Barbiturates inhibit progesterone synthesis in cultured Leydig tumor cellsand human granulosa cells

Screening drugs used in obstetrical practice for effects on steroid hormone synthesis revealed that phenobarbital inhibited progesterone synthesis in MA-10 Leydig tumor cells. The inhibition was apparently a drug class effect since it could be reproduced by other barbiturates. Barbiturate blockade w as reversible and could be bypassed in the MA-10 cells by using 22-hydroxyc holesterol. Human granulosa cell progesterone synthesis was also inhibited in a dose dependent fashion by phenobarbital, secobarbital and barbituric a cid. Significant inhibition occurred in dose ranges that would be therapeut ic for treating epilepsy. From these data we conclude that barbiturates blo ck steroidogenesis by inhibiting cholesterol transport to the cholesterol s ide chain cleavage enzyme.