NEUROENDOCRINE EFFECTS OF INSULIN, IGF-I AND LEPTIN ON THE SECRETION OF THE GONADOTROPIN-RELEASING HORMONE (GnRH)

Abstract

Animal energy balance greatly determines his reproductive success. In the majority of mammals, under a negative energy balance, there is a decrease in the synthesis of the gonadotropin-releasing hormone (GnRH) which reduces the activity of the hypothalamic-pituitary-gonadal axis. When the energy balance is improved, the hypothalamus reacts to this change and reestablishes the secretion of GnRH. Insulin, the insulin growth factor I (IGF-I) and leptin seem to be the main messengers that signal the hypothalamus on the animal energy balance. It has been seen that the peripheral concentrations of these hormones under positive or negative energy states are associated with changes in GnRH secretion. This review shows how IGF-I acts directly on GnRH neurons affecting its synthesis and secretion, whereas that insulin and leptin act on neurons in the arcuate nucleus (ARC), which synapses with GnRH neurons in the medial preoptic zone. Both insulin and leptin decrease the expression of neuropeptide Y (NPY) and therefore the negative effect of NPY on GnRH secretion. On the other hand insulin and leptin stimulating the synthesis of galanin-like peptide (GALP) and proopiomelanocortin (POMC). Both GALP, as well as the POMC metabolites (mainly the melanocyte stimulating hormone) increase the synthesis of GnRH. Finally, leptin increases the expression of kisspeptin in ARC neurons. Kisspeptin has a positive effect on the synthesis and secretion of GnRH.