GROWTH HORMONE REGULATING PEPTIDES IN MONKEY HYPOTHALAMUS

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One of the endocrine changes that occurs during reproductive senescence is a reduction in pituitary growth hormone (GH) secretion. This decline in GH is responsible in part for the demise of immune function, muscle mass and energy in many older people. The secretion of GH is regulated primarily by two hypothalamic peptides, i.e., GH-releasing hormone (GHRH) and GH-inhibiting hormone (GHIH, or somatostatin). It is hypothesized that the balance of GHRH and somatostatin activities determines the level of GH in the blood. However, very little is known about how the two peptides are altered during the onset of menopause in females or how and when their imbalance occurs in older males. Our laboratory has developed an in vivo push-pull perfusion technique which allows us to collect and measure the release of hypothalamic peptides in conscious, freely moving monkeys. We initiated a study in which we first established a sensitive radioimmunoassay for both GHRH and somatostatin. As little as 7 pg of GHRH and 2 pg of somatostatin can be detected with these assays. We then prepared the push-pull perfusion device in 8 young male monkeys and measured the endogenous release of GHRH and somatostatin in push-pull perfusates before and after the administration of clonidine, a beta-adrenergic receptor blocker which is known to stimulate GH secretion. Blood samples were also obtained simultaneously with push-pull samples. We found that basal levels of GHRH were readily measurable, whereas basal levels of somatostatin were barely detectible. Interestingly, administration of clonidine initially increased GH levels in the blood without accompanied increase in GHRH. However, during the 2 h following clonidine, both GHRH and GH were elevated. Whether the clonidine-induced initial release of GH is the result of a lowering of somatostatin secretion could not be determined due to its already low secretion in the brain. The results suggest that we have established an in vivo system to monitor the release of GHRH, and periodically somatostain, in young and older monkeys. These assays will allow us to investigate the age-related changes in the brain's regulation of GH secretion.