Central nervous system-specific knockout of steroidogenic factor 1 |
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Authors: | Ki Woo Kim Liping Zhao Keith L Parker |
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Institution: | aDepartments of Internal Medicine and Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390-8857, United States |
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Abstract: | Steroidogenic factor 1 (SF-1) is a nuclear receptor that plays important roles in the hypothalamus–pituitary–steroidogenic organ axis. Global knockout studies in mice revealed the essential in vivo roles of SF-1 in the ventromedial hypothalamic (VMH) nucleus, adrenal glands, and gonads. One limitation of global SF-1 knockout mice is their early postnatal death from adrenocortical insufficiency. To overcome limitations of the global knockout mice and to delineate the roles of SF-1 in the brain, we used Cre/loxP recombination technology to genetically ablate SF-1 specifically in the central nervous system (CNS). Mice with CNS-specific knockout of SF-1 mediated by nestin-Cre showed increased anxiety-like behavior, revealing a crucial role of SF-1 in a complex behavioral phenotype. Our studies with CNS-specific SF-1 KO mice also defined roles of SF-1 in regulating the VMH expression of target genes implicated in anxiety and energy homeostasis. Therefore, this review will focus on our recent studies defining the functional roles of SF-1 in the VMH linked to anxiety and energy homeostasis. |
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Keywords: | Arcuate nucleus (ARC) Cannabinoid receptor 1 (CB1R) Central nervous system (CNS) Dorsomedial hypothalamic nucleus (DMH) Knockout (KO) Steroidogenic factor 1 (SF-1) Ventromedial hypothalamic nucleus (VMH) |
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