Handa Robert J, Pak Toni R, Kudwa Andrea E, Lund Trent D, Hinds Laura
Department of Biomedical Sciences/Neurosciences Division, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Horm Behav. 2008 May;53(5):741-52. doi: 10.1016/j.yhbeh.2007.09.012. Epub 2007 Dec 11.
The complexity of gonadal steroid hormone actions is reflected in their broad and diverse effects on a host of integrated systems including reproductive physiology, sexual behavior, stress responses, immune function, cognition, and neural protection. Understanding the specific contributions of androgens and estrogens in neurons that mediate these important biological processes is central to the study of neuroendocrinology. Of particular interest in recent years has been the biological role of androgen metabolites. The goal of this review is to highlight recent data delineating the specific brain targets for the dihydrotestosterone metabolite, 5alpha-androstane, 3beta,17beta-diol (3beta-Diol). Studies using both in vitro and in vivo approaches provide compelling evidence that 3beta-Diol is an important modulator of the stress response mediated by the hypothalmo-pituitary-adrenal axis. Furthermore, the actions of 3beta-Diol are mediated by estrogen receptors, and not androgen receptors, often through a canonical estrogen response element in the promoter of a given target gene. These novel findings compel us to re-evaluate the interpretation of past studies and the design of future experiments aimed at elucidating the specific effects of androgen receptor signaling pathways.
性腺甾体激素作用的复杂性体现在它们对一系列整合系统具有广泛而多样的影响，这些系统包括生殖生理学、性行为、应激反应、免疫功能、认知和神经保护。了解雄激素和雌激素在介导这些重要生物学过程的神经元中的具体作用，是神经内分泌学研究的核心。近年来，雄激素代谢产物的生物学作用尤其受到关注。本综述的目的是强调最近的数据，这些数据描绘了二氢睾酮代谢产物5α-雄烷-3β,17β-二醇（3β-二醇）的特定脑靶点。使用体外和体内方法的研究提供了令人信服的证据，表明3β-二醇是下丘脑-垂体-肾上腺轴介导的应激反应的重要调节因子。此外,3β-二醇的作用通常通过给定靶基因启动子中的典型雌激素反应元件，由雌激素受体而非雄激素受体介导。这些新发现促使我们重新评估过去研究的解释以及未来旨在阐明雄激素受体信号通路特定作用的实验设计。
