am-356 and Body-Weight

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.

Topics: Action Potentials; Animals; Arachidonic Acids; Body Weight; Cell Line; Cells, Cultured; Darkness; Electrophysiology; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; Feeding Behavior; Gene Expression Regulation; Humans; In Vitro Techniques; Mice; Mice, Knockout; Neurons; Phosphorylation; Receptor, Cannabinoid, CB1; Response Elements; Steroidogenic Factor 1; Ventromedial Hypothalamic Nucleus