Inactivation of contraceptive steroid hormones by human intestinal clostridia.
Steroid hormones reduced in ring-A are devoid of hormonal activity. In metabolic experiments we found that human fecal flora reduced the delta 4-3-keto structure of natural progestins to 3 alpha-hydroxy, 5 beta-steroid metabolites (3 alpha,5 beta) and of synthetic progestins to a mixture of 3 alpha,5 beta and 3 beta,5 beta compounds. 3 alpha,5 beta-Reductase was synthesized by Clostridium paraputrificum and had a strong affinity for natural progestins such as progesterone. 3 beta,5 beta-Reductase was synthesized by Clostridium innoculin and had a stronger affinity for synthetic progestins. A third enzyme, 3 beta,5 alpha-reductase, was synthesized by St. Luke's strain 209 (Clostridium species "J-1") but was only observed when pure cultures were used. Ring-A reduction of synthetic progestins was 3 to 10 times slower than that of natural progestins, thus explaining the pharmacological superiority of synthetic progestins over naturally occurring analogs.
D003013:Clostridium / Q000378:metabolism*; D003276:Contraceptives, Oral / Q000378:metabolism*; D003278:Contraceptives, Oral, Hormonal / Q000378:metabolism*; D004116:Dimethisterone / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D007422:Intestines / Q000382:microbiology*; D007700:Kinetics; D013058:Mass Spectrometry; D009644:Norgestrel / Q000378:metabolism; D013256:Steroids / Q000378:metabolism
D003276:Contraceptives, Oral; D003278:Contraceptives, Oral, Hormonal; D013256:Steroids; D009644:Norgestrel; D004116:Dimethisterone