Effects of metyrapone on hepatic cortisone-cortisol conversion in the rat

In previous studies in human subjects metyrapone has been found to exert si gnificant extra-adrenal effects, consistent with an effect on the Il-reduct ase activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). In the present study the effects of metyrapone on cortisone metabolism by rat live r microsomes were investigated. Aliquots of microsomal preparations were in cubated with NADPH cofactor and different concentrations of cortisone for a range of time intervals up to 30 min. The products of the reaction were ex tracted with ethyl acetate and separated using thin-layer chromatograph. Co rtisol was estimated by radioimmunoassay. There was a linear increase in co rtisol formation over the first 150 sec of the reaction. Over this time per iod metyrapone had no effect on the rate of the reaction. When the reaction was allowed to proceed for 30 min, however, metyrapone caused a 50% decrea se in the amount of cortisol formed. These data suggest that metyrapone may alter cortisone-cortisol conversion by directly interacting with 11 beta-H SD but in this system metyrapone does not appear to have the characteristic s of a conventional enzyme inhibitor.