Novel role for anti-Müllerian hormone in the regulation of GnRH neuron excitability and hormone secretion
Open accessAbstract
Anti-Müllerian hormone (AMH) plays crucial roles in sexual differentiation and gonadal functions. However, the possible extragonadal effects of AMH on the hypothalamic-pituitary-gonadal axis remain unexplored. Here we demonstrate that a significant subset of GnRH neurons both in mice and humans express the AMH receptor, and that AMH potently activates the GnRH neuron firing in mice. Combining in vivo and in vitro experiments, we show that AMH increases GnRH-dependent LH pulsatility and secretion, supporting a central action of AMH on GnRH neurons. Increased LH pulsatility is an important pathophysiological feature in many cases of polycystic ovary syndrome (PCOS), the most common cause of female infertility, in which circulating AMH levels are also often elevated. However, the origin of this dysregulation remains unknown. Our findings raise the intriguing hypothesis that AMH-dependent regulation of GnRH release could be involved in the pathophysiology of fertility and could hold therapeutic potential for treating PCOS.
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AMH levels are higher in anovulatory compared to ovulatory women with PCOS and positively predict symptom severity, including hyperandrogenism and polycystic ovarian morphology.
“AMH levels are higher in anovulatory compared to ovulatory women with PCOS (Cimino et al., 2016) and also positively predict symptom severity, including hyperandrogenism and polycystic ovarian morphology (Garg & Tal, 2016; Sahmay et al., 2014).”
From Endometriosis and polycystic ovary syndrome are diametric disorders (2021) · cites this paper as Cimino et al., 2016
Excessive prenatal AMH exposure could promote the aberrant neuroendocrine function typical of PCOS and AMH can modulate GnRH neuron function.
“These data suggest that excessive prenatal AMH exposure could promote the aberrant neuroendocrine function typical of PCOS and that AMH can modulate GnRH neuron function [37, 38].”
From Polycystic Ovary Syndrome: Pathophysiology, Presentation, and Treatment With Emphasis on Adolescent Girls (2019) · cites this paper as [37]
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“AMH levels are higher in anovulatory compared to ovulatory women with PCOS (Cimino et al., 2016) and also positively predict symptom severity, including hyperandrogenism and polycystic ovarian morphology (Garg & Tal, 2016; Sahmay et al., 2014).”
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- Authors
- Cimino, I., Casoni, F., Liu, X., Messina, A., Parkash, J., Jamin, S. P., Catteau-Jonard, S., Collier, F., Baroncini, M., Dewailly, D., Pigny, P., Prescott, M., Campbell, R., Herbison, A. E., Prevot, V., & Giacobini, P.
- Affiliations
- Inserm (FR)
- University of Otago (NZ)
- Université de Lille (FR)
- Corresponding author
- Giacobini, Paolo
- ORCID
- Venue
- Nature Communications
- Published
- 2016-01-12
- Volume
- 7
- Issue
- 1
- Pages
- 10055-10055
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4729924
- OpenAlex
- W2262780773
- Cited by
- 404
- References
- 67
- Citations by year
- 2026: 31 · 2025: 44 · 2024: 27 · 2023: 41 · 2022: 47 · 2021: 58 · 2020: 38 · 2019: 41 · 2018: 40 · 2017: 23 · 2016: 14
- FWCI
- 52.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- Université de Lille
- Agence Nationale de la Recherche (ANR-09-BLAN-0267, ANR-14-CE12-0015)
- Institut National de la Santé et de la Recherche Médicale (U1172)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- anti-Müllerian hormone, GnRH neurons, GnRH receptor, hypothalamic-pituitary-gonadal axis, luteinizing hormone pulsatility, luteinizing hormone secretion, polycystic ovary syndrome, female infertility, neuronal excitability
- MeSH terms
- Animals, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Follicle Stimulating Hormone, Humans, Hypothalamus, Immunohistochemistry, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Neurons, Polycystic Ovary Syndrome, Rats, Sprague-Dawley, Receptors, Peptide, Receptors, Transforming Growth Factor beta, Reverse Transcriptase Polymerase Chain Reaction, Mice, Anti-Mullerian Hormone, Gene Knock-In Techniques, In Vitro Techniques
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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