Correa Stephanie M, Newstrom David W, Warne James P, Flandin Pierre, Cheung Clement C, Lin-Moore Alexander T, Pierce Andrew A, Xu Allison W, Rubenstein John L, Ingraham Holly A
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA.
Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Cell Rep. 2015 Jan 6;10(1):62-74. doi: 10.1016/j.celrep.2014.12.011. Epub 2014 Dec 24.
Estrogen-receptor alpha (ERα) neurons in the ventrolateral region of the ventromedial hypothalamus (VMHVL) control an array of sex-specific responses to maximize reproductive success. In females, these VMHVL neurons are believed to coordinate metabolism and reproduction. However, it remains unknown whether specific neuronal populations control distinct components of this physiological repertoire. Here, we identify a subset of ERα VMHVL neurons that promotes hormone-dependent female locomotion. Activating Nkx2-1-expressing VMHVL neurons via pharmacogenetics elicits a female-specific burst of spontaneous movement, which requires ERα and Tac1 signaling. Disrupting the development of Nkx2-1(+) VMHVL neurons results in female-specific obesity, inactivity, and loss of VMHVL neurons coexpressing ERα and Tac1. Unexpectedly, two responses controlled by ERα(+) neurons, fertility and brown adipose tissue thermogenesis, are unaffected. We conclude that a dedicated subset of VMHVL neurons marked by ERα, NKX2-1, and Tac1 regulates estrogen-dependent fluctuations in physical activity and constitutes one of several neuroendocrine modules that drive sex-specific responses.
腹内侧下丘脑腹外侧区域（VMHVL）中的雌激素受体α（ERα）神经元控制一系列性别特异性反应，以实现生殖成功率最大化。在雌性动物中，这些VMHVL神经元被认为协调新陈代谢和生殖。然而，特定神经元群体是否控制这一生理功能的不同组成部分仍不清楚。在这里，我们鉴定出促进激素依赖性雌性运动的ERα VMHVL神经元亚群。通过药物遗传学激活表达Nkx2-1的VMHVL神经元会引发雌性特异性的自发运动爆发，这需要ERα和Tac1信号传导。破坏Nkx2-1(+) VMHVL神经元的发育会导致雌性特异性肥胖、活动减少以及共表达ERα和Tac1的VMHVL神经元丧失。出乎意料的是，由ERα(+)神经元控制的两种反应，即生育能力和棕色脂肪组织产热，并未受到影响。我们得出结论，以ERα、NKX2-1和Tac1为标志的VMHVL神经元特定亚群调节雌激素依赖性的身体活动波动，并构成驱动性别特异性反应的几个神经内分泌模块之一。
