title: Inhibition by etomidate of steroidogenesis in isolated bovine adrenal cells.
abstract: Adverse side effects of the anaesthetic etomidate have been indirectly linked with inhibition of adrenocorticoid synthesis. The present in vitro study has shown that this is a direct effect and indicated which biosynthetic reactions are affected by etomidate. Isolated bovine adrenocortical cells were incubated with and without 10(-8)M ACTH and with increasing doses of etomidate (0-625 ng/ml). ACTH-stimulated cortisol synthesis was significantly inhibited by a concentration of etomidate (25 ng/ml), which is much less than therapeutic plasma levels (100-500 ng/ml). Both basal and ACTH stimulated synthesis of cortisol, progesterone, 17 alpha hydroxyprogesterone and corticosterone were inhibited by 625 ng etomidate/ml whereas deoxycorticosterone output was more than doubled with this dose of anaesthetic. These observations suggest that etomidate inhibits mitochondrial cytochrome P450-dependent hydroxylation reactions in the adrenal steroidogenic pathway.
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D005045:Etomidate / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques
chemical_list: D000305:Adrenal Cortex Hormones; D007093:Imidazoles; D000324:Adrenocorticotropic Hormone; D005045:Etomidate