The objectives include ascertainment of the qualitative and quantitative alterations in sex hormone production profiles in postmenopausal women and aging men as well as the consequences of these alterations. In postmenopausal women, the dominant aspect of the sex hormone production profile is decreased secretion of estradiol and increased extraglandular formation of estrone. In menopausal women, emphasis will be given to ascertaining the hormonal basis of those events that lead to hot flashes. In aging men, the dominant sex hormone production profile is decreased secretion of testosterone and increased extraglandular formation of estrogen. In both sexes, extraglandular estrogen formation increases with obesity, age, and hepatic disease. The biochemical events that underlie the development of obesity with aging and the role of the adipocyte in the conversion of C19-steroids to estrogens will be examined. The significance of estrogen in the development of androgen-induced prostatic hypertrophy in aging men and the biochemical basis of the potentiating effect of estrogen on androgen-induced prostatic hypertrophy in aging dogs will be studied. The capacity of the hypothalamus to secrete dopamine as a function of aging will be investigated in rats, including the effects of prolactin and serotonin in the stimulation and inhibition, respectively, of dopamine secretion. The role of the cellular internalization of dopamine in the processing of prolactin in lactotrophs will be studied. The subcellular localization in the aging human brain of such bioactive peptides and amines will be examined employing human brain tissue. The subcellular processing of ACTH, including its precursor molecules and metabolites, will be studied.
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