EurekaMag.com logo
+ Translate

Specificity of the in vitro destruction of adrenal and hepatic microsomal steroid hydroxylases by thio steroids


, : Specificity of the in vitro destruction of adrenal and hepatic microsomal steroid hydroxylases by thio steroids. Molecular Pharmacology 16(3): 997-1010

Studies are presented to show that thiosteroids such as deacetylspironolactone or 7.alpha.-thiotestosterone may be used as biochemical probes to correlate the amount of cytochrome P-450 associated with specific steriod hydroxylases. The ability of the thiosteroids to destroy cytochrome P-450 differed markedly among microsomes prepared from [rat] liver, [guinea pig] 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 .mu.M), 7.alpha.-thiotestosterone caused a NADPH-dependent destruction of hepatic cytochrome P-450 which was associated with a preferential decrease in the activity of testosterone 7.alpha.-hydroxylase. At 4.5 .mu.M, it caused a NADPH-dependent decrease in 2.beta., 6.beta. and 16.alpha.-testosterone hydroxylase, but no NADPH-dependent decrease in benzo(a)pyrene hydroxylation. The destruction of adrenal cytochrome P-450 by deacetylspironolactone in guinea pig microsomes was concurrent with a decrease in the activity of progesterone 17.alpha.-hydroxylase, but not of progesterone 21-hydroxylase. Studies with radiolabeled deacetylspironolactone suggest that during the loss of cytochrome P-450 by thiosteroids the S 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.

(PDF 0-2 workdays service)

Accession: 006459080

PMID: 119158

Submit PDF Full Text: Here


Submit PDF Full Text

No spam - Every submission is manually reviewed

Due to poor quality, we do not accept files from Researchgate

Submitted PDF Full Texts will always be free for everyone
(We only charge for PDFs that we need to acquire)

Select a PDF file:
Close
Close

Related references

Murray, M.; Zaluzny, L., 1988: Comparative effects of antithrombitic and antimycotic N-substituted imidazoles on rat hepatic microsomal steroid and xenobiotic hydroxylases in vitro. N-Substituted imidazoles have been shown to be potent inhibitors of microsomal mixed-function oxidase activities in vitro and in vivo. In the present study the effects of two antithrombitic (dazmegrel and dazoxiben) and four antimycotic (ketoconaz...

Murray M.; Zaluzny L., 1988: Comparative effects of antithrombotic and antimycotic n substituted imidazoles on rat hepatic microsomal steroid and xenobiotic hydroxylases in vitro. N-Substituted imidazoles have been shown to be potent inhibitors of microsomal mixed-function oxidase activities in vitro and in vivo. In the present study the effects of two antithrombitic (dazmegrel and dazoxiben) and four antimycotic (ketoconaz...

Murray, M.; Zaluzny, L., 1988: Comparative effects of antithrombitic and antimycotic N-substituted imidazoles on rat hepatic microsomal steroid and xenobiotic hydroxylases in vitro. N-Substituted imidazoles have been shown to be potent inhibitors of microsomal mixed-function oxidase activities in vitro and in vivo. In the present study the effects of two antithrombitic (dazmegrel and dazoxiben) and four antimycotic (ketoconaz...

Boettner, B.; Cao, P.; Bernhardt, R., 1998: Changing substrate specificity and product pattern in adrenal cytochrome P-450-dependent steroid hydroxylases. Ishimura, Y [Editor], Shimada, H [Editor], Suematsu, M [Editor] Keio University Symposia for Life Science and Medicine, Vol 1; Oxygen homeostasis and its dynamics 221-230

Murray, M.; Cantrill, E.; Frost, L.; Mehta, I.; Farrell, G.C., 1988: Effects of long-term choline deficiency on hepatic microsomal cytochrome P-450-mediated steroid and xenobiotic hydroxylases in the female rat. Total cytochrome P-450 levels decreased to about 80% of control in hepatic microsomes from female rats maintained for 30 weeks on a choline-deficient diet. Livers from these rats were fibrotic and had extensive fatty infiltration but, unlike liver...

Zhang-Cheng-Ju; Qian-Bei-Li; Gu-Xing-Chu; Ma-Jing, 2008: Establishment of in vitro induction model of rat hepatic microsomal testosterone hydroxylases. AIM To establish all in vitro inductlon model of rat. hepatle microsomal tesLosterone hydroxylase (CYP2A1, CYP2B1/2, CYP2C11 and CYP3A1/2). METHODS Hepatocytes were isolated from adult SD rat.s by the collagenase in situ perfuslon technique. Thre...

Stevens J.C.; Halpert J.R., 1991: Inactivation of adrenal progesterone hydroxylases and testicular 17 20 lyase by 17 beta substituted steroids in vitro. FASEB Journal 5(6): A1517

Sushko, T.A.; Gilep, A.A.; Yantsevich, A.V.; Usanov, S.A., 2013: Role of microsomal steroid hydroxylases in Δ7-steroid biosynthesis. CYP17 (steroid 17α-hydroxylase/17,20-lyase) is a key enzyme in steroid hormone biosynthesis. It catalyzes two independent reactions at the same active center and has a unique ability to differentiate Δ(4)-steroids and Δ(5)-steroids in the 17,20...

Chen R.; Conolly R.B., 1984: In vitro destruction of rat hepatic microsomal cytochrome p 450 by vinylidene chloride. Federation Proceedings 43(3): ABSTRACT 457

Lax, E.R.; Baumann, P.; Schriefers, H., 1984: Changes in the activities of microsomal enzymes involved in hepatic steroid metabolism in the rat after administration of androgenic, estrogenic, progestational, anabolic and catatoxic steroids. Several steroids (5 beta-dihydrotestosterone, 19-nortestosterone, methyltrienolone, norethisterone, medroxyprogesterone acetate, cyproterone acetate, chlormadinone acetate and 16 alpha-cyanopregnenolone) were tested for their ability to influence...