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.
D000818:Animals; D002393:Estrogens, Catechol / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010882:Piperonyl Butoxide / Q000494:pharmacology; D011166:Porphyrins / Q000494:pharmacology*; D011335:Proadifen / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D002393:Estrogens, Catechol; D011166:Porphyrins; D011524:Protoporphyrins; C007095:cobaltiprotoporphyrin; D011335:Proadifen; D010882:Piperonyl Butoxide