Effects of metyrapone on hepatic cortisone-cortisol conversion in the rat.
In previous studies in human subjects metyrapone has been found to exert significant extra-adrenal effects, consistent with an effect on the 11-reductase activity of 11beta-hydroxysteroid dehydrogenase (11beta-HSD). In the present study the effects of metyrapone on cortisone metabolism by rat liver microsomes were investigated. Aliquots of microsomal preparations were incubated with NADPH cofactor and different concentrations of cortisone for a range of time intervals up to 30 min. The products of the reaction were extracted with ethyl acetate and separated using thin-layer chromatograph. Cortisol was estimated by radioimmunoassay. There was a linear increase in cortisol formation over the first 150 sec of the reaction. Over this time period 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% decrease in the amount of cortisol formed. These data suggest that metyrapone may alter cortisone-cortisol conversion by directly interacting with 11beta-HSD but in this system metyrapone does not appear to have the characteristics of a conventional enzyme inhibitor.
Thomson
L M
LM
Department of Biochemistry, St Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College.
Raven
P W
PW
Smith
K E
KE
Hinson
J P
JP
D000818:Animals; D002855:Chromatography, Thin Layer; D003348:Cortisone / Q000378:metabolism*; D006854:Hydrocortisone / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008797:Metyrapone / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D003348:Cortisone; D006854:Hydrocortisone; D008797:Metyrapone