Use of 11α-deuterium labeled cortisol as a tracer for assessing reduced 11β-HSD2 activity in vivo following glycyrrhetinic acid ingestion in a human subject

Abstract This study describes 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 performed on two separate occasions, one with cortisol- 13 C 4 , 2 H 1 alone and the other with cortisol- 13 C 4 , 2 H 1 plus 130 mg per day of glycyrrhetinic acid for 6 days. The stable isotope methodology employed allowed for the evaluation of the individual in vivo activities of the two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD), 11β-HSD1 and 11β-HSD2, and to demonstrate the sensitivity of changes in cortisol elimination half-life for detecting inhibition of 11β-HSD2 activity induced with glycyrrhetinic acid. The kinetic analysis associated with 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 clearly indicated reduced 11β-HSD2 activity with glycyrrhetinic acid ingestion, as observed by an increase in the elimination half-life of cortisol- 13 C 4 , 2 H 1 . The elimination half-life of cortisol- 13 C 4 , 2 H 1 provided sensitive in vivo measures of 11β-HSD2 activity and was more sensitive for detecting changes in renal 11β-HSD2 activity than the measurement of the urinary ratio of free cortisol and free cortisone (UFF/UFE). The 2 H-labeling in the 11α-position of cortisol served as an appropriate tracer for assessing the reduced 11β-HSD2 activity in vivo induced by glycyrrhetinic acid.