Research Scientist The Francis Crick Institute, United Kingdom
Abstract: Reproductive health is crucial for fertility, and important for overall well-being. While reproductive capacity begins at puberty, reproductive development starts much earlier, shortly after birth, during a preparatory phase called minipuberty. This period is important for future fertility in males, and brain development in both sexes. The same hormones, control minipuberty, puberty, and reproduction. These hormones, namely LH (luteinizing hormone) and FSH (follicle-stimulating hormone) are produced by the pituitary, a crucial gland located underneath the brain. They act on the gonads where they induce steroidogenesis and the production of germ cells, as well as sexual development, bone strength and physical and psychological health. In turn, LH and FSH synthesis and secretion are controlled by the hypothalamic gonadotrophin-releasing hormone (GnRH), and gonadal steroid feedback. In the pituitary, LH and FSH are produced by gonadotrophs. These first appear in the embryonic pituitary, along other endocrine 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) [1-3], whose contribution to postnatal growth is unclear, in part because endocrine cells maintain the ability to proliferate [4]. 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, as a locally distinct population [5]. We further demonstrate that postnatal gonadotroph differentiation happens independently of GnRH or gonadal signals. 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.
1. T. Fauquier, K. Rizzoti, M. Dattani, R. Lovell-Badge, I. C. Robinson, PNAS (2008). 2. K. Rizzoti, H. Akiyama, R. Lovell-Badge, Cell Stem Cell (2013). 3. K. Rizzoti, P. Chakravarty, D. Sheridan, R. Lovell-Badge, Sci Adv (2023). 4. D. Langlais, C. Couture, M. Kmita, J. Drouin. Mol Endocrinol (2013). 5. D. Sheridan et al., Biorxiv (2024).
Funding Source: Medical Research Council, UK (U117512772, U117562207, and U117570590) and the Francis Crick Institute (FC001107), which receives its core funding from Cancer Research UK, the UK Medical Research Council , and the Wellcome Trust.
