In vivo and in vitro studies of the site of inhibitory action of omeprazole on adrenocortical steroidogenesis.
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 beta hydroxyandrosterone, tetrahydrocortisone, tetrahydrocortisol and alpha 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 alpha hydroxycholesterol was inhibited by 83% in the presence of 100 micrograms omeprazole/ml. Conversion from pregnenolone and progesterone and their 17 alpha 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 beta hydroxysteroid dehydrogenase, 17 alpha hydroxylase or 11 beta hydroxylation; 21 hydroxylase activity may be marginally attenuated.
Dowie
L J
LJ
MCR Blood Pressure Unit, Western Infirmary, Glasgow, UK.
Smith
J E
JE
MacGilchrist
A J
AJ
Fraser
R
R
Honour
J W
JW
Reid
J L
JL
Kenyon
C J
CJ
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D000818:Animals; D002417:Cattle; D004311:Double-Blind Method; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis* / Q000378:metabolism / Q000652:urine; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D011897:Random Allocation
D009853:Omeprazole; D006854:Hydrocortisone