Two peptides that are known to influence appetite, [Neuropeptide Y (NPY) and leptin], have also been found to influence the growth hormone (GH) axis. Neuropeptide Y is an orexigenic factor that can be a potent hypothalamic-simulator of GH secretion. Leptin is known as the appetite suppressing obesity protein that increases in circulation with adiposity. Typically, as fat mass is gained, tonic secretion of GH is suppressed. Alternatively, when weight is lost, tonic secretion of GH is enhanced as is hypothalamic expression of NPY. Recently, it was determined that there are neurons within the ventro-medial hypothalamus in which the mRNA for NPY are co-localized with the mRNA for the leptin receptor. This region of the hypothalamus also synthesizes and secretes GH releasing hormone (GHRH). Thus, it is hypothesized that NPY and leptin act antagonistically to regulate hypothalamic-pituitary secretion of GH, and these responses are dependent on receptor populations for leptin and NPY. This hypothesis will be tested with the following specific aims:
Specific Aim 1 : Determine the associative relationship of serum concentrations of GH to hypothalamic mRNA levels of GHRH, somatostatin, NPY and its receptors, and the receptors for leptin as animals age and adiposity increases.
Specific Aim II : Evaluate antagonistic relationships of NPY and leptin on hypothalamic secretion of GHRH and somatostatin. To make these determinations, effective in vivo models will be utilized in conjunction with the use of radio-immunoassays, ribonuclease protection protection assays, and in situ hybridization. These investigations will provide a better understanding of how metabolic status is interpreted and communicated by the hypothalamus and provide information that may be useful to physicians treating patients suffering from satiety disorders that involve GH.
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