Primary and secondary progesterone hydroxylation by the rabbit liver microsomal cytochromes P-450 system.
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 6 beta-OHDOC accumulated as a secondary metabolite produced by the sequential 6 beta- and 21-hydroxylation of progesterone. When 21-hydroxylation occurred first, DOC accumulated and 6-hydroxylation was reduced. 16-OHP was resistant 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 greater than 6 beta-OH greater than 6 beta-OH greater than 6 alpha-OH greater than 6-H greater than 6 beta-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.
Medical School, Memorial University of Newfoundland St John's, Canada.
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D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D005260:Female; D006900:Hydroxylation; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism*; D011817:Rabbits; D013329:Structure-Activity Relationship
D011374:Progesterone; D003577:Cytochrome P-450 Enzyme System