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Galbraith RA, Jellinck PH: Cobalt-protoporphyrin causes prolonged inhibition of catechol estrogen synthesis by rat liver microsomes. Biochem Biophys Res Commun. 1987 May 29;145(1):376-83.
A single injection of cobalt-protoporphyrin (CoPP), which produces a marked and sustained decline in hepatic cytochrome P450 content, reduced the ability of male rat liver microsomes to form catechol estrogens to about 30% of control values within 1 day, as measured by the release of 3H2O from [2-3H] estradiol. Two days after treatment, the apparent Km of estrogen 2-hydroxylase for estradiol was increased, but other inhibitors of cytochrome P450 function (SKF-525A or piperonyl butoxide) failed to affect the enzyme. Inhibition by CoPP was also demonstrated by measuring the conversion of [4-14C] estradiol to its 2-hydroxylated derivative visualized by autoradiography after chromatographic separation. These findings point to yet another site in the multifaceted action of cobalt protoporphyrin. |
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