Mechanisms for sex steroid effects on cognition in aging

性类固醇对衰老认知的影响机制

• 批准号: 7065150
• 负责人: JERI JANOWSKY
• 金额: $ 35.76万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7065150
• 关键词: age difference; aging; androgen receptor; aromatase inhibitors; biological signal transduction; clinical research; cognition; estradiol; gender difference; growth hormone releasing hormone; hormone regulation /control mechanism; human old age (65+); human subject; memory; neurology; sex hormones; steroid hormone metabolism; testosterone; young adult human (21-34)

DESCRIPTION (provided by applicant): The last several years have seen an explosion of studies showing relationships between cognitive performance and sex steroid supplementation in men and women. These studies are most notable for their implications for cognitive aging and because they raise the possibility of protection against age-related neurologic diseases or age-related cognitive decline. The mechanism(s) that underlie the cognitive effects of sex steroids in humans are unknown. The overall goal of this research program is to initiate studies of the metabolic pathways that underlie the cognitive effects of sex steroids in human aging. Therefore, we will examine which androgen pathway underlies cognitive effects of androgen supplementation in men (Aim 1) by comparing cognitive performance before and after manipulation of sex steroids. We will administer a gonadotropin releasing hormone agonist, and simultaneously replaced with testosterone (T), T+ an aromatase inhibitor (preventing T's conversion to estradiol (E2)), or a placebo in a double blind manner in both younger and older men. We will examine whether T has cognitive effects in older women and the pathway of these effects by testing cognition in older women before and after T, T+aromatase inhibitor, E2 alone, or no replacement (Aim 2). This research program utilizes a cognitive neuroscience framework such that the critical brain systems for each cognitive domain (working memory, perception, verbal and nonverbal memory, motor sequence learning) have been delineated in previous studies. The tasks are those that particularly decline in aging, and have shown sex differences and/or sex steroid effects in previous studies. Findings that cognitive effects are due to aromatization to E2 in men versus action at T receptors, and findings that T affects cognition in women would give significant direction to the creation of tissue specific, sex steroid-related pharmacologic treatments for brain aging.

描述（由申请人提供）：最近几年的研究爆炸了，表明男性和女性认知表现与补充性类固醇之间的关系。这些研究最引人注目，因为它们对认知衰老的影响，并且因为它们增加了针对与年龄有关的神经系统疾病或与年龄相关的认知能力下降的可能性。性类固醇对人类认知作用的基础的机制尚不清楚。该研究计划的总体目标是开始对性类固醇在人衰老中认知作用的代谢途径的研究。因此，我们将研究哪种雄激素途径是男性补充雄激素补充的认知作用（AIM 1），通过比较操纵性类固醇之前和之后的认知性能。我们将施用促性腺激素释放激素激动剂，并同时用睾丸激素（T），T+ A芳香酶抑制剂（防止T的转化为雌二醇（E2）），或者以年轻男性和年轻男性的双盲方式替代。我们将检查T是否对老年妇女具有认知作用，以及通过测试T，T+芳香酶抑制剂之前和之后的老年妇女的认知，单独使用E2，还是没有替代（AIM 2）。该研究计划采用了认知神经科学框架，以便在先前的研究中划定了每个认知领域的关键大脑系统（工作记忆，感知，言语和非语言记忆，运动序列学习）。任务是那些在衰老中特别下降的任务，并且在先前的研究中显示出性别差异和/或性类固醇的作用。发现认知作用是由于男性与T受体作用的E2的芳香化引起的，并且T会影响女性认知的发现将为创建组织特异性，性类固醇与性类固醇与脑老化的药理治疗提供重要方向。

项目成果

Cognition is not modified by large but temporary changes in sex hormones in men.

男性性激素的大幅但暂时的变化不会改变认知能力。

• DOI: 10.1210/jc.2009-1346
• 发表时间: 2010
• 期刊: The Journal of clinical endocrinology and metabolism
• 作者: Young,LauraA;Neiss,MichelleB;Samuels,MaryH;Roselli,CharlesE;Janowsky,JeriS
• 通讯作者: Janowsky,JeriS

Estrogen, testosterone, and sequential movement in men.

雌激素、睾酮和男性的顺序运动。

• DOI: 10.1037/a0013045
• 发表时间: 2008
• 期刊: Behavioral neuroscience
• 影响因子: 1.9
• 作者: Siegel,JessicaA;Young,LauraA;Neiss,MichelleB;Samuels,MaryH;Roselli,CharlesE;Janowsky,JeriS
• 通讯作者: Janowsky,JeriS