ADRENAL ANDROGEN PRODUCTION IN AGING

人类的衰老与肾上腺皮质激素的显著缺乏有关。 脱氢表雄酮（DHA）和脱氢表雄酮的生产 硫酸盐（DS）。DHA和DS的减少与 许多老年后遗症的发病率，如心血管疾病。癌 胰岛素抵抗高脂血症和免疫能力受损。的 导致肾上腺产生DHA和DS减少的机制是 以及衰老对肾上腺产生其他雄激素的影响 没有明确定义。目前还不清楚男性的肾上腺功能是否 女性也同样受到衰老的影响。根据先前的结果， 研究表明，肾上腺中的几种酶活性可能会在 老化：7-羟化酶17，20-裂解酶，3 β-羟基类固醇脱氢酶，和 类固醇磺基转移酶。 我们建议确定衰老对 肾上腺类固醇生物合成途径的上述元件中的每一个， 肾上腺对不同剂量促肾上腺皮质激素反应的功能测试方法 年轻人和老年人。 我们亦建议量化 细胞色素P450（17 α），3 β-羟基类固醇脱氢酶，和 类固醇磺基转移酶及其mRNA的肾上腺标本， 年轻和老年男女的尸体解剖。 通过使用拟议的 方法，我们希望能够描述由于衰老而引起的变化， 在男性和女性中，以确定变化是否是由于 在特定的肾上腺区的酶水平，并确定是否 这种变化可能是由于基因转录的改变。的 这些研究的结果应该为进一步的研究提供良好的基础 旨在预防或改善衰老对 人体肾上腺

Aging in humans is associated with a striking deficiency in adrenal production of dehydroepiandrosterone (DHA) and dehydroepiandrosterone sulfate (DS). Reductions in DHA and DS have been correlated with increased incidence of many sequelae of aging such as cardiovascular disease. cancer insulin resistance. hyperlipidemia and impaired immune competence. The mechanism(s) responsible for reduced adrenal production of DHA and DS is unknown and the impact of aging on adrenal production of other androgens is not clearly defined. It also is unclear whether adrenal function in men and women is similarly affected with aging. Based on the results of prior studies several enzymatic activities in the adrenal may be altered during aging: 7-hydroxylase 17, 20-lyase, 3beta-hydroxysteroid dehydrogenase, and steroid sulfotransferase. We propose to determine the impact of aging on each of the above elements of the adrenal steroid biosynthetic pathway by means of functional testing of adrenal responses to graded doses of ACTH in young and aged men and women. We also propose to quantify the amount of cytochrome P450(17alpha), 3beta-hydroxysteroid dehydrogenase, and steroid sulfotransferase and their mRNA's in adrenal specimens obtained at autopsy of young and aged men and women. By use of the proposed approaches, we expect to be able to characterize the changes due to aging in men and women, to determine whether changes are due to alterations in enzyme levels within particular adrenal zones, and to establish whether such changes are likely to be due to altered gene transcription. The results of these studies should provide a sound basis for further studies directed toward prevention or amelioration of the effects of aging on the human adrenal.