Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Action Potentials / drug effects
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Animals
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Arachidonic Acids / administration & dosage
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Arachidonic Acids / pharmacology
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Body Weight / drug effects
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Cell Line
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Cells, Cultured
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Darkness
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Electrophysiology
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Enzyme Activation / drug effects
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Feeding Behavior / drug effects
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Gene Expression Regulation* / drug effects
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Humans
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In Vitro Techniques
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Mice
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Mice, Knockout
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Neurons / drug effects
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Neurons / physiology
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Phosphorylation / drug effects
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Receptor, Cannabinoid, CB1 / genetics*
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Receptor, Cannabinoid, CB1 / metabolism
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Response Elements
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Steroidogenic Factor 1 / metabolism*
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Ventromedial Hypothalamic Nucleus / drug effects
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Ventromedial Hypothalamic Nucleus / enzymology
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Ventromedial Hypothalamic Nucleus / metabolism*
Substances
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Arachidonic Acids
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Receptor, Cannabinoid, CB1
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Steroidogenic Factor 1
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methanandamide
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Extracellular Signal-Regulated MAP Kinases