Progesterone hydroxylation and side chain oxidation to acidic metabolites by the pig.
The anesthetised pig excreted acidic metabolites of progesterone in the bile and urine. Liver microsomes hydroxylated progesterone at the C-21, 6 beta- and 16 alpha-position and were inhibited by Ketoconazole. The pig exhibited intraspecies variability in progesterone 21- and 6 beta-hydroxylases. Liver, adrenal and to a lesser extent kidney microsomes oxidised the alpha-ketol side-chain to a C-21-oic acid. The liver reaction gave high affinity, low Km kinetics and a Vmax of 28.6 pmol acids mm-1 mg microsomal protein-1. Both carbon monoxide and Ketoconazole were inhibitory. These results implicate the cytochrome P-450 system with the ring and side-chain oxidations of progesterone. The pig resembled the rabbit in its metabolism of progesterone and is the second species in which a microsomal alpha-ketol oxidase has been implicated in the biosynthesis of steroidal acids.
Senciall
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Medical School, Memorial University of Newfoundland, St John's, Canada.
Rahal
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D000311:Adrenal Glands / Q000201:enzymology; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000378:metabolism; D002248:Carbon Monoxide / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D006863:Hydrogen-Ion Concentration; D006900:Hydroxylation; D007654:Ketoconazole / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D011374:Progesterone / Q000378:metabolism* / Q000652:urine; D011817:Rabbits; D013255:Steroid 21-Hydroxylase / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000378:metabolism; D013552:Swine
D011374:Progesterone; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; C022657:steroid hormone 6-beta-hydroxylase; D013255:Steroid 21-Hydroxylase; D000445:Aldehyde Oxidoreductases; C047769:steroid alpha-ketol oxidase; D007654:Ketoconazole