Dehydroxylation of 16 alpha-hydroxyprogesterone by fecal flora of man and rat

Abstract

16 alpha-Hydroxyprogesterone, precursor of biliary 16 alpha-hydroxypregnanolone, was incubated with mixed fecal flora of humans and rats. The major steroid metabolite formed in both systems was 3 alpha-hydroxy-17 alpha-pregnan-20-one. These results demonstrated that the fecal flora reduced the delta 4-3 keto structure, removed the hydroxy group at C-16 and isomerized the side chain from the beta to the alpha configuration. Ring-A reduction of the substrate resulted in a 5 beta-compound with human flora and a 5 alpha-product with rat bacteria. The prevalence of 16 alpha-dehydroxylating organisms varied considerably in human fecal flora and was approximately 10(5)/g of feces in the three rats tested. Rat fecal flora dehydroxylated 16 alpha-hydroxyprogesterone after 4-5 days incubation at 37 degrees C, at pH 6.5-7.5, and with a substrate concentration of 20-80 microgram/ml (optimal condition). Preliminary evidence suggests that 16 alpha-dehydroxylase is exclusively of bacterial origin and is synthesized by an obligate anaerobe.

Keywords

• 16α-dehydroxylation
• 16α-hydroxysteroids
• C17-isomerization
• fecal bacteria
• enterohepatic circ dation
• steroid metabolism