Regulatory Mechanisms by Appetite-Regulating Peptides of the Neuroendocrine System

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1. Utilizing the push-pull perfusion technique, we investigated the central site at which leptin stimulates the gonadotropin-releasing hormone (GnRH)-luteinizing hormone (LH) system in female rats. We found that leptin acta on both the cell bodies and axon terminals of GnRH neurons to stimulate this neurohormone's release.2. Leptin is also known to stimulate prolactin (PRL) secretion, and we examined its underlying mechanisms. We obtained the data suggesting that α -melanocyte-stimulating hormone (α -MSH) may play a significant role in mediating this hormonal action of leptin, and also that the melanocortin 4 receptor may serve a pivotal role in mediating the α -MSH action.3. We found that nitric oxide in the brain playa a significant role in mediating leptin's facilitatory influences on LH and PRL surges.4. We found that the depressed reproductive function in the obese OLETF female rats is, at least in part, mediated by hyperleptinemia.5. Utilizing the push-pull perfusion method, we examined the mechanism by which leptin stimulates growth hormone (GH) secretion in male rats. We found that growth hormone-releasing factor and somatostatin are important mediators of leptin's actions on GH, but, unexpectedly neurpeptide Y does not seem to play a significant role.6. We examined a possible hormonal action of orexin-A, a potent orexigenic peptide, on reproductive function in female rats. Our results suggest that orexin-A may play a significant role in the generation and maintenance of LH and PRL sures.7. Recent evidence suggests that leukemia inhibitory factor, ciliary neurotrophic factor, and PRL-releasing peptide are also involved in feeding behavior. We found that all three peptides play significant roles in regulating the reproductive system.