Structural diversity of the GnIH/GnIH receptor system in teleost: its involvement in early development and the negative control of LH release.

Gonadotropin inhibitory hormone (GnIH), via binding to GnIH receptor (GnIHR), plays a negative role on the avian and mammalian reproductive axis by inhibiting luteinizing hormone (LH) release. However, the biological significance of the GnIH/GnIHR system in other vertebrates is controversial. To demonstrate the presence of such a system in teleost, we have identified the orthologous gnih genes in zebrafish, stickleback, medaka and Takifugu. Three orthologous genes (gnihr1, gnihr2 and gnihr3) for the gnihr were also identified in zebrafish. The zebrafish gnih precursor contains three putative LPXRFamide peptides. The three zebrafish gnihrs are typical seven transmembrane G protein-coupled receptors sharing high sequence homology with the mammalian and avian GnIHRs (GPR147). Tissue expression studies revealed that zebrafish gnih is mainly expressed in the brain, eye, testis, ovary and spleen, corroborating largely with the tissue expression patterns of the gnihrs in zebrafish. The expression patterns of gnih and its receptors at different developmental stages of zebrafish were also studied. Gnih expression first appeared in the prim-5 stage, and thereafter maintained at a relatively constant level. The three gnihrs could be detected at all embryonic stages of zebrafish and also during early development after hatching. The biological action of the teleost gnih on LH release was further investigated in goldfish in vivo. Intraperitoneal administration of the mature zebrafish gnih peptide (LPXRFa peptide-3) could significantly reduce the basal serum LH level in goldfish. These results provided the first evidence that gnih plays an important role in the negative regulation of LH release in teleost.