Multiple-sites of inhibition by intravenous metyrapone of human adrenal steroidogenesis

Abstract

Abstract. The in vivo influence of metyrapone on adrenal steroidogenesis has been studied by measuring plasma concentrations of pregnenolone, 17-OH-pregnenolone, progesterone, 17-OH-progesterone, 11-deoxycorticosterone, 11-deoxycortisol, corticosterone, cortisol, 18- OH -11- deoxycorticosterone, 18- OH -corticosterone and aldosterone before, during and after a 5 h infusion of metyrapone ditartrate at doses of 0.2 g/h and 0.8 g/h respectively. Time courses of plasma steroids and corticotrophin indicate an inhibitory effect of metyrapone on total adrenal steroidogenesis in addition to the known inhibition of the 11- and 18-monooxygenase. The effect on total adrenal steroidogenesis is pronounced at high concentrations of metyrapone and may be compensated by corticotrophin. This effect and a concomitant suppressive effect of metyrapone on plasma corticotrophin itself may account for the frequently described falsely abnormal responses to the metyrapone test. From the present 'in vivo' data, no significant, metyrapone induced alterations of the 3β-hydroxysteroid dehydrogenase/Δ5-isomerase, 17-monooxygenase, 21-monooxygenase or the 18-hydroxysteroid dehydrogenase are apparent.