ADRENAL ANDROGEN PRODUCTION IN AGING

衰老过程中肾上腺雄激素的产生

• 批准号: 2053562
• 负责人: Charles RICHARD PARKER
• 金额: $ 16.55万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2053562
• 关键词: adrenal glands; adrenocorticotropic hormone; aging; androgens; cortisol; cytochrome P450; dexamethasone; enzyme activity; estradiol; genetic transcription; hormone regulation /control mechanism; hormone therapy; human genetic material tag; human subject; human tissue; hydroxysteroid dehydrogenases; immunocytochemistry; in situ hybridization; messenger RNA; postmortem; steroid hormone biosynthesis; sulfotransferase

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.

人类的衰老与肾上腺的显著不足有关。 脱氢表雄酮和脱氢表雄酮的生产 硫酸盐(DS)。DHA和DS的减少与增加相关 许多衰老后遗症的发生率，如心血管疾病。癌症 胰岛素抵抗。高脂血症和免疫能力受损。这个 DHA和DS肾上腺分泌减少的机制(S)是 未知和衰老对肾上腺分泌其他雄激素的影响 没有明确的定义。目前也不清楚男性的肾上腺功能是否 女性也同样会受到年龄的影响。基于之前的结果 研究肾上腺中的几种酶活性可能会在 衰老：7-羟基酶17，20-裂解酶，3β-羟基类固醇脱氢酶，和 类固醇磺基转移酶。我们建议确定老龄化对以下方面的影响 肾上腺类固醇生物合成途径的上述元件中的每一个 肾上腺对分级剂量ACTH反应的功能测试方法 无论是年轻的还是老年的男性和女性。我们还建议将数量量化 细胞色素P450(17α)、3β-羟基类固醇脱氢酶和 肾上腺标本中类固醇磺基转移酶及其mRNA的表达 对年轻和老年男性和女性的尸检。通过使用建议的 方法，我们希望能够表征由于老化引起的变化 在男性和女性中，以确定变化是否由于 特定肾上腺区域内的酶水平，并确定 这种变化很可能是由于基因转录发生了变化。这个 这些研究的结果应该为进一步研究提供良好的基础。 旨在预防或改善衰老对老年人的影响 人类的肾上腺。