TESTOSTERONE-MEDIATED REGULATION OF MOUSE RENAL CYTOCHROME-P-450 ISOENZYMES

被引:51
作者
HENDERSON, CJ
SCOTT, AR
YANG, CS
WOLF, CR
机构
[1] IMPERIAL CANC RES FUND,MOLEC PHARMACOL & DRUG METAB LAB,HUGH ROBSON BLDG,GEORGE SQ,EDINBURGH EH8 9XD,SCOTLAND
[2] COLL PHARM,DEPT CHEM BIOL & PHARMACOGNOSY,PISCATAWAY,NJ 08855
关键词
D O I
10.1042/bj2660675
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have studied the extent to which mouse renal cytochrome P-450 isoenzymes are sexually differentiated, and the factor(s) regulating this dimorphism. Intriguingly, sex differences were not seen in the expression of a single cytochrome P-450 enzyme, but were observed in the expression of all P-450 isoenzymes detectable, encoded by six gene families of sub-families. This effect was mediated by testosterone, which had the capacity to both induce and repress P-450 gene expression, and which was independent of growth hormone. The changes in protein content were mirrored in all but one case by changes in the levels of mRNA, indicating that these genes contain hormone-responsive elements. These findings are consistent with numerous reports of sex differences in the susceptibility of the mouse kidney to the toxic and carcinogenic effects of drugs and environmental chemicals, many of which are metabolized to cytotoxic products by the cytochrome P-450-dependent mono-oxygenases. These data imply that circulating androgen levels will be an important factor in susceptibility of the kidney to toxic or carcinogenic compound which require metabolic activation.
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页码:675 / 681
页数:7
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