Document Detail


Interactions of various 19-nor steroids with human placental microsomal cytochrome P-450 (P-450hpm).
MedLine Citation:
PMID:  12875     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Each of seven 19-nor steroids exhibited the capacity to facilitate the binding of carbon monoxide (CO) to human placental microsomal cytochrome P-450 although quantitative differences were shown to exist. In every case the facilitation was antagonized by androstenedione. 19-Norandrostenedione produced the most pronounced effect followed by 19-nortestosterone, nandrolone decanoate, norethandrolone, norgestrel, norethynodrel and norethindrone in that order. All steroids investigated produced typical type I binding spectra when added to placental microsomes. Scatched plots also indicated binding of each steroid to two sites--a high-affinity, low-capacity binding site and a low-affinity, high-capacity binding site. Correlations between affinity for either site and capacity to facilitate binding of CO to the cytochrome were not observed nor were there good correlations between maximal absorbance differences (approximately390-420 nm) producible and facilitation capacity. It was therefore concluded that no definitive relationships existed between facilitation capacity and qualitative or quantitative aspects of the steroid-binding spectra. The capacity to facilitate CO binding appeared to reside in the absence of a chemical group substituted at the 10 position on molecules of androgenic steroids since all investigated steroids possessing 10-methyl or other 10-substituted groups either had no effect on the CO-binding spectrum or caused a displacement of CO from ferrous heme. In contrast, all steroids studied that lacked a substitution at C-10 (19-nor steroids) produced a facilitating effect on heme-ligand binding.
Authors:
M R Juchau; D L Mirkin; P K Zachariah
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Chemico-biological interactions     Volume:  15     ISSN:  0009-2797     ISO Abbreviation:  Chem. Biol. Interact.     Publication Date:  1976 Dec 
Date Detail:
Created Date:  1977-03-21     Completed Date:  1977-03-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0227276     Medline TA:  Chem Biol Interact     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  337-47     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Androstenedione / pharmacology
Binding Sites
Carbon Monoxide / metabolism
Cytochrome P-450 Enzyme System / metabolism*
Female
Humans
Kinetics
Microsomes / drug effects,  metabolism*
NADP / pharmacology
Norsteroids / pharmacology*
Placenta / metabolism*
Pregnancy
Protein Binding
Testosterone / pharmacology
Chemical
Reg. No./Substance:
0/Norsteroids; 53-59-8/NADP; 58-22-0/Testosterone; 63-05-8/Androstenedione; 630-08-0/Carbon Monoxide; 9035-51-2/Cytochrome P-450 Enzyme System

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


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