Folliculogenesis and ovulation in fish are controlled by distinct neuropeptides

Abstract Life histories of oviparous species dictate high metabolic investment in the process of gonadal development culminating in ovulation. 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 models have confounded our view of the role of GnRH in the control of gonadotropins, and particularly FSH, in teleosts. Here, we used in vivo and ex vivo calcium imaging of zebrafish gonadotrophs to study the regulation of gonadotropin release in fish. We show that while LH cells are highly responsive to GnRH stimulation, the response of FSH cells is weak and inconsistent. Furthermore, we found that FSH cells express the receptor for the satiety hormone cholecystokinin (CCK) and display a strong calcium response to its application, accompanied by FSH secretion which designates this peptide as a bona fide FSH secretagogue. However, a degree of overlap exists in the functional potency of GnRH and CCK to activate the two gonadotroph cell types, which is manifested by a complete shutdown of gonadotropin production upon the removal of CCK receptor signalling. From an evolutionary perspective, these findings propose a new way of thinking about the control of fish reproduction, in which the control of folliculogenesis and ovulation in fish were placed under different neural circuits, that are metabolically-gated by a common neuropeptide.