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  • Title: Depletion of cytochrome P-450 by thyroid hormone and cobalt-protoporphyrin IX in rat liver: evidence that susceptibility varies among forms of the heme protein.
    Author: Rosenberg DW, Drummond GS, Smith TJ.
    Journal: Pharmacology; 1995 Oct; 51(4):254-62. PubMed ID: 8577819.
    Abstract:
    The ability of 3,5,3'-triiodothyronine (T3) and cobalt-protoporphyrin LX (CoPP) to alter the levels of the cytochrome P-450 isoforms, CYP3A2, CYP2E1, CYP2B1 and CYP2B2, was examined in vitro in thyroidectomized adult male rats. With the exception of CYP2B2, CoPP administration resulted in a decline in each of the cytochrome P450 isoforms examined. The effects of T3 administration on immunoreactive levels of cytochrome P-450 were also examined in the liver of thyroidectomized rats. T3 treatment produced a marked depletion in all four cytochrome P-450 isoforms examined. Moreover, this T3-mediated depletion of hepatic cytochrome P-450 occurred in the absence of elevated heme oxygenase levels but in the presence of increased delta-aminolevulinate synthase activity. Thus, CoPP and T3 appear capable of producing isoform-specific downregulation of cytochrome P-450 in the liver of thyroidectomized rats. Based on relative levels of immunoreactive protein, the phenobarbital-inducible isoforms, CYP2B1 and CYP2B2, are most susceptible to T3-mediated suppression. Evidence is presented to suggest that these agents elicit these effects by entirely different mechanisms.
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