Effects of food deprivation and adrenalectomy on CYP3A induction by RU486 in female rats

Cheesman, M. J., Mason, S. R. and Reilly, P. E. B. (1996) Effects of food deprivation and adrenalectomy on CYP3A induction by RU486 in female rats. Journal of Steroid Biochemistry and Molecular Biology, 58 4: 447-454. doi:10.1016/0960-0760(96)00063-5


Author Cheesman, M. J.
Mason, S. R.
Reilly, P. E. B.
Title Effects of food deprivation and adrenalectomy on CYP3A induction by RU486 in female rats
Journal name Journal of Steroid Biochemistry and Molecular Biology   Check publisher's open access policy
ISSN 0960-0760
1879-1220
Publication date 1996-07
Sub-type Article (original research)
DOI 10.1016/0960-0760(96)00063-5
Volume 58
Issue 4
Start page 447
End page 454
Total pages 8
Place of publication Kidlington, Oxford, United Kingdom
Publisher Pergamon
Language eng
Abstract We have studied the effects of food deprivation and adrenalectomy on the induction by RU486 of female rat liver microsomal CYP3A apoprotein, erythromycin N-demethylase and diazepam C3-hydroxylase activities. RU486 was a potent inducer of CYP3A apoprotein in intact animals and food deprivation enhanced this response. Food deprivation alone caused only weak CYP3A apoprotein induction suggesting a synergistic interaction in the regulation of protein expression. These results were reflected in the measurements of diazepam C3-hydroxylase activity. This confirms diazepam C3-hydroxylase as a useful and easily measured index of CYP3A monooxygenase content in female rat liver microsomes. Erythromycin N-demethylase did not show concordance with this pattern; this monooxygenase was much more strongly induced by food deprivation alone than by RU486 administration and, in addition, adrenalectomy abolished the induction response to food deprivation. The lack of correspondence between the apoprotein and erythromycin N-demethylase results suggests that non-CYP3A or novel, hitherto uncharacterized CYP3A isoforms may contribute to erythromycin N-demethylation in female rats. The close agreement between the results for CYP3A apoprotein and diazepam C3-hydroxylase indicates that although RU486 possesses a terminal acetylenic moeity it does not, at the dosages used here, cause mechanism-based inactivation of the CYP3A monooxygenase protein it induces. Current studies are directed to characterizing the particular CYP3A isoform(s) whose production is stimulated by RU486.
Keyword Liver-Microsomes
Hepatic Cytochrome-P-450
Dependent Expression
P450 Activities
8 Isozymes
Purification
Testosterone
Metabolism
Enzymes
Gene
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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Created: Mon, 03 Feb 2014, 13:34:08 EST by Matthew Cheesman on behalf of School of Biomedical Sciences