Discussion of the proposal re-emphasized the strong points of the research plan. However, there was some concern that the proposed work may not have a particularly high impact. This factor somewhat moderated enthusiasm DESCRIPTION (adapted from the applicant's abstract): This application proposes experiments to examine how steroid hormone synthesis is controlled in different steroidogenic tissues. To accomplish this, the investigators will focus on the regulation of rat P450c17 in a series of steroidogenic cell lines. These studies will use in vitro transfection and gel shift assays.
In Aim 1, the investigators will identify nuclear proteins from rodent Leydig tumor cell and adrenocortical cell lines that interact with regulatory elements in the rat P450c17 gene.
In Specific Aim 2, they will clone these factors.
In Specific Aim 3, the investigators will explore the role of SF-1 phosphorylation in mediating cAMP and/or basal P450c17 gene expression.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Biochemical Endocrinology Study Section (BCE)
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University of California San Francisco
Obstetrics & Gynecology
Schools of Medicine
San Francisco
United States
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Shi, Yimin; Schonemann, Marcus D; Mellon, Synthia H (2009) Regulation of P450c17 expression in the early embryo depends on GATA factors. Endocrinology 150:946-56
Mellon, Synthia H; Bair, Susanna R; Depoix, Christophe et al. (2007) Translin coactivates steroidogenic factor-1-stimulated transcription. Mol Endocrinol 21:89-105
Brake, Paul B; Bair, Susanna R; Mellon, Synthia H (2005) DNA sequence-dependent regulation of SF-1-mediated transcription. DNA Cell Biol 24:148-60
Hammer, Fabian; Compagnone, Nathalie A; Vigne, Jean-Louis et al. (2004) Transcriptional regulation of P450scc gene expression in the embryonic rodent nervous system. Endocrinology 145:901-12
Mellon, Synthia; Gong, Wenhui; Griffin, Lisa D (2004) Niemann pick type C disease as a model for defects in neurosteroidogenesis. Endocr Res 30:727-35
Bair, Susanna R; Mellon, Synthia H (2004) Deletion of the mouse P450c17 gene causes early embryonic lethality. Mol Cell Biol 24:5383-90
Pandey, Amit V; Mellon, Synthia H; Miller, Walter L (2003) Protein phosphatase 2A and phosphoprotein SET regulate androgen production by P450c17. J Biol Chem 278:2837-44
Mellon, Synthia H; Griffin, Lisa D (2002) Neurosteroids: biochemistry and clinical significance. Trends Endocrinol Metab 13:35-43
Chanoine, J P; Compagnone, N A; Wong, A C et al. (2001) Modulation of steroidogenesis by selenium in a novel adrenal cell line developed using targeted tumorigenesis. Biofactors 14:229-38
Griffin, L D; Conrad, S C; Mellon, S H (2001) Current perspectives on the role of neurosteroids in PMS and depression. Int Rev Neurobiol 46:479-92

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