3beta-HSD activates DHEA in the songbird brain.
3beta-HSD activates DHEA in the songbird brain.
复制标题
DOI：
--
复制
发表时间：
2008
影响因子：
4.2
通讯作者：
B. Schlinger;D. S. Pradhan;K. Soma
中科院分区：
文献类型：
--
作者：
B. Schlinger;D. S. Pradhan;K. Soma
脱氢表雄酮 (DHEA) 是人体中一种丰富的循环激素原，据报道对中枢和外周组织具有多种作用。尽管 DHEA 含量丰富，但其功能相对未知，因为常见动物模型（实验室大鼠和小鼠）血液中的 DHEA 水平非常低。在过去的十年中，我们从鸟类研究中获得了大量证据，证明 (1) DHEA 是鸣禽体内重要的循环激素原，(2) 3β-羟基类固醇脱氢酶/异构酶 (3β-HSD) 负责将 DHEA 转化为更活跃的雄激素，在鸣禽大脑中高水平表达。在这里，我们首先回顾了生物化学和分子研究，证明了 3β-HSD 在成年和发育中的鸣禽大脑中的广泛活性和表达。检查神经 3beta-HSD 活动的研究表明，性别、压力和季节的影响具有区域特异性。其次，我们回顾了有关圈养和野生鸣禽循环 DHEA 季节性和应激相关变化的研究。第三，我们描述了 DHEA 治疗可以刺激鸣叫行为和控制鸣叫行为的神经回路生长的证据。重要的是，大脑 3β-HSD 和芳香酶可以协同工作，将 DHEA 局部代谢为活性雄激素和雌激素，这对于控制鸣禽的行为和强大的成年神经可塑性至关重要。 DHEA 很可能由禽类性腺和/或肾上腺分泌，就像人类的情况一样，但 DHEA 也可能在鸣禽大脑中从胆固醇或其他前体合成。无论其来源如何，DHEA 似乎是鸣禽体内重要的激素原，而 3β-HSD 是鸣禽大脑中的关键酶。
Dehydroepiandrosterone (DHEA) is an abundant circulating prohormone in humans, with a variety of reported actions on central and peripheral tissues. Despite its abundance, the functions of DHEA are relatively unknown because common animal models (laboratory rats and mice) have very low DHEA levels in the blood. Over the past decade, we have obtained considerable evidence from avian studies demonstrating that (1) DHEA is an important circulating prohormone in songbirds and (2) the enzyme 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD), responsible for converting DHEA into a more active androgen, is expressed at high levels in the songbird brain. Here, we first review biochemical and molecular studies demonstrating the widespread activity and expression of 3beta-HSD in the adult and developing songbird brain. Studies examining neural 3beta-HSD activity show effects of sex, stress, and season that are region-specific. Second, we review studies showing seasonal and stress-related changes in circulating DHEA in captive and wild songbird species. Third, we describe evidence that DHEA treatment can stimulate song behavior and the growth of neural circuits controlling song behavior. Importantly, brain 3beta-HSD and aromatase can work in concert to locally metabolize DHEA into active androgens and estrogens, which are critical for controlling behavior and robust adult neuroplasticity in songbirds. DHEA is likely secreted by the avian gonads and/or adrenals, as is the case in humans, but DHEA may also be synthesized de novo in the songbird brain from cholesterol or other precursors. Irrespective of its source, DHEA seems to be an important prohormone in songbirds, and 3beta-HSD is a key enzyme in the songbird brain.