METABOLISM OF DEXAMETHASONE - SITES AND ACTIVITY IN MAMMALIAN-TISSUES

We have used in vitro techniques to study the metabolism of dexamethas one. Tissue slices, homogenates and microsomal fractions of various ma mmalian organs from rats and humans have been used. We focused particu larly on the question of whether or not dexamethasone (Dexa) is oxidiz ed at the C-11-OH group by 11beta-hydroxysteroid-dehydrogenase. High a ctivities of this enzyme system for Dexa were localized in renal corte x and rectum. Material from both human and murine liver was ineffectiv e. The main metabolite formed from Dexa in renal and intestinal system s was identified by different mass spectrometric techniques including on line HPLC mass spectrometry as 11-dehydro-dexamethasone. This findi ng was corroborated by the observation that both corticosterone and gl ycyrrhetinic acid block the metabolic transformation of Dexa.