The existence of a circulating factor that regulates body weight in mammals has long been postulated. This hormone, now known as leptin, was identified in 1994, and found to be secreted from adipose (fat) tissue. Leptin signals the brain to reduce appetite and increase metabolic rate. Recently, it has become apparent that leptin levels in the blood are elevated during pregnancy in several mammalian species, including human beings. This, and other evidence, has led to the hypothesis that leptin may play previously unrecognized but important roles in the maintenance of pregnancy and the preparation for lactation. The work proposed in this application is designed to investigate this hypothesis, first by determining what tissues secrete leptin during pregnancy, then by determining what factors control its secretion, and ultimately determining what functions leptin performs in the pregnant animal. These goals will be facilitated by the ability to measure small amounts of leptin production from animal tissues in the culture dish. Dr. Widmaier proposes that the placenta becomes a significant source of circulating leptin during pregnancy and that reproductive hormones like estrogen and cortisol stimulate leptin production in placenta. Dr. Widmaier also proposes that the brain becomes less sensitive to leptin during pregnancy, permitting an increased appetite during pregnancy. These questions will be examined in free-ranging bats. A better appreciation of the hormonal correlates of reproduction will not only improve our ability to treat reproductive disorders in people, but will increase our ability to successfully maintain populations of ecologically important animal species. Finally, a better appreciation of the actions of leptin and the control of its secretion will improve our understanding of body weight pathologies in human and animal populations.
