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

Abstract This study is concerned with an oral administration of 5 mg of [1,2,4,19- 13 C 4 ,11α- 2 H ]cortisol (cortisol- 13 C 4 , 2 H 1 ) to a human subject to reliably evaluate the individual activities of two isozymes of 11β-HSD. The use of a GC–MS method allowed the simultaneous measurement of the plasma concentrations of cortisol- 13 C 4 , 2 H 1 , cortisone- 13 C 4 , and cortisol- 13 C 4 together with endogenous cortisol and cortisone. The loss of 11α- 2 H during the conversion of cortisol- 13 C 4 , 2 H 1 to cortisone- 13 C 4 by 11β-HSD2 and the regenerated cortisol- 13 C 4 from cortisone- 13 C 4 by 11β-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- 13 C 4 , 2 H 1 was of great importance in assessing the 11β-HSD activities. From a viewpoint of the chemical stability and much less pronounced kinetic isotope effect of the 13 C -label and the 2 H -labeling in the 11α-position, cortisol- 13 C 4 , 2 H 1 used in this study served as an appropriate tracer for elucidating the kinetics of the interconversion of cortisol to cortisone in man.