Abstract
Progesterone metabolism by the rabbit liver microsomal cytochromes P-450 system has been investigated with reverse phase (C18) high performance liquid chromatography. Time-course studies indicated that 6β-OHDOC accumulated as a secondary metabolite produced by the sequential 6β- and 21-hydroxylation of progesterone. When 21-hydroxylation occurred first, DOC accumulated and 6-hydroxylation was reduced. 16-OHP was resistent to secondary metabolism at both the 6- and 21-positions. The variable rates of 21-hydroxylase activity between different rabbits was further influenced by the nature of C-6-function in the order of 6-oxo > 6β -OH > 6α-OH > 6-H > 6β-acetoxy. These results indicate the potential interaction of the microsomal cytochromes P-450 and/or products in the sequential hydroxylation of a single steroid substrate at multiple sites.
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