Direct inhibitory effect of etomidate on corticosteroid secretion in human pathologic adrenocortical cells.
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 of 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(-9)-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 corticosteroid 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 11 beta-hydroxylase enzyme, whereas higher doses of the drug may inhibit earlier steps of the corticosteroid biosynthetic pathway.
Varga
I
I
Second Department of Semmelweis University Medical School, Budapest, Hungary.
Rácz
K
K
Kiss
R
R
Fütö
L
L
Tóth
M
M
Sergev
O
O
Gláz
E
E
D015069:18-Hydroxycorticosterone / Q000378:metabolism; D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000305:Adrenal Cortex Hormones / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000328:Adult; D000450:Aldosterone / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D003900:Desoxycorticosterone / Q000378:metabolism; D005045:Etomidate / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D006929:Hyperaldosteronism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged
D000305:Adrenal Cortex Hormones; D003900:Desoxycorticosterone; D000450:Aldosterone; D015069:18-Hydroxycorticosterone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone; D006854:Hydrocortisone; D005045:Etomidate