Kisspeptin and GnRH interactions in the reproductive brain of teleosts

Abstract

It is well known that gonadotropin-releasing hormone (Gnrh) has a key role in reproduction by regulating the synthesis and release of gonadotropins from the anterior pituitary gland of all vertebrates. About 25 years ago, another neuropeptide, kisspeptin (Kiss1) was discovered as a metastasis suppressor of melanoma cell lines and then found to be essential for mammalian reproduction as a stimulator of hypothalamic Gnrh and regulator of puberty onset. Soon after, a kisspeptin receptor (kissr) was found in the teleost brain. Nowadays, it is known that in most teleosts the kisspeptin system is composed of two ligands, kiss1 and kiss2, and two receptors, kiss2r and kiss3r. Even though both kisspeptin peptides, Kiss1 and Kiss2, have been demonstrated to stimulate gonadotropin synthesis and secretion in different fish species, their actions appear not to be mediated by Gnrh neurons as in mammalian models. In zebrafish and medaka, at least, hypophysiotropic Gnrh neurons do not express Kiss receptors. Furthermore, kisspeptinergic nerve terminals reach luteinizing hormone cells in some fish species, suggesting a direct pituitary action. Recent studies in zebrafish and medaka with targeted mutations of kiss and/or kissr genes reproduce relatively normally. In zebrafish, single gnrh mutants and additionally those having the triple gnrh3 plus 2 kiss mutations can reproduce reasonably well. In these fish, other neuropeptides known to affect gonadotropin secretion were up regulated, suggesting that they may be involved in compensatory responses to maintain reproductive processes. In this context, the present review explores and presents different possibilities of interactions between Kiss, Gnrh and other neuropeptides known to affect reproduction in teleost fish. Our intention is to stimulate a broad discussion on the relative roles of kisspeptin and Gnrh in the control of teleost reproduction.