ACTH SENSITIVITY/RESPONSIVITY IN AGING

衰老过程中 ACTH 的敏感性/反应性

• 批准号: 6244029
• 负责人: Charles RICHARD PARKER
• 金额: $ 2.46万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-02-10 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6244029
• 关键词: adrenal disorder; adrenal glands; adrenocorticotropic hormone; aging; clinical research; corticotropin releasing factor; cytochrome P450; enzyme activity; enzyme mechanism; human subject; hydroxysteroid dehydrogenases; postmortem; steroid biosynthesis; sulfotransferase

Adrenal androgen production is frequently abnormal in women with hyperandrogenic oligo-ovulation (HO). A number of investigators, including ourselves, have noted that AA excess may result from a generalized adrenocortical hyper-reactivity to adrenocorticotropic hormone (ACTH) or pituitary over-response to corticotropin releasing hormone (CRH). This adrenocortical dysfunction may represent an acquired defect secondary to excessive ovarian secretion of androgens, such as testosterone. This proposal aims to establish the sensitivity and responsivity to ACTH and CRH in HO patients with and without adrenocortical dysfunction. To achieve this specific aim the adrenocortical sensitivity and responsivity to incremental doses of ACTH, and to ovine CRH, will be determined in 10 HO patients with and 10 without adrenocrotical hyperreactivity and in 10 control women. The above studies may identify a role for pituitary hyper-responsivity to oCRH, and/or adrenocortical hypersensitivity to ACTH, in HO may suggest that the adrenocortical dysfunction evident in at least 50% of HO patients is primary. Furthermore, it may suggest molecular mechanisms, either in the form of abnormalities of common secondary messengers or ACTH receptor abnormalities. If this were to be the case, further testing would be needed to confirm that this finding is independent of the patient's hormonal milieu. Furthermore, these findings may justify (or discourage) the use of glucocorticoid suppression in these women.

女性的肾上腺雄激素分泌经常异常 高雄激素性寡排卵（HO）。 多名调查人员， 包括我们自己在内，已经注意到 AA 过量可能是由于 全身肾上腺皮质对促肾上腺皮质激素的高反应性 激素（ACTH）或垂体对促肾上腺皮质激素释放的过度反应 激素（CRH）。 这种肾上腺皮质功能障碍可能代表 继发于卵巢雄激素分泌过多的获得性缺陷， 例如睾酮。 该提案旨在建立敏感性 患有或不患有 HO 患者对 ACTH 和 CRH 的反应 肾上腺皮质功能障碍。 为了实现这一具体目标 肾上腺皮质敏感性和对增量剂量的反应 将在 10 名 HO 患者中测定 ACTH 和绵羊 CRH 10 名无肾上腺皮质过度反应性的女性和 10 名对照女性。 这 上述研究可能确定垂体高反应性的作用 oCRH 和/或肾上腺皮质对 ACTH 过敏，在 HO 中可能提示 至少 50% 的 HO 存在明显的肾上腺皮质功能障碍 病人是首要的。 此外，它可能表明分子机制， 以常见第二信使异常的形式或 ACTH 受体异常。 如果是这样的话，进一步 需要进行测试来确认这一发现独立于 患者的荷尔蒙环境。 此外，这些发现可能 证明（或阻止）在这些情况下使用糖皮质激素抑制是合理的 女性。