@article {MENARD997, author = {R. H. MENARD and T. M. GUENTHNER and A. M. TABURET and H. KON and L. R. POHL and J. R. GILLETTE and H. V. GELBOIN and W. F. TRAGER}, title = {Specificity of the In Vitro Destruction of Adrenal and Hepatic Microsomal Steroid Hydroxylases by Thiosteroids}, volume = {16}, number = {3}, pages = {997--1010}, year = {1979}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {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 {\textmu}M), 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 {\textmu}M, 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.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/16/3/997}, eprint = {https://molpharm.aspetjournals.org/content/16/3/997.full.pdf}, journal = {Molecular Pharmacology} }