February 5 2015

12:00 158 Hershey Hall

Stephanie Correa
Cellular and Molecular Pharmacology, University of California, San Francisco

A Neuroendocrine Module Promotes Movement and Normal Body Weight in Females


Estrogen-receptor alpha \(ER\) 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. We have identified a subset of ER+ VMHVL neurons that selectively promotes hormone-dependent female locomotion. Activating Nkx2-1-expressing VMHVL neurons via pharmacogenetics elicits a female-specific burst of spontaneous movement, which requires ER and Tac1 signaling. Disrupting the development of Nkx2-1+ VMHVL neurons results in female-specific obesity, inactivity, and loss of VMHVL neurons co-expressing ER and Tac1. Unexpectedly, two responses controlled by ER+ neurons, fertility and brown adipose tissue thermogenesis, are unaffected. We conclude that a dedicated subset of VMHVL neurons marked by ER, NKX2-1, and Tac1 regulates estrogen-dependent fluctuations in physical activity and constitutes one of several neuroendocrine modules that drive sex-specific responses. Future work in the Correa lab will 1\) molecularly define estrogen-responsive hypothalamic modules, 2\) expand the estrogen-responsive neural circuits that modulate energy homeostasis in females, and 3\) develop neuronal transplantation assays to dissect the physiological consequences of molecularly defined neuronal populations.











































































































































































































































































































































































































































































































































































































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