Regulation of Leptin Expression and Function in the Anterior Pituitary

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Leptin is a protein that is normally produced by fat cells to signal the body when there is sufficient fat storage. Leptin signals the brain to regulate food intake, limiting expansion of fat cells. However, sufficient levels of fat cells are important for animal or human reproduction. Thus, the secretion of leptin by fat cells becomes a signal that must rise to critical levels before an animal can go through puberty and reproduce normally. Both leptin and leptin receptors have been found on anterior pituitary cells, which suggest that leptin may also be produced by one cell type to regulate another. This study will focus on this new site for leptin production and regulation. We will test the hypothesis that pituitary gonadotropes can be stimulated to produce leptin by hormones that regulate appetite or reproduction. We will determine if growth hormone cells have leptin receptors and how these receptors are regulated. Since GH breaks down fat cells, these studies may show that that inhibiting GH may be a protective mechanism to allow sufficient fat storage for puberty and onset or maintenance of pregnancy. To that end, we will learn if leptin from gonadotropes inhibits growth hormone (GH) production by pituitary somatotropes. This proposed study uses cell physiology and cell chemistry approaches and experiments to determine how leptin, and its receptors, are regulated in enriched populations of somatotropes and gonadotropes. It will then co-culture these cells to learn if gonadotropes can indeed inhibit somatotropes by their production of leptin. This would be the first demonstration of a pituitary circuit, mediated by leptin, that links hormones that regulate food intake and storage with those that regulate reproductive functions. These studies will provide opportunities for training and development of student and teachers, including underrepresented minorities. Discoveries made under this NSF award will allow the PI to discuss new roles for leptin and provide workshops on obesity and proper nutrition for K-12 teachers and their students.