Androgens and Estrogens in the Human Nervous System

人类神经系统中的雄激素和雌激素

• 批准号: RGPIN-2015-03662
• 负责人: Hampson, Elizabeth
• 金额: $ 3.57万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=689771
• 关键词: Androgens; Estrogens; Human; Nervous; System

Reproductive hormones play many important roles in the central nervous system (CNS). During prenatal or early postnatal development, testosterone (or its metabolites) brings about the masculinization and defeminization of brain systems that express receptors for the hormones, permanently altering structural details of brain organization at those sites. Hormones such as estradiol, a form of estrogen, also play important roles in the adult CNS where they serve as potent neuromodulators in several neurochemical systems. The fundamental principles that govern these actions of steroid hormones have been derived mostly from studies of nonhuman species. Much less is known about the roles of these hormones in the brains of humans and other primates. However, evidence increasingly supports a regulatory role for reproductive steroids in a range of cognitive, behavioural, appetitive, and affective functions, as well as hormonal dysregulation in several psychiatric conditions and with brain aging. Research in my lab utilizes a wide range of different methods to investigate the effects of reproductive steroids in the human CNS, including neuropsychological studies of healthy people and people who have endocrine disorders, structural and functional neuroimaging, genotyping, and studies of the CNS correlates of naturally-occurring variations in steroid concentrations. We are assisted in our work by an on-site laboratory that specializes in the quantification of steroid hormones in human saliva using cutting-edge enzyme immunoassays and radioisotopic methods. Over the next 5 years, we plan to study the effects of testosterone and estradiol on several cognitive functions, especially working memory and mental rotation (a type of cognitive processing evoked when we analyze spatial positional information from the external environment). Specifically, we will test the frontal lobe hypothesis, which posits that estradiol acts on the human prefrontal cortex (PFC) and the cognitive functions it serves. Secondly, we will use biological markers of androgen activity and direct quantification of adult hormone concentrations to clarify the timing and mechanisms by which testosterone influences mental rotation and other spatial functions. Collectively, these two lines of research will help to shed new light on the timing and sites of activity of reproductive steroids in the human nervous system.

生殖激素在中枢神经系统（CNS）中发挥着许多重要作用。 在出生前或出生后早期的发育过程中，睾酮（或其代谢产物）会导致表达激素受体的大脑系统男性化和非女性化，永久改变这些部位大脑组织的结构细节。 激素如雌二醇（雌激素的一种形式）在成人中枢神经系统中也起着重要作用，它们在几种神经化学系统中充当有效的神经调质。 支配类固醇激素这些作用的基本原理主要来自对非人类物种的研究。 关于这些激素在人类和其他灵长类动物大脑中的作用，人们所知甚少。 然而，越来越多的证据支持生殖类固醇在一系列认知，行为，食欲和情感功能中的调节作用，以及在几种精神疾病和大脑老化中的激素失调。 在我的实验室研究利用了广泛的不同方法来调查生殖类固醇在人类中枢神经系统的影响，包括健康人和人的神经心理学研究谁有内分泌疾病，结构和功能神经影像学，基因分型，和中枢神经系统的研究相关的类固醇浓度的自然发生的变化。 我们的工作得到了现场实验室的协助，该实验室专门使用最先进的酶免疫测定和放射性同位素方法对人类唾液中的类固醇激素进行定量。 在接下来的5年里，我们计划研究睾酮和雌二醇对几种认知功能的影响，特别是工作记忆和心理旋转（当我们分析来自外部环境的空间位置信息时诱发的一种认知处理）。 具体来说，我们将测试额叶假设，该假设认为雌二醇作用于人类前额叶皮层（PFC）及其所服务的认知功能。 其次，我们将使用雄激素活性的生物标志物和成人激素浓度的直接定量来阐明睾酮影响心理旋转和其他空间功能的时间和机制。 总的来说，这两条研究路线将有助于揭示人类神经系统中生殖类固醇活动的时间和地点。