Barbiturates inhibit progesterone synthesis in cultured Leydig tumor cells and 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 was reversible and could be bypassed in the MA-10 cells by using 22-hydroxycholesterol. Human granulosa cell progesterone synthesis was also inhibited in a dose dependent fashion by phenobarbital, secobarbital and barbituric acid. Significant inhibition occurred in dose ranges that would be therapeutic for treating epilepsy. From these data we conclude that barbiturates block steroidogenesis by inhibiting cholesterol transport to the cholesterol side chain cleavage enzyme.
Gocze
P M
PM
Department of Obstetrics and Gynecology, Medical University of Pecs, Hungary.
Szabo
I
I
Porpaczy
Z
Z
Freeman
D A
DA
D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001463:Barbiturates / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology / Q000627:therapeutic use; D007984:Leydig Cell Tumor / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D010634:Phenobarbital / Q000494:pharmacology / Q000627:therapeutic use; D011247:Pregnancy; D011374:Progesterone / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D011863:Radioimmunoassay; D012631:Secobarbital / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D000927:Anticonvulsants; D001463:Barbiturates; D006993:Hypnotics and Sedatives; D012631:Secobarbital; D011374:Progesterone; C032232:barbituric acid; D010634:Phenobarbital