The satiety hormone cholecystokinin gates reproduction in fish by controlling gonadotropin secretion.
Lian Hollander-Cohen, Omer Cohen, Miriam Shulman, Tomer Aiznkot, Pierre Fontanaud, Omer Revah, Patrice Mollard, Matan Golan, Berta Levavi-Sivan
Author Information
Lian Hollander-Cohen: Department of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food, and Environment, Hebrew University of Jerusalem, Rehovot, Israel. ORCID
Omer Cohen: Department of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food, and Environment, Hebrew University of Jerusalem, Rehovot, Israel.
Miriam Shulman: Department of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food, and Environment, Hebrew University of Jerusalem, Rehovot, Israel.
Tomer Aiznkot: Department of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food, and Environment, Hebrew University of Jerusalem, Rehovot, Israel.
Pierre Fontanaud: Institute of Functional Genomics, University of Montpellier, Montpellier, France.
Omer Revah: The Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Patrice Mollard: Institute of Functional Genomics, University of Montpellier, Montpellier, France. ORCID
Matan Golan: Department of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food, and Environment, Hebrew University of Jerusalem, Rehovot, Israel.
Berta Levavi-Sivan: Department of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food, and Environment, Hebrew University of Jerusalem, Rehovot, Israel. ORCID
Life histories of oviparous species dictate high metabolic investment in the process of gonadal development leading to ovulation. In vertebrates, these two distinct processes are controlled by the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH), respectively. While it was suggested that a common secretagogue, gonadotropin-releasing hormone (GnRH), oversees both functions, the generation of loss-of-function fish challenged this view. Here, we reveal that the satiety hormone cholecystokinin (CCK) is the primary regulator of this axis in zebrafish. We found that FSH cells express a CCK receptor, and our findings demonstrate that mutating this receptor results in a severe hindrance to ovarian development. Additionally, it causes a complete shutdown of both gonadotropins secretion. Using in-vivo and ex-vivo calcium imaging of gonadotrophs, we show that GnRH predominantly activates LH cells, whereas FSH cells respond to CCK stimulation, designating CCK as the bona fide FSH secretagogue. These findings indicate that the control of gametogenesis in fish was placed under different neural circuits, that are gated by CCK.
