title: Progesterone hydroxylation and side chain oxidation to acidic metabolites by the pig.
abstract: 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.
authors.affiliation: Medical School, Memorial University of Newfoundland, St John's, Canada.
authors.forename: I R
authors.initials: IR
authors.lastname: Senciall
authors.forename: S
authors.initials: S
authors.lastname: Rahal
mesh_terms: 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
chemical_list: 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