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

Daniel Sheridan, Probir Chakravarty, Gil Golan, Yiolanda Shiakola, Jessica Olsen, Elise Burnett, Christophe Galichet, Tatiana Fiordelisio, Patrice Mollard, Philippa Melamed, Robin Lovell-Badge () and Karine Rizzoti ()
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Daniel Sheridan: The Francis Crick Institute
Probir Chakravarty: The Francis Crick Institute
Gil Golan: Technion Israel Institute of Technology
Yiolanda Shiakola: The Francis Crick Institute
Jessica Olsen: The Francis Crick Institute
Elise Burnett: The Francis Crick Institute
Christophe Galichet: The Francis Crick Institute
Tatiana Fiordelisio: Universidad Nacional Autonoma de Mexico
Patrice Mollard: Inserm
Philippa Melamed: Technion Israel Institute of Technology
Robin Lovell-Badge: The Francis Crick Institute
Karine Rizzoti: The Francis Crick Institute

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-59495-7

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