The anti-Müllerian hormone (AMH) acts as a gatekeeper of ovarian steroidogenesis inhibiting the granulosa cell response to both FSH and LH

Sacchi, Sandro; D’Ippolito, Giovanni; Sena, Paola; Marsella, Tiziana; Tagliasacchi, Daniela; Maggi, E.; Argento, Cindy; Tirelli, Alessandra; Giulini, Simone; Marca, Antonio La

doi:10.1007/s10815-015-0615-y

Cited by 78 publications

(55 citation statements)

References 22 publications

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“…In the infantile ovary, our findings showed that AMH treatment significantly repressed FSH-mediated induction of Cyp19a1 aromatase, as previously described for human luteinized granulosa cells in vitro (Grossman et al 2008, Chang et al 2013, Prapa et al 2015, Sacchi et al 2016. This effect unlikely resulted from decreased FSHR expression as described in human tumoral granulosa cells (Pellatt et al 2011), since AMH did not alter Fshr transcript abundance, albeit we cannot exclude that it could have affected FSHR protein levels.…”

Section: :2supporting

confidence: 85%

“…The present study reveals that FSH represses Amh expression specifically in the first follicular waves, wherein we previously showed that FSH induces a consistent Cyp19a1 aromatase expression without altering that of Ccnd2 (François et al 2017). Since other studies reported that AMH prevents FSH-induced E2 synthesis (Grossman et al 2008, Chang et al 2013, Prapa et al 2015, Sacchi et al 2016, possibly by down-regulating FSHR expression (Pellatt et al 2011), and that it regulates FSH-mediated follicular growth (McGee et al 1997, Durlinger et al 2001, we next sought to investigate whether the observed decrease in Amh expression could facilitate FSH-mediated Cyp19a1 expression and explain the loss of FSH-mediated Ccnd2 expression in preantral/early antral follicles. We therefore tested the effect of a treatment by AMH on the expression of Cyp19a1, Fshr and Ccnd2 in the infantile ovary.…”

Section: Amh Prevents Fsh-mediated Induction Of Cyp19a1 Aromatase Witsupporting

confidence: 57%

“…These data have led to the idea that AMH inhibits the recruitment of primordial follicles. Additional in vivo and in vitro studies have indicated that AMH may keep follicles insensitive to FSH-dependent growth (Durlinger et al 2001) and to FSH-mediated steroidogenesis by inhibiting the expression and activity of aromatase (Grossman et al 2008, Chang et al 2013, Prapa et al 2015, Sacchi et al 2016. Hence, in growing follicles from adult cyclic females, the loss of AMH expression would allow FSHdependent growth and subsequent maturation associated with E2 synthesis (Visser & Themmen 2014).…”

Section: Introductionmentioning

confidence: 99%

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FSH inhibits AMH to support ovarian estradiol synthesis in infantile mice

Devillers

Petit

Cluzet

et al. 2019

Journal of Endocrinology

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Anti-Müllerian hormone (AMH) regulates ovarian function in cyclic females, notably by preventing premature follicle-stimulating hormone (FSH)-mediated follicular growth and steroidogenesis. Its expression in growing follicles is controlled by FSH and by estradiol (E2). In infantile females, there is a transient increase in the activity of the gonadotrope axis, as reflected by elevated levels of both gonadotropins and E2. We previously demonstrated in mice that elevated FSH concentrations are necessary to induce E2 production by preantral/early antral follicles through the stimulation of aromatase expression without supporting their growth. However, whether this action of FSH could involve AMH is unknown. Here, we show that Amh mRNA and protein abundance and serum AMH levels are elevated in infantile mouse females, compared with those in adults. By experimentally manipulating FSH and E2 levels in infantile mice, we demonstrate that high FSH concentrations lower Amh expression specifically in preantral/early antral follicles, whereas E2 has no effect. Importantly, treatment of infantile ovaries in organotypic cultures with AMH decreases FSH-mediated expression of Cyp19a1 aromatase, but it does not alter the expression of cyclin D2-mediating granulosa cell proliferation. Overall, our data indicate that the infantile elevation in FSH levels suppresses Amh expression in preantral/early antral follicles, thereby favoring Cyp19a1 aromatase expression and E2 production. Together with recent discoveries that AMH can act on both the hypothalamus and the pituitary to increase gonadotropin levels, this work suggests that AMH is a critical regulator of the gonadotrope axis during the infantile period, thereby contributing to adult reproductive function programming.

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Section: :2supporting

confidence: 85%

Section: Amh Prevents Fsh-mediated Induction Of Cyp19a1 Aromatase Witsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

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FSH inhibits AMH to support ovarian estradiol synthesis in infantile mice

Devillers

Petit

Cluzet

et al. 2019

Journal of Endocrinology

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“…In fetal development, AMH prevents development of the Müllerian ducts during male sex differentiation . In addition, AMH plays an important role in ovarian function and folliculogenesis, modulating ovarian sensitivity to gonadotropins, and in gene expression, leading to production of ovarian steroids . Anti‐Müllerian hormone is a well‐described biomarker of ovarian reserve and has been used to predict age‐at‐menopause and primary ovarian insufficiency .…”

Section: Introductionmentioning

confidence: 99%

A pilot longitudinal study of anti‐Müllerian hormone levels throughout gestation in low risk pregnancy

Freeman

Whitcomb

Roy

et al. 2018

Health Science Reports

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Background: Anti-Mϋllerian hormone (AMH) plays an important role regulating ovarian sensitivity to follicle-stimulating hormone and luteinizing hormone in folliculogenesis. Anti-Mϋllerian hormone is well established as a biomarker of ovarian reserve but may also have utility in predicting pregnancy outcomes. Few studies have described AMH levels in pregnancy and, among those that have, most have used cross-sectional study designs and are limited to participants seeking fertility treatment. Our aim was to analyze AMH longitudinally in low-risk pregnancies. Methods:We conducted a prospective cohort study at Baystate Medical Center, a large tertiary care hospital in Springfield, MA, USA. We recruited women (n = 30) with low risk, singleton pregnancies, aged 18 to 35 years, with BMI between 18 and 40 kg/ m 2 , and without preexisting disease. Anti-Mϋllerian hormone (pmol/L) was measured in plasma samples collected at 5 prenatal care visits throughout gestation.Results: Anti-Mϋllerian hormone levels varied significantly over gestation (Friedman's analysis of variance, P value < .0001). At gestational weeks 7 to 10, average AMH was 36.7 pmol/L (standard error = 8.1) and at weeks 34 to 37 was 9.5 pmol/L (standard error = 1.9). Initial AMH varied between women, and an overall significant log-linear decline was observed.Conclusions: Anti-Mϋllerian hormone varies between women and declines exponentially during pregnancy. The biological mechanism of the heterogeneity of AMH decline over gestation is unclear. Future studies evaluating AMH throughout pregnancy that also assess gravid health and pregnancy outcomes are warranted. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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“…Nevertheless, it is also possible that male signaling mediated by amh ( amhy and/or amha ) suffices to override this cyp19a1a -dependent, developmentally programmed ovarian differentiation. In fact, AMH has suppressive effects on aromatase in other vertebrates (e.g., human granulosa lutein cells) [Grossman et al, 2008;Sacchi et al, 2016]. This would explain the absence of cyp19a1a expression in some XY and XX individuals with amh expression but no apoptosis.…”

mentioning

confidence: 99%

Spatiotemporal Correlations between amh and cyp19a1a Transcript Expression and Apoptosis during Gonadal Sex Differentiation of Pejerrey, Odontesthes bonariensis

Sarida

Zhang

Yamamoto

et al. 2019

Sex Dev

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Sex determination in pejerrey is genetically prescribed by the Y chromosome-linked anti-müllerian hormone amhy but is also strongly influenced by water temperature during the critical period of sex determination. Its gonadal differentiation is characterized by a cephalocaudal and left-to-right histological gradient in both sexes that presumably helps prevent discrepant intersex development in different regions of the gonads in response to ambiguous thermal and genetic stimuli, but the relation of this gradient to molecular processes of sex differentiation is unknown. In this study, we investigated the spatiotemporal expression patterns of amh, gonadal aromatase (cyp19a1a), and apoptosis in relation to the histological gradient in ovaries and testes at an intermediate, sexually neutral temperature. The location and timing of expression of amh, cyp19a1a, and apoptosis seemed to be highly coordinated with the time of gonadal sex differentiation and the histological gradient of gonadal sex differentiation. Apoptosis occurred predominantly in the anterior region of the right gonads and is surmised to be a process to delay differentiation in this area compared to the left gonad, possibly as a means to ensure uniform development in both gonads. Aromatase expression early during development was noted even in putative XY males, supporting the notion of primacy of female development in pejerrey gonads. Thus, apoptosis may be particularly important to prevent discrepant gonadal differentiation in XY individuals where genetic pro-male (amhy), pro-female (cyp19a1a), and thermal stimuli may antagonize.

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The anti-Müllerian hormone (AMH) acts as a gatekeeper of ovarian steroidogenesis inhibiting the granulosa cell response to both FSH and LH

Cited by 78 publications

References 22 publications

FSH inhibits AMH to support ovarian estradiol synthesis in infantile mice

FSH inhibits AMH to support ovarian estradiol synthesis in infantile mice

A pilot longitudinal study of anti‐Müllerian hormone levels throughout gestation in low risk pregnancy

Spatiotemporal Correlations between<b><i> amh</i></b> and <b><i>cyp19a1a</i></b> Transcript Expression and Apoptosis during Gonadal Sex Differentiation of Pejerrey, <b><i>Odontesthes bonariensis</i></b>

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