Abstract

The enzymology and regulation of adrenal cortex steroidogenesis will be studied, with emphasis on the rate-limiting, ACTH- regulated side-chain cleavage of cholesterol. The rate of this mitochondrial reaction is determined by both the enzyme system, cytochrome P-450 side chain cleavage, and the intramitochondrial delivery of cholesterol to the enzyme. The latter appears to utilize a regulated transporter which moves cholesterol from the outer to the inner membrane. Studies include a characterization of the transporter, elucidation of cholesterol pools within the mitochondrion, and modulation of adrenal function by the immune system. Technique include measurement of cytochrome P-450 spin state using uv-visible spectrophotometry; radio-immunoassay; gas chromatography; HPLC; and tissue culture.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK027373-08
Application #
3228255
Study Section
Physical Biochemistry Study Section (PB)
Project Start
1980-08-01
Project End
1992-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
8
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322

  Publications

Stevens, V L; Xu, T; Lambeth, J D (1993) Cholesterol trafficking in steroidogenic cells. Reversible cycloheximide-dependent accumulation of cholesterol in a pre-steroidogenic pool. Eur J Biochem 216:557-63
Stevens, V L; Xu, T; Lambeth, J D (1992) Cholesterol pools in rat adrenal mitochondria: use of cholesterol oxidase to infer a complex pool structure. Endocrinology 130:1557-63
Xu, T S; Bowman, E P; Glass, D B et al. (1991) Stimulation of adrenal mitochondrial cholesterol side-chain cleavage by GTP, steroidogenesis activator polypeptide (SAP), and sterol carrier protein2. GTP and SAP act synergistically. J Biol Chem 266:6801-7
Glass, D B; Robertson, D G; Xu, T S et al. (1991) Chemical synthesis, initial conformational studies, and activity of rat steroidogenesis activator peptide and a truncated analog. Endocr Res 17:307-26
Robertson, D G; Perry, D; Lambeth, J D (1991) Inhibition of mitochondrial cholesterol side-chain cleavage by structural analogs of cholesterol sulfate. Endocr Res 17:297-306
Xu, X S; Xu, T S; Robertson, D G et al. (1989) GTP stimulates pregnenolone generation in isolated rat adrenal mitochondria. J Biol Chem 264:17674-80
Xu, X X; Lambeth, J D (1989) Cholesterol sulfate is a naturally occurring inhibitor of steroidogenesis in isolated rat adrenal mitochondria. J Biol Chem 264:7222-7
Lambeth, J D; Xu, X X (1989) Cholesterol sulfate: a naturally-occurring inhibitor of cholesterol side-chain cleavage which functions at the level of intramitochondrial cholesterol translocation. Endocr Res 15:85-99