European Journal of Clinical Pharmacology

, Volume 35, Issue 6, pp 625–629 | Cite as

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

  • L. J. Dowie
  • J. E. Smith
  • A. J. MacGilchrist
  • R. Fraser
  • J. W. Honour
  • J. L. Reid
  • C. J. Kenyon
Originals

Summary

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.

Key words

omeprazole cortisol synthesis urinary steroid metabolites cholesterol cleavage inhibition adrenal steroidogenesis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Howden CW, Forrest JAH, Reid JL (1984) Effects of single and repeated doses of omeprazole on gastric acid and pepsin secretion in man. Gut 25: 707–710Google Scholar
  2. 2.
    Fellenius E, Berglindh T, Sachs G, Olbe L, Elander B, Sjostrand SE, Wallmark B (1981) Substituted benzimidazoles inhibit gastric (H+ + K+) ATPase. Nature 290: 159–161Google Scholar
  3. 3.
    Sachs G, Berglindh T (1981) Physiology of the parietal cell. In: Johnson LR (ed) Physiology of the alimentary tract. Raven Press, New York, pp 567–602Google Scholar
  4. 4.
    Kenyon CJ, Young Y, Gray CE, Fraser R (1984) Inhibition by etomidate of steroidogenesis in isolated bovine adrenal cells. J Clin Endocrinol Metab 58: 947–949Google Scholar
  5. 5.
    Pont A, Williams PL, Loose DS, Feldman D, Reitz RE, Bochra C, Stevens DA (1982) Ketoconazole blocks adrenal steroid synthesis. Ann Intern Med 97: 370–372Google Scholar
  6. 6.
    Kenyon CJ, Fraser R, Birnie GG, Connell JMC, Lever AF (1986) Dose related in vitro effects of ranitidine and cimetidine on basal and ACTH-stimulated steroidogenesis. Gut 27: 1143–1145Google Scholar
  7. 7.
    Howden CW, Kenyon CJ, Beastall GH, Reid JL (1986) Inhibition by omeprazole of adrenocortical response to ACTH: Clinical studies and experiments on bovine adrenal cortex in vitro. Clin Sci 70: 99–102Google Scholar
  8. 8.
    MacGilchrist AJ, Howden CW, Kenyon CJ, Beastall GH, Reid JL (1987) The effect of omeprazole on endocrine functions in man. Eur J Clin Pharmacol 32: 423–425Google Scholar
  9. 9.
    Lambert A, Frost J, Mitchell R, Wilson AV, Robertson WR (1984) On the site of the anti-adrenal steroidogenic effect of etomidate and megestrol acetate. Clin Endocrinol 21: 721–727Google Scholar
  10. 10.
    Honour JW (1986) Biochemical aspects of congenital adrenal hyperplasia. J Inherited Metab Dis 9 [Suppl 1]: 124–134Google Scholar
  11. 11.
    Kenyon CJ, Fraser R, Connell JMC, Birnie GG, Lever AF (1987) (letter). Gut 28: 1690–1691Google Scholar
  12. 12.
    Howden CW, Meredith PA, Forrest JAH, Reid JL (1984) Oral pharmacokinetics of omeprazole. Eur J Clin Pharmacol 26: 641–643Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • L. J. Dowie
    • 1
  • J. E. Smith
    • 2
  • A. J. MacGilchrist
    • 3
  • R. Fraser
    • 1
  • J. W. Honour
    • 2
  • J. L. Reid
    • 3
  • C. J. Kenyon
    • 1
  1. 1.MCR Blood Pressure UnitWestern InfirmaryGlasgowUK
  2. 2.Chemical Pathology and Cobbold LaboratoriesMiddlesex Hospital Medical SchoolLondonUK
  3. 3.Department of Materia MedicaStobhill General HospitalGlasgowUK

Personalised recommendations