MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hawke, R. L.
Right arrow Articles by Welch, R. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hawke, R. L.
Right arrow Articles by Welch, R. M.

Major differences in the specificity and regulation of mouse renal cytochrome P-450-dependent monooxygenases. A comparison of xenobiotic and endogenous substrates

RL Hawke and RM Welch

In the present study we have investigated the influence of sex on the specificity of mouse renal microsomes toward endogenous and xenobiotic substrates. Renal microsomes from C3H/HeJ mice were characterized by the following: a 4- to 5-fold male predominance in cytochrome P-450 concentration; a difference between male and female renal microsomes in the absorption maximum for the reduced P-450 . CO complex, 450 and 452 nm, respectively; a lack of a sex difference in lauric acid 12- hydroxylase activity; an 18-fold sex difference (M greater than F) in progesterone 16 alpha-hydroxylase activity; and 8- to 10-fold sex differences (M greater than F) in progesterone 15 alpha-hydroxylase, dimethylnitrosamine demethylase, and lauric acid 11-hydroxylase activities. Treatment of female mice with testosterone propionate selectively induced lauric acid 11-hydroxylase and dimethylnitrosamine demethylase activities 8- and 14-fold, respectively, but had no effect on progesterone 15 alpha- and 16 alpha-hydroxylase activities or on the high female rate of lauric acid 12-hydroxylation. Inhibition studies conducted with male mouse renal microsomes revealed that of the substrates examined, only testosterone inhibited the 15 alpha- and 16 alpha-hydroxylations of progesterone in vitro. In addition, progesterone 15 alpha-hydroxylase was distinguished from 16 alpha- hydroxylase by the greater degree of testosterone inhibition (68 and 44%, respectively) and by sensitivity to metyrapone inhibition. Mouse renal cytochrome P-450 heterogeneity is indicated by the selective effects of androgen induction and metyrapone inhibition. Moreover, distinct modes of regulation are observed between the isozymes involved in steroid hydroxylation and those which catalyze the 11- and 12- hydroxylations of lauric acid in mouse renal microsomes.

Volume 28, Issue 3, pp. 283-289, 09/01/1985
Copyright © 1985 by American Society for Pharmacology and Experimental Therapeutics






Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1985 by the American Society for Pharmacology and Experimental Therapeutics