Separate and interactive regulation of cytochrome P450 3A4 by triiodothyronine, dexamethasone, and growth hormone in cultured hepatocytes.
Article Details
- CitationCopy to clipboard
Liddle C, Goodwin BJ, George J, Tapner M, Farrell GC
Separate and interactive regulation of cytochrome P450 3A4 by triiodothyronine, dexamethasone, and growth hormone in cultured hepatocytes.
J Clin Endocrinol Metab. 1998 Jul;83(7):2411-6.
- PubMed ID
- 9661620 [ View in PubMed]
- Abstract
CYP3A4, the predominant cytochrome P450 expressed in human liver, is responsible for the metabolism of endogenous steroids and many drugs. On the basis of pharmacokinetic studies in patients with hormonal derangements and the effects of replacement therapy, it has been suggested that iodothyronines decrease CYP3A4-mediated drug metabolism, whereas glucocorticoids and GH enhance CYP3A4 activity. The aim of the present study, using well differentiated human hepatocytes in primary culture, was to examine directly whether hormonal factors regulate CYP3A4 gene expression. Addition of T3 to primary hepatocytes resulted in a marked reduction of CYP3A4-catalyzed testosterone 6 beta-hydroxylase activity and corresponding levels of CYP3A4 protein and messenger ribonucleic acid compared to those in untreated cells. Conversely, both dexamethasone and GH treatment substantially increased CYP3A4 gene expression. None of the hormones studied consistently altered the expression of other human cytochrome P450 genes. We conclude that iodothyronines, glucocorticoids, and GH act directly on human hepatocytes to regulate the expression of CYP3A4, and these effects appear to be exerted at a pretranslational level. Altered regulation of hepatic CYP3A4 is, therefore, likely to account for previous observations concerning the effects of endocrine diseases and hormonal treatments on human cytochrome P450-mediated drug and steroid metabolism.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Octreotide Cytochrome P450 3A4 Protein Humans NoInhibitorDetails Pegvisomant Cytochrome P450 3A4 Protein Humans UnknownInducerDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareCyproterone acetateClobazam The serum concentration of Cyproterone acetate can be decreased when it is combined with Clobazam. DesogestrelClobazam The serum concentration of Desogestrel can be decreased when it is combined with Clobazam. DienogestClobazam The serum concentration of Dienogest can be decreased when it is combined with Clobazam. DiethylstilbestrolClobazam The serum concentration of Diethylstilbestrol can be decreased when it is combined with Clobazam. DrospirenoneClobazam The serum concentration of Drospirenone can be decreased when it is combined with Clobazam.