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Adrenal 11β-hydroxysteroid dehydrogenase

1996; Taylor & Francis; Volume: 22; Issue: 4 Linguagem: Inglês

10.1080/07435809609043775

1532-4206

Masahito Shimojo, Jennifer C. Condon, Christopher B. Whorwood, Paul M. Stewart,

Hormonal and reproductive studies

11β-hydroxysteroid dehydrogenase (11β-HSD) catalyzes the interconversion of cortisol (F) to inactive cortisone (E) in man (corticosterone (B) to 11-dehydrocorticosterone (A) in rodents) and plays a crucial role in regulating corticosteroid hormone action. Two isoforms of this enzyme have been characterized; a low affinity NADP(H)-dependent enzyme (11β-HSD1) and a high affinity NAD-dependent dehydrogenase (11β-HSD2). We have analysed the expression of 11β-HSD in the rodent and human adrenal gland and have investigated its role with respect to glucocorticoid-mediated catecholamine biosynthesis. Our studies indicated higher expression of 11β-HSD2 mRNA in male versus female intact mouse adrenal. Both 11β-HSD isoforms were detected in intact male rat adrenal homogenates. For the 11β-HSD1 isoform, NADPH-dependent oxo-reductase activity exceeded that of NADP-dependent dehydrogenase activity (188 versus 98 pmol/mg.protein.hr). In situ hybridisation studies indicated specific localisation of 11β-HSD1 mRNA to cells at the corticomedullary junction. 11β-HSD2 mRNA was uniformily distributed across the cortex and was low/absent in the medulla. Administration of glycyrrhizic acid in vivo (>100mg/kg for 4 days) resulted in inhibition of 11β-HSDl mRNA and activity and a decrease in mRNA levels for the glucocorticoid-dependent enzyme, phenylethanolamine N-methyltransferase, whilst levels of the glucocorticoid-independent enzyme, tyrosine hydroxylase were unchanged. No 11β-HSD expression was observed in the rat phaeochromocytoma cell line, PC 12 cells, nor in human normal adrenal gland or phaeochromocytoma specimens. There are marked species and sex differences in the expression of 11β-HSD isoforms within the adrenal. The role of 11β-HSD within the adrenal gland remains obscure, but at least in the rat, the expression of the reductase enzyme, 11β-HSD1, to the corticomedullary junction may serve to maintain high medullary glucocorticoid concentrations required for catecholamine biosynthesis.