The role of leptin in nutritional status and reproductive function

Infertility associated with suboptimal nutrition is a major concern among L ivestock producers. Undernourished prepubertal animals will not enter puber ty until they are well fed; similarly, adult, normally cyclic females will stop cycling when faced with extreme undernutrition. Work in our laboratory has focused on how body fat (or adiposity) of an animal can communicate to the brain and regulate reproductive competence. In 1994, the discovery in rodents of the obese (ob) gene product leptin, secreted as a hormone from a dipocytes, provided a unique opportunity to understand and hence regulate w hole body compositional changes, There is now evidence that similar mechani sms are functioning in livestock species in which food intake, body composi tion, and reproductive performance are of considerable economic importance. Leptin has been reported to be a potent regulator of food intake and repro duction in rodents. There is evidence indicating that at least some of the effects of leptin occur through receptor-mediated regulation of the hypotha lamic protein neuropeptide Y (NPY). NPY is a potent stimulator of food inta ke, is present at high concentrations in feed-restricted cattle and ewes, a nd is an inhibitor of LH secretion in these livestock species. In our inves tigations in sheep, we have cloned a partial cDNA corresponding to the ovin e long-form leptin receptor, presumably the only fully active form, and hav e localized the long-form leptin receptor in the ventromedial and arcuate n uclei of the hypothalamus. Leptin receptor mRNA expression was colocalized with NPY mRNA-containing cell bodies in those regions. We have also determi ned that hypothalamic leptin receptor expression is greater in feed-restric ted ewes than in well-fed ewes. These observations provide a foundation for future investigations into the nutritional modulators of reproduction in l ivestock.