Somatopause, the decline of growth hormone (GH) with aging, is due to decreased GH pulse amplitude and might contribute to many of the manifestations of aging. To explain somatopause, one needs to study the regulation of pulsatile GH secretion across the life span. In men but not in women, there is decline of the hypothalamic GH-releasing hormone (GHRH) with aging. The hypothesis of this study is that decreased output of ghrelin, a potent GH secretagogue of gastric origin, contributes to somatopause, and that its role is more prominent in women than in men. The decrease in estrogen levels in menopause might also contribute to somatopause in women and this effect could be mediated through reducing GH secretion. To test the role of ghrelin in somatopause, 12 young women, 12 older menopausal women, 12 young men and 12 older men will be studied. All research participants will be admitted to the General Clinical Research Center for 4 days. After they have blood sampling every 10 min for 24 h to measure ghrelin and GH, they will fast for one day and then blood drawing every 10 min for 24 h will be repeated. Young and older women will be studied twice, during an """"""""estrogen-poor"""""""" period and during an """"""""estrogen-rich"""""""" period that will be created by transdermal estrogen. Young and older men will be studied once. The data will be analyzed to examine the temporal relationships between ghrelin and GH concentrations and to differentiate the effects of age, gender, and estrogen status on ghrelin and GH. The response of ghrelin to fasting will be used as an index of ghrelin reserves. These studies will improve our understanding of the GH changes with aging and will examine the role of ghrelin in GH secretion regulation across the life span. They will also test whether estrogen levels have an effect on ghrelin secretion. GH is widely marketed anti-aging treatment but the available methods of GH administration do not restore normal youthful GH environment. Understanding the mechanisms of somatopause would result in the design new treatments to restore youthful GH secretion in older individuals.
