Abstract

The long-term objective of this project is to understand the various intracellular factors that regulate steroidogenesis. The proposed studies focus on two key enzymes in the production of steroid hormones. The first is the cholesterol side chain cleavage enzyme (P450scc), which carries out the rate-limiting step in the production of steroid hormones. The second enzyme is P450c17, which serves as a key branch point in the production of the different classes of steroid hormones. The proposed studies focus on the transcriptional regulation of the human genes for P450scc and P450c17. The proposed experiments will use human placental JEG-3 cells and human adrenal NCI-H295 cells to study placental- and adrenal-specific expression. Alternative approaches are proposed to clone newly identified transcriptional regulatory proteins, followed by studies to document function in expression studies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK042154-07
Application #
2391424
Study Section
Endocrinology Study Section (END)
Program Officer
Akolkar, Beena
Project Start
1990-01-01
Project End
2000-03-31
Budget Start
1997-04-01
Budget End
1998-03-31
Support Year
7
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

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

  Publications

Miller, Walter L (2002) Androgen biosynthesis from cholesterol to DHEA. Mol Cell Endocrinol 198:7-14
Wang, Xuemei; Zhang, Martin Y H; Miller, Walter L et al. (2002) Novel gene mutations in patients with 1alpha-hydroxylase deficiency that confer partial enzyme activity in vitro. J Clin Endocrinol Metab 87:2424-30
Zhang, Martin Y H; Wang, Xuemei; Wang, Jonathan T et al. (2002) Dietary phosphorus transcriptionally regulates 25-hydroxyvitamin D-1alpha-hydroxylase gene expression in the proximal renal tubule. Endocrinology 143:587-95
Schalkwijk, J; Zweers, M C; Steijlen, P M et al. (2001) A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency. N Engl J Med 345:1167-75
Huang, M C; Miller, W L (2001) Creation and activity of COS-1 cells stably expressing the F2 fusion of the human cholesterol side-chain cleavage enzyme system. Endocrinology 142:2569-76
Song, M; Shao, H; Mujeeb, A et al. (2001) Molten-globule structure and membrane binding of the N-terminal protease-resistant domain (63-193) of the steroidogenic acute regulatory protein (StAR). Biochem J 356:151-8
Lin, C J; Martens, J W; Miller, W L (2001) NF-1C, Sp1, and Sp3 are essential for transcription of the human gene for P450c17 (steroid 17alpha-hydroxylase/17,20 lyase) in human adrenal NCI-H295A cells. Mol Endocrinol 15:1277-93
Miller, W L; Portale, A A (2001) Genetics of vitamin D biosynthesis and its disorders. Best Pract Res Clin Endocrinol Metab 15:95-109
Portale, A A; Miller, W L (2000) Human 25-hydroxyvitamin D-1alpha-hydroxylase: cloning, mutations, and gene expression. Pediatr Nephrol 14:620-5
Martens, J W; Geller, D H; Arlt, W et al. (2000) Enzymatic activities of P450c17 stably expressed in fibroblasts from patients with the polycystic ovary syndrome. J Clin Endocrinol Metab 85:4338-46

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