The aims of this project are: 1) to investigate the nature of the steroids in brain and 2) to reinvestigate the biochemical processes by which C-C bonds are cleaved. Of specific concern are those reactions by which C/27-sterols are converted into C/21-steroids (e.g., progesterone) and those by which C/21-steroids are converted into C/19-steroids (e.g., testosterone). The methods required for these studies include radioisotope technology using labeled steroids, in vitro incubations with various tissue preparations, isolation techniques involving various chromatographic procedures (TLC, partition chromatography, HPLC, etc) and spectrometric techniques, such as UV, IR and MS. 1) To study the first objective, we use modern chemical and spectroscopic techniques to characterize the various steroids and steroid conjugates that have reported to be present in brain tissues. Efforts will be made to determine whether pregnenolone or dehydroisoandrosterone are biosynthesized from sterols in brain tissue. When incubated with homogenates of rat brain, pregnenolone is metabolized to more polar compounds. We shall attempt to identify these metabolites since they may provide clues to the functions served by steroids in the brain. 2) We intend to reinvestigate the biochemical processes by which C/21-steroids (pregnenolone, progesterone) are converted into C/19-steroids (dehydroisoandro-sterone, androstenedione, testosterone). It is generally believed that hydroxylation at C-17 (of a C/21-steroid) must precede cleavage of the C-17, C-20 bond. We intend to study the possibility that hydroxylation at C-17 is not an obligatory step in the bioconversion of C/21-steroids to C/19-steroids.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK000110-38
Application #
3224226
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1977-05-01
Project End
1992-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
38
Fiscal Year
1989
Total Cost
Indirect Cost
Name
St. Luke's-Roosevelt Institute for Health Science
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10019
Mathur, C; Prasad, V V; Raju, V S et al. (1993) Steroids and their conjugates in the mammalian brain. Proc Natl Acad Sci U S A 90:85-8