11 beta-hydroxysteroid dehydrogenase and corticosteroid action in Lyon hypertensive rats

Adrenocorticosteroid activity in Lyon hypertensive (LH) and low blood press ure (LL) rat strains differ in several respects. Abnormal activity of 11 be ta-hydroxysteroid dehydrogenase enzymes (11 beta-HSD1 and 11 beta-HSD2), wh ich interconvert corticosterone and inactive 11-dehydrocorticosterone, migh t contribute to the LH phenotype by regulating corticosteroid hormone acces s to receptors. 11 beta-HSD2 (expressed in kidney but not liver) prevents e ndogenous glucocorticoids from binding to mineralocorticoid receptors. 11 b eta-HSD1 (expressed in liver and kidney) favors active glucocorticoid forma tion from 11-dehydrocorticosterone. 11 beta-HSD properties in LH and LL hav e been compared by several approaches: (1) 11 beta HSD activities have been measured in vitro as corticosterone dehydrogenation and in vivo as interco nversion of injected cortisol and cortisone; (2) the effects of cortisol an d cortisone on urine electrolytes and volume have been measured; and (3) 11 beta-HSD mRNA expression has been measured by in situ hybridization. 11 be ta-HSD2 enzyme activities in LH and LL rats were similar and urinary cortis one:cortisol ratios were not different after cortisol injection. Cortisol c aused a natriuresis and kaliuresis in both strains, with a slightly reduced response in LH rats. Renal 11 beta-HSD2 mRNA expression was slightly lower in LH rats. 11 beta-HSD1 was less active in LH than LL rats: enzyme activi ties were lower in tissue extracts; urinary cortisone:cortisol was lower in LL rats after cortisone injections; cortisone increased urine volume in LL but not LH rats; and mRNA levels tended to be lower in LH tissues. We conc lude that 11 beta-HSD1 is impaired in LH rats. The LH phenotype of heavier adrenals, raised corticosterone, and reduced thymus weight is similar to th at described for 11 beta-HSD1 knockout mice.