Direct inhibitory effect of etomidate on corticosteroid secretion in human pathologic adrenocortical cells

Ibolya Varga, Károly Rácz, Róbert Kiss, László Füt/t:o, Miklós Tóth, Orlin Sergev, Edit Gláz

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Abstract

Etomidate has been shown to inhibit corticosteroid secretion in the normal adrenal gland, but its direct effect in human pathologic adrenals has not been clearly established. In the present study the effect of varying doses of etomidate (10-11 -10-5 M) was investigated on basal and adrenocorticotrophic hormone (ACTH)-stimulated corticosteroid secretions in isolated adrenocortical cells obtained from two patients with primary aldosteronism (adenoma and micronodular hyperplasia) and in those from a patient with Cushing's syndrome (adenoma). In cells from primary aldosteronism, increasing concentrations etomidate (10-11 -10-5 M) produced a dose-dependent decrease of basal and ACTH-stimulated cortisol, aldosterone, 18-hydroxycorticosterone, and corticosterone secretions (ED50: 10-8 M for each of these corticosteroids). In the same cells, the secretions of 11-deoxycortisol and deoxycorticosterone were increased in the presence of low (10-9 - 10-7 M) but not high doses of etomidate (10-6 -10-5 M). In cells from Cushing's syndrome the changes in costicosteroid secretion were similar to those found in primary aldosteronism except that aldosterone and 18-hydroxycorticosterone could not be determined due to their low levels. Thus the potent inhibition of corticosteroids in human pathologic adrenocortical cells in the presence of low concentrations of etomidate may be predominantly due to inhibition of the 11β-hydroxylase enzyme, whereas higher doses of the drug may inhibit earlier steps of the corticosteroid biosynthetic pathway. (Steroids 58:64-68, 1993).

Original languageEnglish
Pages (from-to)64-68
Number of pages5
JournalSteroids
Volume58
Issue number2
DOIs
Publication statusPublished - Feb 1993

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Keywords

  • 11β-hydroxylase enzyme (human)
  • adrenocortical adenoma cells (human)
  • aldosterone inhibitor
  • corticosteroid biosynthesis (human)
  • corticosteroid inhibitor
  • cortisol inhibitor
  • etomidate
  • steroids

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

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