Role of gonadotropin-releasing hormone II in the mammalian nervous system

Abstract

Gonadotropin-releasing hormone (GnRH) is a small neuropeptide of which there are multiple structural variants. The first variant identified in mammals, GnRH I, controls the release of pituitary gonadotropins. More recently, a second isoform, GnRH II, first isolated in the bird, was identified in the mammalian brain and periphery. Although it is unlikely to be a primary regulator of gonadotropin release, GnRH II appears to have a wide array of physiological and behavioral functions. GnRH II-containing fibers are present in several nuclei known to regulate reproduction and/or feeding, and its concentration in several of these areas fluctuates in response to changes in food availability, and thus energetic status. In musk shrews, GnRH II acts as a permissive regulator of female reproductive behavior based on energy status, as well as an inhibitor of short-term food intake. In this regard, GnRH II is similar to leptin, neuropeptide Y and several other neurotransmitters that regulate both feeding and reproduction. At least two GnRH receptors are present in the mammalian brain, and increasing evidence suggests that the behavioral effects of GnRH II are mediated by receptor subtypes distinct from the type-1 GnRH receptor (which mediates GnRH I action); the most probable candidate is the type-2 GnRH receptor. GnRH II also regulates the density and/or activity of calcium and potassium channels in the nervous systems of amphibians and fish, a function that may also exist in mammalian neurons. It is likely that the highly conserved GnRH II system has been co-opted over evolutionary time to possess multiple regulatory functions in a broad range of neurobiological aspects.