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: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=497169
• 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) 轴是抵御体内平衡威胁（即压力）的前线，它控制着在困难情况下能量储存的调动。 HPA 轴活性的性别差异部分可以通过男性睾酮的抑制作用和女性雌激素的刺激作用来解释。 然而，在大鼠围产期控制雄激素和雌激素暴露会对成年期 HPA 对压力的反应产生深远且永久的（组织）影响。 一些研究继续表明雄激素和雌激素受体参与调节性类固醇对 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，即下丘脑的室旁核，神经元内缺乏直接调节 HPA 流出的性类固醇受体。 因此，性类固醇在大脑中如何以及在何处发挥组织作用尚未得到解决。