Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD027970-08
Application #
6138768
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
Yoshinaga, Koji
Project Start
1991-08-01
Project End
2001-06-30
Budget Start
2000-01-01
Budget End
2001-06-30
Support Year
8
Fiscal Year
2000
Total Cost
$283,597
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

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
Griffin, L D; Mellon, S H (2001) Biosynthesis of the neurosteroid 3 alpha-hydroxy-4-pregnen-20-one (3 alpha hp), a specific inhibitor of FSH release. Endocrinology 142:4617-22
Zhang, P; Compagnone, N A; Fiore, C et al. (2001) Developmental gonadal expression of the transcription factor SET and its target gene, P450c17 (17alpha-hydroxylase/c17,20 lyase). DNA Cell Biol 20:613-24

Showing the most recent 10 out of 38 publications