PMID- 9302399 OWN - NLM STAT- MEDLINE DCOM- 19971016 LR - 20190813 IS - 0300-0664 (Print) IS - 0300-0664 (Linking) VI - 47 IP - 2 DP - 1997 Aug TI - Additional value of measurement of urinary cortisone and unconjugated cortisol metabolites in assessing the activity of 11 beta-hydroxysteroid dehydrogenase in vivo. PG - 231-6 AB - OBJECTIVE: It has been shown recently that 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) is expressed as at least 2 isozymes. In the liver, 11 beta-HSD1 converts cortisone to cortisol; in the kidney, 11 beta-HSD2 converts cortisol to cortisone. Conventional assessment of 11 beta-HSD activity in vivo has relied on gas chromatographic measurement of the ratios of conjugated cortisol and cortisone metabolites. However, these do not permit distinction between the tissue-specific activities of the enzymes and do not reflect all forms of 11 beta-HSD deficiency. In this report, we have assessed the usefulness of measuring unconjugated cortisol metabolites and free cortisol and cortisone in urine as indices of renal 11 beta-HSD activity in man. DESIGN: Six healthy male subjects established in sodium balance were given either glycyrrhetinic acid (170 mg t.d.s., to inhibit 11 beta-HSD2), carbenoxolone (100 mg t.d.s., to inhibit both 11 beta-HSD1 and 11 beta- HSD2) or both inhibitors in combination. MEASUREMENTS: Urinary electrolytes were measured and the concentrations of total and unconjugated urinary cortisol and its metabolites were determined by gas chromatography mass spectrometry. RESULTS: Glycyrrhetinic acid and carbenoxolone inhibited renal 11 beta-HSD2 to a similar degree, as judged by similar sodium retention. As previously reported, conventional measurement of ratios of total cortisol to cortisone metabolites were influenced to a greater extent by glycyrrhetinic acid (100-200% increase in ratio from baseline) than by carbenoxolone (< 30% increase). However, the effect of carbenoxolone was readily detected by measurement of urinary unconjugated cortisol/cortisone (130-480% increase of ratio from baseline) and also by measurement of ratios of unconjugated cortisol metabolites (60-130% increase). CONCLUSIONS: Measurement of free cortisol and cortisone in urine provides the most sensitive index of renal 11 beta-HSD activity. Measurement of total and conjugated urinary steroids is insensitive in circumstances where 11 beta-HSD activity in liver or elsewhere may be abnormal. FAU - Best, R AU - Best R AD - Department of Medicine, University of Edinburgh, Western General Hospital, UK. FAU - Walker, B R AU - Walker BR LA - eng GR - Wellcome Trust/United Kingdom PT - Clinical Trial PT - Controlled Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Clin Endocrinol (Oxf) JT - Clinical endocrinology JID - 0346653 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Isoenzymes) RN - EC 1.1.- (Hydroxysteroid Dehydrogenases) RN - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases) RN - MM6384NG73 (Carbenoxolone) RN - P540XA09DR (Glycyrrhetinic Acid) RN - V27W9254FZ (Cortisone) RN - WI4X0X7BPJ (Hydrocortisone) SB - IM MH - 11-beta-Hydroxysteroid Dehydrogenases MH - Adult MH - Anti-Inflammatory Agents/*urine MH - Carbenoxolone/pharmacology MH - Cortisone/*urine MH - Gas Chromatography-Mass Spectrometry MH - Glycyrrhetinic Acid/pharmacology MH - Humans MH - Hydrocortisone/*urine MH - Hydroxysteroid Dehydrogenases/antagonists & inhibitors/*metabolism MH - *Isoenzymes MH - Kidney/drug effects/*enzymology MH - Male MH - Sensitivity and Specificity EDAT- 1997/08/01 00:00 MHDA- 1997/09/26 00:01 CRDT- 1997/08/01 00:00 PHST- 1997/08/01 00:00 [pubmed] PHST- 1997/09/26 00:01 [medline] PHST- 1997/08/01 00:00 [entrez] AID - 10.1046/j.1365-2265.1997.2471061.x [doi] PST - ppublish SO - Clin Endocrinol (Oxf). 1997 Aug;47(2):231-6. doi: 10.1046/j.1365-2265.1997.2471061.x.