Recent studies of LPXRFa receptor signaling in fish and other vertebrates.

The hypothalamo-pituitary-gonadal (HPG) axis plays a major role in coordinating the reproduction of fish and other vertebrates. Gonadotropin-releasing hormone (GnRH) is the primary stimulatory factor responsible for the hypothalamic control of gonadotropin secretion. In 2000, a previously unidentified hypothalamic neuropeptide was isolated from the brain of Japanese quail and termed gonadotropin-inhibitory hormone (GnIH) based on its ability to directly inhibit gonadotropin release from the cultured quail anterior pituitary gland. One year later, the cDNA sequence that encodes the quail GnIH precursor polypeptide was cloned and was found to encompass two further peptides (GnIH-related peptide (RP)-1 and GnIH-RP-2) besides GnIH. To date, GnIH orthologous have been detected in a variety of vertebrates from fish to humans. These peptides possess a characteristic-LPXRFa (X = L or Q) motif at the C-terminus and are designated as LPXRFa peptides. It is generally accepted that LPXRFa peptides act on GnRH neurons in the hypothalamus to inhibit gonadotropin synthesis and release in addition to affecting the pituitary function in birds and mammals. However, the exact physiological role of LPXRFa is still uncertain in fish and dual actions of LPXRFa on the HPG axis have been observed. Research aiming to elucidate the detailed signaling pathways mediating the actions of LPXRFa on target cells may contribute to understanding the functional divergence of the LPXRFa system in teleosts. Accordingly, this review will discuss the recent advances in LPXRFa receptor signaling, as well as the potential interactions on cell signaling induced by other factors, such as GnRH and kisspeptin.