Cobalt-protoporphyrin causes prolonged inhibition of catechol estrogen synthesis by rat liver microsomes

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.