Abstract:The neuroendocrine regulation of reproduction in vertebrates, including fish, is primarily controlled by the hypothalamo-pituitary-gonadal (HPG) axis, with each component secreting specific neuropeptides or hormones. A classic example of such regulation is the gonadotropin-releasing hormone (GnRH) system. It was believed that GnRH was the only hypothalamic stimulator of the release of pituitary gonadotropins, and that there was no inhibitory neuropeptide in the reproductive axis. However, this notion has been challenged by the recent discovery of a vertebrate hypothalamic neuropeptide that suppresses pituitary gonadotropins release. Gonadotropin-inhibitory hormone (GnIH) is a novel hypothalamic neuropeptide which was identified in 2000 from the brain of Japanese quail (Coturnix japonica). To date, GnIH orthologs have been isolated from fish to mammals and GnIH is the only reported inhibitor of reproduction in any vertebrate. GnIH acts on the pituitary and on GnRH neurons in the hypothalamus to decrease gonadotropin synthesis and release, inhibiting gonadal development and maintenance via a novel G-protein-coupled receptor (GPR147). It is well accepted that GnIH acts as an inhibitory factor in the control of reproduction in birds and mammals. However, the role of GnIH in the control of gonadotropin synthesis and release has been debatable in fish. In this study, we evaluated the effects of GnIH peptides on the reproduction-related gene expression in the hypothalamus of half-smooth tongue sole using a primary hypothalamus culture system for the first time. Our results showed that tsGnIH-1 increased the expression of gnrh2 and gnih mRNAs, but had no effects on gnrh3 or kiss2 mRNA expression. On the other hand, tsGnIH2 significantly inhibited gnrh3 mRNA expression. However, tsGnIH2 altered neither gnrh2, kiss2 nor gnih mRNA levels. Our findings suggested that GnIH peptides derived from the same precursor played different roles in the reproduction-related gene expression in tongue sole, and provided information for the future studies on the regulation of reproduction by GnIH peptides in fish.