Evaluation of 11β-HSD activities in vivo following oral administration of cortisol-13C4,2H1 to a human subject

This study is concerned with an oral administration of 5 mg of [l,2,4,19-C-13(4),11alpha-H-2]cortisol (cortisol-C-13(4),H-2(1)) to a human subject to reliably evaluate the individual activities of two isozymes of 11beta-HSD. The use of a GC-MS method allowed the simultaneous measurement of the plasma concentrations of cortisol-C-13(4),H-2(1), cortisone-C-13(4), and cortisol-C-13(4) together with endogenous cortisol and cortisone. The loss of 11alpha-H-2 during the conversion of cortisol-C-13(4),H-2(1) to cortisone-C-13(4) by 11beta-HSD2 and the regenerated cortisol-C-13(4) from cortisone-C-13(4) by 11beta-HSD1 provided a direct and accurate means of distinguishing the activities of the two isozymes. The kinetic analysis associated with the metabolism of orally administered cortisol-C-13(4),H-2(1) was of great importance in assessing the 11beta-HSD activities. From a viewpoint of the chemical stability and much less pronounced kinetic isotope effect of the C-13-label and the H-2-labeling in the 11alpha-position, cortisol-C-13(4),H-2(1) used in this study served as an appropriate tracer for elucidating the kinetics of the interconversion of cortisol to cortisone in man. (C) 2002 Elsevier Science Inc. All rights reserved.