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Molecular Endocrinology, doi:10.1210/me.2008-0127
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Molecular Endocrinology 22 (8): 1950-1961
Copyright © 2008 by The Endocrine Society

Steroidogenic Factor 1 Regulates Expression of the Cannabinoid Receptor 1 in the Ventromedial Hypothalamic Nucleus

Ki Woo Kim, Young-Hwan Jo, Liping Zhao, Nancy R. Stallings, Streamson C. Chua, Jr and Keith L. Parker

Departments of Internal Medicine and Pharmacology (K.W.K., L.Z., N.R.S., K.L.P.), UT Southwestern Medical Center, Dallas, Texas 75390-8857; and Division of Endocrinology (Y.-H.J., S.C.C.), Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461

Address all correspondence and requests for reprints to: Keith L. Parker, UT Southwestern/Room Y5.224, 5323 Harry Hines Boulevard, Dallas, Texas 75390-8857. E-mail: keith.parker{at}utsouthwestern.edu.

The nuclear receptor steroidogenic factor 1 (SF-1) plays essential roles in the development and function of the ventromedial hypothalamic nucleus (VMH). Considerable evidence links the VMH and SF-1 with the regulation of energy homeostasis. Here, we demonstrate that SF-1 colocalizes in VMH neurons with the cannabinoid receptor 1 (CB1R) and that a specific CB1R agonist modulates electrical activity of SF-1 neurons in hypothalamic slice preparations. We further show that SF-1 directly regulates CB1R gene expression via a SF-1-responsive element at –101 in its 5'-flanking region. Finally, we show that knockout mice with selective inactivation of SF-1 in the brain have decreased expression of CB1R in the region of the VMH and exhibit a blunted response to systemically administered CB1R agonists. These studies suggest that SF-1 directly regulates the expression of CB1R, which has been implicated in the regulation of energy homeostasis and anxiety-like behavior.

NURSA Molecule Pages Link:

Nuclear Receptors:   SF-1





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