Immunochemical and biochemial evidence indicates that an isozyme of cytochrome P-450 in rat liver microsomes catalyzes the formation of a previously unidentified metabolite, 17Beta-hydroxy 4,6-androstadiene-3-one. The identity of the metabolite was confirmed by HPLC, uv spectroscopy and thermospray, mass spectrometry. The metabolite appears to be formed by isozymes of cytochrome P-450 that catalyze the 6Alpha-hydroxylation of testosterone. When animals were treated with various inducers the ratios of 6-hydroxytestosterone over 17Beta-hydroxy 4,6-androstadiene-3-one remained constant. Furthermore, a known 6Beta-hydroxylase inhibitor, 16Alpha-methylprogesterone, inhibited the formation of the metabolite as well as 6Beta-hydroxytestosterone. An antibody raised against a P-450 isozyme isolated from liver microsmes of rats pretreated with dexamethasone also inhibited the formation of both the metabolite and 6Beta-hydroxytestosterone to the same extent.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Intramural Research (Z01)
Project #
1Z01HL000984-01
Application #
3966553
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
U.S. National Heart Lung and Blood Inst
Department
Type
DUNS #
City
State
Country
United States
Zip Code