Evidence of adrenal 18-hydroxylase inhibition by metyrapone in man.
The influence of metyrapone (M) on the adrenal 18-hydroxylation was studied in two groups of healthy young men. In group I, serum concentrations of 18-OH-11-deoxycorticosterone (18-OH-DOC) fell significantly after a single oral dose of 40 mg/kg of M at 8.00 h, while those of 11-deoxycorticosterone (DOC) increased by a factor of about 500 within 4 hours after drug administration. Serum concentrations of 18-OH-DOC remained suppressed up to 14,00 h and tended to increase up to 16.00 h with a concomitant increase of plasma ACTH. In group II, serum concentrations of 18-OH-DOC and corticosterone (B) were slightly lowered eight hours after oral administration of 30 mg/kg of M at midnight in comparison with measurement of the previous day. Serum concentrations of 11-deoxycortisol (S) and DOC were markedly increased after drug administration. These findings indicate an inhibitory effect of M on adrenal 18-hydroxylation in addition to 11-hydroxylation under in vivo conditions. The slight increase of 18-OH-DOC at 16.00 h in group I and the only slight decrease of this steroid 8 hrs after drug administration in group II may be explained by declining enzyme blockade and a superimposed ACTH stimulation of the adrenal cortex at this time.
D015070:18-Hydroxydesoxycorticosterone / Q000097:blood; D000305:Adrenal Cortex Hormones / Q000097:blood; D000311:Adrenal Glands / Q000187:drug effects / Q000201:enzymology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D003900:Desoxycorticosterone / Q000097:blood; D006801:Humans; D008297:Male; D008797:Metyrapone; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors*
D015070:18-Hydroxydesoxycorticosterone; D000305:Adrenal Cortex Hormones; D003900:Desoxycorticosterone; D000324:Adrenocorticotropic Hormone; D013250:Steroid Hydroxylases; D008797:Metyrapone