Steroidogenic factor 1 regulates expression of the cannabinoid receptor 1 in the ventromedial hypothalamic nucleus.
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.
Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas 75390-8857, USA.
Ki Woo
KW
Kim
Young-Hwan
YH
Jo
Liping
L
Zhao
Nancy R
NR
Stallings
Streamson C
SC
Chua
Keith L
KL
Parker
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D003624:Darkness; D004594:Electrophysiology; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics* / Q000378:metabolism; D020218:Response Elements; D054339:Steroidogenic Factor 1 / Q000378:metabolism*; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
D001095:Arachidonic Acids; D043884:Receptor, Cannabinoid, CB1; D054339:Steroidogenic Factor 1; C088155:methanandamide; D048049:Extracellular Signal-Regulated MAP Kinases