The effect of five synthetic progestational compounds on 5 alpha-reductase activity in genital skin fibroblast monolayers.

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.