The brain processes and integrates metabolic signals from the periphery to regulate body weight and maintain adequate fuel reserves. The activity of the neuroendocrine reproductive axis is gated by metabolic hormones, including leptin and insulin, which reflect metabolic status and whose presence is permissive to reproductive activity. Galanin-like peptide (GALP) is expressed by neurons in the arcuate nucleus that are targets for regulation by leptin and appear to play an important role in the integration of energy homeostasis and reproduction. We have demonstrated that central administration of GALP stimulates GnRH and LH secretion and enhances male sexual behavior. We have also shown that the expression of GALP mRNA in the arcuate nucleus is induced by insulin and suppressed by experimentally induced diabetes. Diabetes is associated with reduced gonadotropin secretion, infertility and dysfunctional sexual behavior. These observations suggest that the impairment of sexual function that accompanies diabetes may be attributable, in part, to reduced activity of GALP neurons in the hypothalamus. Using the laboratory rat as an experimental model, we propose experiments to test this hypothesis and: 1) to explore the molecular pathways by which insulin regulates GALP neurons; 2) to map the sites in the brain where GALP neurons act in the brain to regulate male sexual behavior; and 3) to identify the receptor(s) through which GALP acts to produce its effects on the reproductive axis. We hope this knowledge will lead to a better understanding of the basic biology of GALP's action in the brain, lend insight into the etiology of sexual dysfunction in diabetes, and perhaps provide an enlightened and rational path towards its treatment. ? ?
Showing the most recent 10 out of 110 publications
