Participation of a cytochrome P450 enzyme from the 2C subfamily in progesterone 21-hydroxylation in sheep liver.
Progesterone 21-hydroxylation in hepatic microsomes from adult male sheep is a quantitatively important metabolic pathway (0.27 +/- 0.08 nmol deoxycorticosterone formed/min/mg protein; representing 13-25% of total progesterone conversion). This study was undertaken to determine whether the ovine hepatic progesterone 21-hydroxylase may be another member of the P450 2C subfamily, normally associated with progesterone 21-hydroxylation in rodent liver. An IgG preparation raised in rabbits against purified rat liver microsomal cytochrome P450 2C6 was found to recognize a single antigen (MW 52 kDa) in sheep liver microsomes. This protein was present in sheep liver (apparent concentration 16 +/- 4 ng/micrograms microsomal protein) representing approx. 28% of the corresponding content of P450 2C6 in untreated rat liver. Preincubation of the anti-P450 2C6 IgG with hepatic microsomes was found to decrease the rate of progesterone 21-hydroxylation to 50-80% of uninhibited control. Taken together, from these findings it is apparent that a P450 enzyme, most likely from the 2C subfamily, catalyses deoxycorticosterone formation from progesterone in sheep liver and that this is a quantitatively important pathway of progesterone hydroxylation in these fractions.
Murray
M
M
Department of Medicine, University of Sydney, Westmead Hospital, NSW, Australia.
D000818:Animals; D015153:Blotting, Western; D003577:Cytochrome P-450 Enzyme System / Q000276:immunology / Q000302:isolation & purification*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D012756:Sheep; D013255:Steroid 21-Hydroxylase / Q000276:immunology / Q000302:isolation & purification*
D003577:Cytochrome P-450 Enzyme System; D013255:Steroid 21-Hydroxylase