest a failure in the downregulation of AMH expression in gonadotropindependent follicular stages in PCOS, which may contribute to a failure in follicular growth.…”

Section: Amh and Its Role In Ovarian Function In Pcosmentioning

confidence: 58%

“…Combined with the elevated LH levels in PCOS, this leads to hyperstimulation of the theca cells and premature luteinization of granulosa cells. Interestingly, LH stimulation increased AMH expression in granulosa cells of PCOS women but not in normoovulatory women [24,29,30]. Treatment with 5-adihydrotestosterone yielded similar results [30].…”

Section: Amh and Its Role In Ovarian Function In Pcosmentioning

confidence: 81%

“…Interestingly, LH stimulation increased AMH expression in granulosa cells of PCOS women but not in normoovulatory women [24,29,30]. Treatment with 5-adihydrotestosterone yielded similar results [30]. Furthermore, although estrogens suppress AMH expression, mediated via estrogen receptor b, in normoovulatory women, this suppression was not observed in granulosa cells of anovulatory PCOS women [30,31].…”

Section: Amh and Its Role In Ovarian Function In Pcosmentioning

confidence: 83%

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AMH in PCOS: Controlling the ovary, placenta, or brain?

Moolhuijsen

Visser

2020

Current Opinion in Endocrine and Metabolic Research

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Polycystic ovary syndrome (PCOS) is a very heterogeneous disease of which the exact pathophysiological mechanisms remain unknown. In PCOS, serum anti-Müllerian hormone (AMH) levels are significantly increased. AMH is a member of the transforming growth factor b family and is expressed by growing follicles in the ovaries. In PCOS, the transcriptional regulation of AMH and AMHR2 is altered, increasing and prolonging its temporal expression pattern. Moreover, the recently discovered extragonadal effects of AMH suggest that there might be a crosstalk between the ovary-placenta-brain. This review summarizes the recent findings concerning AMH and its role in the etiology of PCOS.

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“…A handful of hormones regulating AMHR2 expression have been identified so far, mostly from studies on ovarian tissues. FSH and estradiol were reported to downregulate Amhr2 transcripts in rat ovarian follicles [37], and an inhibitory effect of LH and estradiol on AMHR2 mRNA levels was reported in human luteinized granulosa cells [38, 39]. Contrasting with gonadotropins, bone morphogenetic protein 4 (BMP4) and BMP15 were recently demonstrated to upregulate AMHR2 mRNA levels in human granulosa cells through transcriptional activation of the AMHR2 promoter [40].…”

Section: Introductionmentioning

confidence: 99%

GnRH Transactivates Human AMH Receptor Gene via Egr1 and FOXO1 in Gonadotrope Cells

et al. 2018

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Background/Objectives: Anti-Müllerian hormone (AMH) signaling is critical for sexual differentiation and gonadal function. AMH receptor type 2 (AMHR2) is expressed in extragonadal sites such as brain, and pituitary and emerging evidence indicates that AMH biological action is much broader than initially thought. We recently reported that AMH signaling enhances follicle-stimulating hormone synthesis in pituitary gonadotrope cells. However, mechanisms regulating AMHR2 expression in these extragonadal sites remain to be explored. Method/Results: Here, we demonstrated in perifused murine LβT2 gonadotrope cells that Amhr2 expression is differentially regulated by GnRH pulse frequency with an induction under high GnRH pulsatility. Furthermore, we showed that GnRH transactivates the human AMHR2 promoter in LβT2 cells. Successive deletions of the promoter revealed the importance of a short proximal region (–53/–37 bp) containing an Egr1 binding site. Using site-directed mutagenesis of Egr1 motif and siRNA mediated-knockdown of Egr1, we demonstrated that Egr1 mediates basal and GnRH-dependent activity of the promoter, identifying Egr1 as a new transcription factor controlling hAMHR2 expression. We also showed that SF1 and β-catenin are required for basal promoter activity and demonstrated that both factors contribute to the GnRH stimulatory effect, independently of their respective binding sites. Furthermore, using a constitutively active mutant of FOXO1, we identified FOXO1 as a negative regulator of basal and GnRH-dependent AMHR2 expression in gonadotrope cells. Conclusions: This study identifies GnRH as a regulator of human AMHR2 expression, further highlighting the importance of AMH signaling in the regulation of gonadotrope function.

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

Abstract: 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.

Cited by 54 publications

References 32 publications

Circulating antimüllerian hormone and steroid hormone levels remain high in pregnant women with polycystic ovary syndrome at term

Circulating antimüllerian hormone and steroid hormone levels remain high in pregnant women with polycystic ovary syndrome at term

AMH in PCOS: Controlling the ovary, placenta, or brain?

GnRH Transactivates Human AMH Receptor Gene via Egr1 and FOXO1 in Gonadotrope Cells

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