Document Detail


Estradiol, testosterone, dehydroepiandrosterone and androstenedione: novel derivatives and enantiomers. Interactions with rat liver microsomal cytochrome P450 and antioxidant/radical scavenger activities in vitro.
MedLine Citation:
PMID:  11869824     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Interactions of 27 steroids, among them 17 derivatives such as ethers, sulfates and amidosulfonates derived from 17 beta- and 17 alpha-estradiol, from testosterone and alpha- and beta-dihydrotesosterone and from dehydroepiandrosterone with rat liver microsomal cytochromes P450 (P450) were investigated in vitro by assessing binding to P450 and effects on P450 mediated monooxygenase functions as measured by different model reactions: ethoxyresorufin O-deethylation (EROD), ethoxycoumarin O-deethylation (ECOD) and ethylmorphine N-demethylation (EMND). With the exception of 17 alpha-estradiol-3-dimethylamidosulfonate, estrone, its -3-methylether and -3-amidosulfonate and testosterone, all other steroids displayed type I or reverse type I binding to P450. All steroids inhibited EROD activity in micromolar concentrations. An additional strong inhibition of ECOD and EMND activities was only demonstrated for the androgens and progestins. Estriol, estrone and mestranol displayed less inhibitory actions on the model reactions than estradiol. No major differences in comparison to the parent compounds were noted with the other derivatives. The only exceptions were 17 beta-(8,9-dehydro-14 alpha,15 alpha-methylene)estradiol, which displayed stronger effects than estradiol, and dehydroepiandrosterone-3-sulfate, which was less effective than dehydroepiandrosterone. Possible antioxidant properties of the steroids were examined by the stimulated lipid peroxidation (LPO), H2O2 production, and lucigenin (LC) and luminol (LM) amplified chemiluminescence (CL) using rat liver microsomes. Additionally, the influence on rat whole blood chemiluminescence (WB-CL) was assessed. All the estrogens, but not their methylethers and amidosulfonates inhibited LPO in micromolar concentrations. The effects on the other oxidase model reactions or on WB-CL were less distinct. Only ethinylestradiol and 17 beta-(8,9-dehydro-14 alpha,15 alpha-methylene)estradiol displayed a strong inhibitory action on all model reactions. With the exception of dehydroepiandrosterone-3-sulfate, which in general had only weak effects, the androgen and progestin derivatives, in contrast, strongly decreased H2O2 formation and LM- and LC-CL, but were mostly ineffective on LPO and WB-CL.
Authors:
W Klinger; A Lupp; E Karge; H Baumbach; F Eichhorn; A Feix; F Füldner; S Gernhardt; L Knels; B Kost; G Mertens; F Werner; M Oettel; W Römer; S Schwarz; W Elger; B Schneider
Related Documents :
20619364 - At the crossroads of steroid hormone biosynthesis: the role, substrate specificity and ...
21355544 - Asymmetric carbolithiation of conjugated enynes: a flow microreactor enables the use of...
10978224 - Hemolytic polar steroidal constituents of the starfish aphelasterias japonica.
21351784 - A rapid, one-pot, microwave-influenced synthesis of spiro-2,5-diketopiperazines via a c...
11674534 - (3r)-chiral control of 3-alkyl-3-hydroxy-beta-lactams via addition reaction of imines t...
20091134 - Phenolic compounds from cryptocarya konishii: their cytotoxic and tyrosine kinase inhib...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Toxicology letters     Volume:  128     ISSN:  0378-4274     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2002 Mar 
Date Detail:
Created Date:  2002-02-28     Completed Date:  2002-05-10     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  129-44     Citation Subset:  IM    
Affiliation:
Institute of Pharmacology and Toxicology, Friedrich Schiller University Jena, Nonnenplan 4, D-07743 Jena, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
7-Alkoxycoumarin O-Dealkylase / metabolism
Androstenedione / analogs & derivatives*,  metabolism,  pharmacology
Animals
Chemiluminescent Measurements
Cytochrome P-450 CYP1A1 / metabolism
Cytochrome P-450 Enzyme System / metabolism*
Dehydroepiandrosterone / analogs & derivatives*,  metabolism,  pharmacology
Estradiol / analogs & derivatives*,  metabolism,  pharmacology
Ethylmorphine-N-Demethylase / metabolism
Liver / metabolism
Male
Microsomes, Liver / drug effects*,  enzymology,  metabolism
Rats
Rats, Wistar
Reactive Oxygen Species / metabolism
Testosterone / analogs & derivatives,  metabolism,  pharmacology
Chemical
Reg. No./Substance:
0/Reactive Oxygen Species; 50-28-2/Estradiol; 53-43-0/Dehydroepiandrosterone; 58-22-0/Testosterone; 63-05-8/Androstenedione; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.13.-/7-Alkoxycoumarin O-Dealkylase; EC 1.14.14.1/Cytochrome P-450 CYP1A1; EC 1.5.3.-/Ethylmorphine-N-Demethylase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Extrathyroidal actions of antithyroid thionamides.
Next Document:  Estrogenic isoflavones in rodent diets.