Browsing by Subject "Steroidogenic Factor 1"
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Item The Functional Roles of Steroidogenic Factor 1 in the Ventromedial Nucleus of the Hypothalamus(2009-06-17) Kim, Ki Woo; Parker, Keith L.Steroidogenic factor 1 (SF-1) is a nuclear receptor that plays important roles in the hypothalamic-pituitary-steroidogenic organ axis. Global knockout studies in mice revealed the essential in vivo roles of SF-1 in the ventromedial hypothalamic nucleus (VMH), 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, present work will focus on the functional roles of SF-1 in the VMH linked to anxiety and energy homeostasis.Item Multiple Approaches to Study of Steroidogenic Factor 1 : Identification of a Novel Regulatory Element and Identification of Novel Target Genes(2005-05-03) Stallings, Nancy Ruth; Parker, Keith L.Steroidogenic Factor 1 (SF-1) is an essential component of the hypothalamic-pituitary-adrenal-gonadal axis. SF-1 knockout (KO) mice lack adrenals, gonads, the ventromedial hypothalamic nucleus (VMH), and pituitary gonadotropes. SF-1 is a transcription factor implicated in the regulation of many genes important in endocrine function. Research into the regulation of SF-1 expression, mostly focused on the proximal promoter, has been unable to fully explain the expression pattern of SF-1. I used DNase hypersensitivity mapping to search for novel regulatory regions of the SF-1 genomic region. One region between the 6th and 7th exons of SF-1 had tissue specific DNase I hypersensitivity. Analysis of this region revealed high conservation with the human genomic sequence and a smaller region that was also highly conserved in the chicken genomic sequence. Transient transfection assays and electrophoretic mobility shift assays have been employed to investigate this conserved element for enhancer activity. Numerous genes are target genes of SF-1, yet loss of known target genes fail to explain why the adrenals, gonads and VMH fail to develop in SF-1 KO mice. I used an SF-1/eGFP transgene as a reporter in both WT and KO E16.5 embryos. eGFP+ cells from the developing VMH of these mice were collected through the use of FACS. Several potential target genes of SF-1 have been identified and analysis of these genes is an ongoing project.