Abstract-Adrenocorticosteroid activity in Lyon hypertensive (LH) and low blood pressure (LL) rat strains differ in several respects. Abnormal activity of 11-hydroxysteroid dehydrogenase enzymes (11-HSD1 and 11-HSD2), which interconvert corticosterone and inactive 11-dehydrocorticosterone, might contribute to the LH phenotype by regulating corticosteroid hormone access to receptors. 11-HSD2 (expressed in kidney but not liver) prevents endogenous glucocorticoids from binding to mineralocorticoid receptors. 11-HSD1 (expressed in liver and kidney) favors active glucocorticoid formation from 11-dehydrocorticosterone. 11-HSD properties in LH and LL have been compared by several approaches: (1) 11HSD activities have been measured in vitro as corticosterone dehydrogenation and in vivo as interconversion of injected cortisol and cortisone; (2) the effects of cortisol and cortisone on urine electrolytes and volume have been measured; and (3) 11-HSD mRNA expression has been measured by in situ hybridization. 11-HSD2 enzyme activities in LH and LL rats were similar and urinary cortisone:cortisol ratios were not different after cortisol injection. Cortisol caused a natriuresis and kaliuresis in both strains, with a slightly reduced response in LH rats. Renal 11-HSD2 mRNA expression was slightly lower in LH rats. 11-HSD1 was less active in LH than LL rats: enzyme activities 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 conclude that 11-HSD1 is impaired in LH rats. The LH phenotype of heavier adrenals, raised corticosterone, and reduced thymus weight is similar to that described for 11-HSD1 knockout mice. (Hypertension. 1999;34:1123-1128.)Key Words: glucocorticoids Ⅲ mineralocorticoids Ⅲ corticosterone Ⅲ cortisol Ⅲ cortisone Ⅲ renal function T he Lyon strains of hypertensive (LH), normotensive (LN), and low blood pressure (LL) rats exhibit different patterns of mineralocorticoid and glucocorticoid hormone secretion depending on age. 1 In young LH rats, concentrations of mineralocorticoids (aldosterone and deoxycorticosterone) are elevated, whereas glucocorticoid levels are low in relation to LL or LN rats. In adulthood, the pattern is reversed. Because both mineralocorticoid and glucocorticoid excess can cause hypertension, 2 it may be that these changing patterns of steroid metabolism could account directly for some of the blood pressure differences between Lyon strains of rat.An important factor in the control of corticosteroid metabolism, particularly in relation to the balance between mineralocorticoid and glucocorticoid hormones, is the enzymatic interconversion of biologically active corticosterone (rodent) and cortisol (humans) to the inactive 11-ketone metabolites, 11-dehydrocorticosterone and cortisone, respectively. 3,4 Two distinct isozymes of 11-hydroxysteroid dehydrogenase (11-HSD1 and 11-HSD2) catalyze this reaction. 11-HSD2 favo...
Glomerular margination of leucocytes occurred early after transplantation and was associated with DSA level and early graft dysfunction. The Banff 07 PTC margination scoring system was easy to apply, especially when CD45 staining was used, and PTC margination grade 3 was always associated with clinical rejection.
11Beta-hydroxysterold dehydrogenase enzymes (11beta-HSD1, 11beta-HSD2) regulate access of adrenocorticosteroids to receptors. 11Beta-HSD2 is a dehydrogenase that protects mineralocorticoid receptors from circulating glucocorticoid hormones, 11beta-HSD1 is a reductase that promotes formation of active hormone in glucocorticoid-sensitive tissues. Here we investigate whether low or high sodium diets affect 11beta-HSD enzyme activities and mRNA expression in liver and kidney tissues. 11Beta-HSD activity was measured as dehydrogenation of 3H-corticosterone by microsomes in the presence of NAD or NADP. In situ hybridisation techniques were used to assess expression of 11beta-HSD1 mRNA (liver and kidney) and 11beta-HSD2 mRNA (kidney). Dietary sodium did not affect 11beta-HSD2 mRNA expression in collecting tubules of the medulla: 11beta-HSD1 mRNA in proximal tubules of the inner cortex/outer medulla was lower after a high sodium diet. 11Beta-HSD1 mRNA in liver was unaffected by treatment. Renal enzyme activity with NAD (11beta-HSD2 cofactor) was lower following a high sodium diet (P < 0.05). In the presence of NADP (11beta-HSD1 co-factor), neither renal nor hepatic activities were affected. Dietary sodium restriction appears to increase 11beta-HSD activity by a non-genomic mechanism; this should enhance aldosterone specificity for mineralocorticoid receptors. 11Beta-HSD1 mRNA expression varies independent of enzyme activity and is not clearly related to altered glucocorticoid activity.
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