title: The effect of five synthetic progestational compounds on 5 alpha-reductase activity in genital skin fibroblast monolayers.
abstract: The suggestion has been made that prenatal exposure to synthetic progestogens contributes to an increased incidence of hypospadias. One potential mechanism for such an effect might be inhibition of 5 alpha-reductase, a key enzyme in normal male sexual differentiation. We have examined the effect of progesterone and of five synthetic progestogens upon 5 alpha-reductase activity in fibroblast monolayers from 12 genital skin cell lines obtained from normal newborn infants, boys with phimosis and hypospadias and a normal adult male. Basal enzyme activities ranged from 0.8-12.1 pmoles 5 alpha-reduced product/micrograms DNA/hour. Progesterone and norethindrone inhibited 5 alpha-reductase activity in a dose dependent manner to a maximum of 95% and 50% of basal levels respectively at 10(-5) M. Similar concentrations (10(-5) M) of norethynodrel, ethisterone, dl-norgestrel and d-norgestrel had little or no effect. Studies of cell viability showed that the effects of progesterone and norethindrone were specific for 5 alpha-reductase and not non-specific toxic effects.
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D005956:Glucose-6-Phosphate Isomerase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism*; D010413:Penis; D045167:Progesterone Congeners / Q000494:pharmacology*; D012867:Skin / Q000166:cytology / Q000201:enzymology*
chemical_list: D045167:Progesterone Congeners; D004247:DNA; D010088:Oxidoreductases; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D005956:Glucose-6-Phosphate Isomerase