Oxidoreductive and hydroxylating metabolism of progesterone in rat liver epithelial cell lines.
Mechanisms and sequences of reduction and hydroxylation of progesterone into 6-hydroxypregnanolones were studied in proliferating rat liver epithelial cell cultures. These cell lines had an intense metabolic activity and all the metabolites were unconjugated. The formation of 3 alpha,6 alpha- and 3 beta,6 alpha-dihydroxy-5 alpha-pregnan-20-one was observed when the cells were incubated with progesterone, 5 alpha-pregnane-3,20-dione, 3 alpha- or 3 beta-hydroxy-5 alpha-pregnan-20-one and 6 alpha-hydroxy-5 alpha-pregnane-3,20-dione but not with 6 alpha- or 6 beta-hydroxyprogesterone, 5 beta-pregnane-3,20-dione, 3 alpha- or 3 beta-hydroxy-5 beta-pregnan-20-one. These findings indicate that the potential precursors of the 6 alpha-hydroxypregnanolones have a 5 alpha-configuration. The reduction of 5 alpha-pregnane-3,20-dione at C-3 followed by a 6 alpha-hydroxylation can be postulated as the major, if not the only, metabolic pathway. However, the possibility that 6 alpha-hydroxylation may occur prior to reduction of the C-3 oxo group cannot be entirely ruled out. The stereospecificity of reduction at C-5 and hydroxylation at C-6 are discussed and compared with 6-hydroxylated progesterone metabolites found in man and some other mammals during pregnancy and the neonatal period.
D000375:Aging; D000818:Animals; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D004848:Epithelium / Q000378:metabolism; D005333:Fetus; D006900:Hydroxylation; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D011374:Progesterone / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D011374:Progesterone