Jeanette Winter

Formation and metabolism of tetrahydrodeoxycorticosterone by human fecal flora

Abstract Incubation of deoxycorticosterone (DOC) with human fecal flora results in the formation of a variety of products depending on the experimental conditions. Fecal flora, diluted 101 to 107, reduced DOC (16 μg/ml) to THDOC which was further metabolized to 3α-pregnanolone. Small amounts of 3α-pregnanolone, in turn, were transformed to pregnandione and 3β-pregnanolone. Another structure, tentatively identified as 20,21-dihydroxy-5-pregnan-3 one (metabolite X) was often formed in yields of 5–10% in the early phases of incubation. These findings were corroborated in experiments using purified THDOC and purified pregnanolone as substrates. Clostridium paraputrificum reduced DOC and progesterone in ring A in yields of 80%. Many nonsporing anaerobes also reduced DOC in ring A but in yields of less than 8%. Some strains of anaerobic organisms transformed DOC to metabolite X which appeared to be an endproduct. Organisms responsible for 21-dehydroxylation have not yet been isolated.

Metabolism of biliary steroids by human fecal flora.

Biliary excreted steroid hormones are metabolized by the intestinal flora. The metabolic pathways of deoxycorticosterone and progesterone, including the bacterial species involved, have been established. The pathways for other biliary steroids are unknown. Information on the biological activities of the metabolites is lacking, but methods for their investigation are now available. Evidence suggests that the formation of the metabolites is influenced by dietary habits, and that, in some cases, it may be controlled by suppression of the responsible bacteria.

Exchange of hydrogen at C-21 during dehydroxylation of deoxycorticosterone by mixed cultures of human fecal flora

Abstract Deoxycorticosterone labeled at C-4 with 14C and at both positions at C-21 with 3H was incubated with mixed cultures of human fecal flora. 3α-Hydroxy-5β-pregnan-20-one, 3β-hydroxy-5β-pregnan-20-one and 5α-pregnane-3,20-dione were isolated and found to contain both isotopes in varying ratios. In every case, more than half of the tritium was lost. These experiments show that the hydrogen at C-21 has a complex role in 21-dehydroxylation by the flora of the gut.