Critical influence of neonatal testosterone on stress pathways in the adult brain

新生儿睾酮对成人大脑应激通路的关键影响

• 批准号: 327441-2009
• 负责人: Viau, Victor
• 金额: $ 1.6万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2009
• 资助国家: 加拿大
• 起止时间: 2009-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=428838
• 关键词: Critical; influence; neonatal; testosterone; stress

A frontline of defense against threats to homeostasis (i.e. stress) is provided by the hypothalamic- pituitary-adrenal (HPA) axis, which governs the mobilization of energy stores under challenging situations. Sex differences in the activity of the HPA axis can be explained, in part, by the inhibitory actions of testosterone in males and by the stimulatory actions of estrogen in females. However, manipulating androgen and estrogen exposure over the perinatal period in the rat causes profound and permanent (organizing) effects on HPA responsiveness to stress during adulthood. Several studies continue to show an involvement of androgen and estrogen receptors in mediating the organizational effects of sex steroids on HPA outflow. However, our research has shown that the principle regulator of the HPA axis, the paraventricular nucleus of the hypothalamus, is devoid of sex steroid receptors within neurons that regulate HPA outflow directly. Thus, how and where the organizing effects of sex steroids are executed in the brain has not been resolved.

下丘脑-垂体-肾上腺（HPA）轴提供了对抗体内平衡威胁（即压力）的防御前线，它控制着挑战性情况下能量储存的动员。 HPA轴活性的性别差异可以部分解释为雄性中睾酮的抑制作用和雌性中雌激素的刺激作用。 然而，操纵雄激素和雌激素暴露在围产期的大鼠在成年期HPA应激反应性的原因深刻和永久（组织）的影响。 一些研究继续表明雄激素和雌激素受体参与介导性类固醇对HPA流出的组织效应。 然而，我们的研究表明，HPA轴的主要调节器，下丘脑室旁核，是缺乏性类固醇受体的神经元内的HPA流出直接调节。 因此，性类固醇的组织效应如何以及在哪里在大脑中执行尚未解决。