RT Journal Article SR Electronic T1 Specificity of the In Vitro Destruction of Adrenal and Hepatic Microsomal Steroid Hydroxylases by Thiosteroids JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 997 OP 1010 VO 16 IS 3 A1 R. H. MENARD A1 T. M. GUENTHNER A1 A. M. TABURET A1 H. KON A1 L. R. POHL A1 J. R. GILLETTE A1 H. V. GELBOIN A1 W. F. TRAGER YR 1979 UL http://molpharm.aspetjournals.org/content/16/3/997.abstract AB Studies are presented to show that thiosteroids such as deacetylspironolactone or 7α-thiotestosterone may be used as biochemical probes to correlate the amount of cytochrome P-450 associated with specific steroid hydroxylases. The ability of the thiosteroids to destroy cytochrome P-450 differed markedly among microsomes prepared from liver, adrenal and testicular tissues, and seemed proportional to the magnitude of the spectral interactions of the thiosteroids with cytochrome P-450. At low concentrations (1.0 µM), 7α-thiotestosterone caused a NADPH-dependent destruction of hepatic cytochrome P-450 which was associated with a preferential decrease in the activity of testosterone 7α-hydroxylase. At 4.5 µM, it also caused a NADPH-dependent decrease in 2β, 6β, and 16α-testosterone hydroxylase, but no NADPH-dependent decrease in benzo(a)pyrene hydroxylation. The destruction of adrenal cytochrome P-450 by deacetylspironolactone in guinea pig microsornes was concurrent with a decrease in the activity of progesterone 17α-hydroxylase, but not of progesterone 21-hydroxylase. Studies with radiolabeled deacetylspironolactone suggest that during the loss of cytochrome P-450 by thiosteroids the sulfur atom of the thio group after activation by cytochrome P-450 is eliminated from the steroid moiety and binds covalently to the cytochrome P-450-apoenzymes, thereby resulting in the concomitant loss of the activity and the heme of the cytochrome P-450-dependent steroid hydroxylase.