An estrogen-responsive module in the ventromedial hypothalamus selectively drives sex-specific activity in females.

Autor:	Correa SM; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA., Newstrom DW; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA., Warne JP; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA., Flandin P; Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USA., Cheung CC; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA., Lin-Moore AT; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA., Pierce AA; Liver Center, University of California, San Francisco, San Francisco, CA 94143, USA., Xu AW; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA., Rubenstein JL; Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: john.rubenstein@ucsf.edu., Ingraham HA; 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. Electronic address: holly.ingraham@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2015 Jan 06; Vol. 10 (1), pp. 62-74. Date of Electronic Publication: 2014 Dec 24.
DOI:	10.1016/j.celrep.2014.12.011
Abstrakt:	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. (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu