ACTH SENSITIVITY/RESPONSIVITY IN AGING

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 许多衰老后遗症的发生率增加，如心血管疾病 疾病、癌症、胰岛素抵抗、高脂血症和免疫受损 能力。肾上腺分泌减少的机制(S) DHA和DS的变化以及衰老对肾上腺分泌的影响尚不清楚 其他雄激素的定义并不明确。目前也不清楚是否 男性和女性的肾上腺功能随着年龄的增长也会受到类似的影响。 根据以前的研究结果，几种酶活性 肾上腺在衰老过程中可能会发生变化：17-羟基酶，17，20-裂解酶， 3‘-羟基类固醇脱氢酶和类固醇磺基转移酶。我们 建议确定老化对上述每一要素的影响 肾上腺类固醇生物合成途径的功能研究 青年和老年人对分级剂量促肾上腺皮质激素的反应 男人和女人。我们还建议对细胞色素的数量进行量化 P450-176，3‘-羟基类固醇脱氢酶和类固醇磺基转移酶 在尸检中获得的肾上腺标本中它们的mRNA 上了年纪的男人和女人。通过使用拟议的方法，我们预计将 能够描述男性和女性因年龄增长而发生的变化， 确定变化是否由体内酶水平的变化引起 并确定这种变化是否 很可能是由于基因转录改变所致。这些研究的结果 研究应该为进一步的研究提供一个良好的基础 预防或改善衰老对人体肾上腺的影响。

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: 17-hydroxylase, 17, 20-lyase, 3'-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 P450-176, 3'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.