Gonadotrophs have a dual origin, with most derived from early postnatal pituitary stem cells

Abstract Gonadotrophs are the essential pituitary endocrine cells for reproduction. They produce both luteinizing (LH) and follicle-stimulating (FSH) hormones that act on the gonads to promote germ cell maturation and steroidogenesis. Their secretion is controlled by the hypothalamic gonadotrophin-r...

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Main Authors: Daniel Sheridan, Probir Chakravarty, Gil Golan, Yiolanda Shiakola, Jessica Olsen, Elise Burnett, Christophe Galichet, Tatiana Fiordelisio, Patrice Mollard, Philippa Melamed, Robin Lovell-Badge, Karine Rizzoti
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59495-7
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author Daniel Sheridan
Probir Chakravarty
Gil Golan
Yiolanda Shiakola
Jessica Olsen
Elise Burnett
Christophe Galichet
Tatiana Fiordelisio
Patrice Mollard
Philippa Melamed
Robin Lovell-Badge
Karine Rizzoti
author_facet Daniel Sheridan
Probir Chakravarty
Gil Golan
Yiolanda Shiakola
Jessica Olsen
Elise Burnett
Christophe Galichet
Tatiana Fiordelisio
Patrice Mollard
Philippa Melamed
Robin Lovell-Badge
Karine Rizzoti
author_sort Daniel Sheridan
collection DOAJ
description Abstract Gonadotrophs are the essential pituitary endocrine cells for reproduction. They produce both luteinizing (LH) and follicle-stimulating (FSH) hormones that act on the gonads to promote germ cell maturation and steroidogenesis. Their secretion is controlled by the hypothalamic gonadotrophin-releasing hormone (GnRH), and gonadal steroid feedback. Gonadotrophs first appear in the embryonic pituitary, along with other endocrine cell types, and all expand after birth. While gonadotrophs may display heterogeneity in their response to GnRH, they appear, at least transcriptionally, as a homogenous population. The pituitary also contains a population of stem cells (SCs), whose contribution to postnatal growth is unclear, in part because endocrine cells maintain the ability to proliferate. Here we show an unsuspected dual origin of the murine adult gonadotroph population, with most gonadotrophs originating from postnatal pituitary stem cells starting early postnatally and up to puberty, while embryonic gonadotrophs are maintained. We further demonstrate that postnatal gonadotroph differentiation happens independently of gonadal signals and is not affected by impairment of GnRH signalling. The division of gonadotrophs based on separate origins has implications for our understanding of the establishment and regulation of reproductive functions, both in health and in disease.
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spelling doaj-art-54bad160fff74cb49db5dbe083da18922025-08-20T03:08:43ZengNature PortfolioNature Communications2041-17232025-05-0116111310.1038/s41467-025-59495-7Gonadotrophs have a dual origin, with most derived from early postnatal pituitary stem cellsDaniel Sheridan0Probir Chakravarty1Gil Golan2Yiolanda Shiakola3Jessica Olsen4Elise Burnett5Christophe Galichet6Tatiana Fiordelisio7Patrice Mollard8Philippa Melamed9Robin Lovell-Badge10Karine Rizzoti11Laboratory of Stem Cell Biology and Developmental Genetics, The Francis Crick InstituteBioinformatics core, The Francis Crick InstituteFaculty of Biology, Technion Israel Institute of TechnologyLaboratory of Stem Cell Biology and Developmental Genetics, The Francis Crick InstituteGenetic Modification Service, The Francis Crick InstituteLaboratory of Stem Cell Biology and Developmental Genetics, The Francis Crick InstituteLaboratory of Stem Cell Biology and Developmental Genetics, The Francis Crick InstituteLaboratorio de Neuroendocrinologia Comparada, Laboratorio Nacional de Soluciones Biomimeticas para Diagnostico y Terapia, Universidad Nacional Autonoma de MexicoInstitut de Génomique Fonctionnelle, University of Montpellier, CNRS, InsermFaculty of Biology, Technion Israel Institute of TechnologyLaboratory of Stem Cell Biology and Developmental Genetics, The Francis Crick InstituteLaboratory of Stem Cell Biology and Developmental Genetics, The Francis Crick InstituteAbstract Gonadotrophs are the essential pituitary endocrine cells for reproduction. They produce both luteinizing (LH) and follicle-stimulating (FSH) hormones that act on the gonads to promote germ cell maturation and steroidogenesis. Their secretion is controlled by the hypothalamic gonadotrophin-releasing hormone (GnRH), and gonadal steroid feedback. Gonadotrophs first appear in the embryonic pituitary, along with other endocrine cell types, and all expand after birth. While gonadotrophs may display heterogeneity in their response to GnRH, they appear, at least transcriptionally, as a homogenous population. The pituitary also contains a population of stem cells (SCs), whose contribution to postnatal growth is unclear, in part because endocrine cells maintain the ability to proliferate. Here we show an unsuspected dual origin of the murine adult gonadotroph population, with most gonadotrophs originating from postnatal pituitary stem cells starting early postnatally and up to puberty, while embryonic gonadotrophs are maintained. We further demonstrate that postnatal gonadotroph differentiation happens independently of gonadal signals and is not affected by impairment of GnRH signalling. The division of gonadotrophs based on separate origins has implications for our understanding of the establishment and regulation of reproductive functions, both in health and in disease.https://doi.org/10.1038/s41467-025-59495-7
spellingShingle Daniel Sheridan
Probir Chakravarty
Gil Golan
Yiolanda Shiakola
Jessica Olsen
Elise Burnett
Christophe Galichet
Tatiana Fiordelisio
Patrice Mollard
Philippa Melamed
Robin Lovell-Badge
Karine Rizzoti
Gonadotrophs have a dual origin, with most derived from early postnatal pituitary stem cells
Nature Communications
title Gonadotrophs have a dual origin, with most derived from early postnatal pituitary stem cells
title_full Gonadotrophs have a dual origin, with most derived from early postnatal pituitary stem cells
title_fullStr Gonadotrophs have a dual origin, with most derived from early postnatal pituitary stem cells
title_full_unstemmed Gonadotrophs have a dual origin, with most derived from early postnatal pituitary stem cells
title_short Gonadotrophs have a dual origin, with most derived from early postnatal pituitary stem cells
title_sort gonadotrophs have a dual origin with most derived from early postnatal pituitary stem cells
url https://doi.org/10.1038/s41467-025-59495-7
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