In vivo and in vitro studies of the site of inhibitory action of omeprazole on adrenocortical steroidogenesis

Publisher Website
Google Scholar
Abstract
The site of omeprazole inhibition of adrenal steroidogenesis has been sought in vivo by analyzing the patterns of urinary steroid metabolite excretion after 6 days of treatment with placebo/omeprazole. Excretion rates of androsterone, aetiocholanolone, dehydroepiandrosterone, 11 β hydroxyandrosterone, tetrahydrocortisone, tetrahydrocortisol and α cortolone were reduced, indicating a block at an early step in steroidogenesis, possibly cholesterol side-chain cleavage. In vitro studies have confirmed this finding by measuring conversion of added precursors to cortisol in isolated bovine adrenocortical cells. Cortisol synthesis from added 20 α hydroxycholesterol was inhibited by 83% in the presence of 100 µg omeprazole/ml. Conversion from pregnenolone and progesterone and their 17 α hydroxylated derivatives was inhibited by 20–40% whereas cortisol production from added 11 deoxycortisol was not affected. These data suggest that omeprazole primarily inhibits cholesterol cleavage and does not inhibit 3 β hydroxysteroid dehydrogenase, 17 α hydroxylase or 11 β hydroxylation; 21 hydroxylase activity may be marginally attenuated.