PMID- 8969940 OWN - NLM STAT- MEDLINE DCOM- 19970313 LR - 20191024 IS - 0743-5800 (Print) IS - 0743-5800 (Linking) VI - 22 IP - 4 DP - 1996 Nov TI - Adrenal 11 beta-hydroxysteroid dehydrogenase. PG - 771-80 AB - 11 beta-hydroxysteroid dehydrogenase (11 beta-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 (11 beta-HSD1) and a high affinity NAD-dependent dehydrogenase (11 beta-HSD2). We have analysed the expression of 11 beta-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 11 beta-HSD2 mRNA in male versus female intact mouse adrenal. Both 11 beta-HSD isoforms were detected in intact male rat adrenal homogenates. For the 11 beta-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 11 beta-HSD1 mRNA to cells at the corticomedullary junction. 11 beta-HSD2 mRNA was uniformly distributed across the cortex and was low/absent in the medulla. Administration of glycyrrhizic acid in vivo (> 100 mg/kg for 4 days) resulted in inhibition of 11 beta-HSD1 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 11 beta-HSD expression was observed in the rat phaeochromocytoma cell line, PC12 cells, nor in human normal adrenal gland or phaeochromocytoma specimens. There are marked species and sex differences in the expression of 11 beta-HSD isoforms within the adrenal. The role of 11 beta-HSD within the adrenal gland remains obscure, but at least in the rat, the expression of the reductase enzyme, 11 beta-HSD1, to the corticomedullary junction may serve to maintain high medullary glucocorticoid concentrations required for catecholamine biosynthesis. FAU - Shimojo, M AU - Shimojo M AD - Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, England. FAU - Condon, J AU - Condon J FAU - Whorwood, C B AU - Whorwood CB FAU - Stewart, P M AU - Stewart PM LA - eng PT - Journal Article PL - England TA - Endocr Res JT - Endocrine research JID - 8408548 RN - 0 (Isoenzymes) RN - 0 (RNA, Messenger) RN - 0U46U6E8UK (NAD) RN - 53-59-8 (NADP) RN - EC 1.1.- (Hydroxysteroid Dehydrogenases) RN - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases) RN - W980KJ009P (Corticosterone) SB - IM MH - 11-beta-Hydroxysteroid Dehydrogenases MH - Adrenal Gland Neoplasms/enzymology MH - Adrenal Glands/*enzymology MH - Animals MH - Blotting, Northern MH - Corticosterone/metabolism MH - Female MH - Humans MH - Hydroxysteroid Dehydrogenases/genetics/*metabolism MH - In Situ Hybridization MH - Isoenzymes/*metabolism MH - Male MH - Mice MH - Mice, Inbred BALB C MH - NAD/pharmacology MH - NADP/pharmacology MH - Pheochromocytoma/enzymology MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Wistar EDAT- 1996/11/01 00:00 MHDA- 1996/11/01 00:01 CRDT- 1996/11/01 00:00 PHST- 1996/11/01 00:00 [pubmed] PHST- 1996/11/01 00:01 [medline] PHST- 1996/11/01 00:00 [entrez] AID - 10.1080/07435809609043775 [doi] PST - ppublish SO - Endocr Res. 1996 Nov;22(4):771-80. doi: 10.1080/07435809609043775.