Identification of the FSH-RH as the other gonadotropin-releasing hormone

Shun Kenny Uehara, Yuji Nishiike, Kazuki Maeda, Tomomi Karigo, Shigehiro Kuraku, Kataaki Okubo and Shinji Kanda ()
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Shun Kenny Uehara: The University of Tokyo
Yuji Nishiike: The University of Tokyo
Kazuki Maeda: The University of Tokyo
Tomomi Karigo: Johns Hopkins University School of Medicine
Shigehiro Kuraku: RIKEN Center for Biosystems Dynamics Research
Kataaki Okubo: The University of Tokyo
Shinji Kanda: The University of Tokyo

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract In vertebrates, folliculogenesis and ovulation are regulated by two distinct pituitary gonadotropins: follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Currently, there is an intriguing consensus that a single hypothalamic neurohormone, gonadotropin-releasing hormone (GnRH), regulates the secretion of both FSH and LH, although the required timing and functions of FSH and LH are different. However, recent studies in many non-mammalian vertebrates indicated that GnRH is dispensable for FSH function. Here, by using medaka as a model teleost, we successfully identify cholecystokinin as the other gonadotropin regulator, FSH-releasing hormone (FSH-RH). Our histological and in vitro analyses demonstrate that hypothalamic cholecystokinin-expressing neurons directly affect FSH cells through the cholecystokinin receptor, Cck2rb, thereby increasing the expression and release of FSH. Remarkably, the knockout of this pathway minimizes FSH expression and results in a failure of folliculogenesis. Here, we propose the existence of the “dual GnRH model” in vertebrates that utilize both FSH-RH and LH-RH.

Date: 2024
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DOI: 10.1038/s41467-024-49564-8

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