title: Evaluation of 11beta-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 5mg of [1,2,4,19-13C(4),11alpha-2H]cortisol (cortisol-13C(4),2H(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-13C(4),2H(1), cortisone-13C(4), and cortisol-13C(4) together with endogenous cortisol and cortisone. The loss of 11alpha-2H during the conversion of cortisol-13C(4),2H(1) to cortisone-13C(4) by 11beta-HSD2 and the regenerated cortisol-13C(4) from cortisone-13C(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-13C(4),2H(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 13C-label and the 2H-labeling in the 11alpha-position, cortisol-13C(4),2H(1) used in this study served as an appropriate tracer for elucidating the kinetics of the interconversion of cortisol to cortisone in man.
authors.affiliation: Department of Medicinal Chemistry and Clinical Pharmacy, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Japan. kasuyay@ps.toyaku.ac.jp
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Kasuya
authors.forename: Akitomo
authors.initials: A
authors.lastname: Yokokawa
authors.forename: Shinji
authors.initials: S
authors.lastname: Takayama
authors.forename: Hiromi
authors.initials: H
authors.lastname: Shibasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Furuta
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000097:blood*; D000284:Administration, Oral; D000328:Adult; D003348:Cortisone / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D007527:Isoenzymes / Q000097:blood; D007700:Kinetics; D008297:Male
chemical_list: D007527:Isoenzymes; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003348:Cortisone; D006854:Hydrocortisone