11-BETA-HYDROXYSTEROID DEHYDROGENASE BIOACTIVITY AND MESSENGER-RNA EXPRESSION IN RAT FOREBRAIN - LOCALIZATION IN HYPOTHALAMUS, HIPPOCAMPUS, AND CORTEX

In peripheral aldosterone target sites (e.g., kidney), 11β-hydroxysteroid dehydrogenase (11β-OHSD) metabolizes corticosterone to inactive 11-dehydrocorticosterone and thus protects mineralocorticoid receptors from exposure to corticosterone in vivo. We have investigated whether 11β-OHSD could account for the site-specific differences in corticosteroid receptor sensitivity to corticosterone in rat brain. Enzyme activity, estimated as the percentage conversion of [3H]corticosterone to [3H] 11-dehydrocorticosterone in the presence of NADP+(200 µM), was: Hippocampus, 55.8 ± 2.7%; cortex, 52 ± 3.1%; pituitary; 40 ± 2%, hypothalamus, 26.1 ± 1.2%; brain stem, 21.4 ± 1.7%; and spinal cord, 12.3 ± 1.8%. Northern blots, using [32P]dCTP-labeled probes from an 11β-OHSD cDNA clone derived from rat liver, showed expression of a single mRNA species in all brain areas, of identical size to 11β-OHSD mRNA in liver and kidney. Highest expression was found in hippocampus and cortex. In situ hybridization, using [35S]UTP-labeled cRNA probes, localized high mRNA expression to cerebral cortex (particularly parietal cortex, layer IV), hippocampus (highest in CA3), hypothalamic medial preoptic area and arcuate nuclei and anterior pituitary. In conclusion, there is localized 11β-OHSD mRNA expression and enzyme bioactivity in rat brain. The distribution of 11β-OHSD corresponds to areas of reduced glucocorticoid or mineralocorticoid receptor affinity for corticosterone. Therefore, 11β-OHSD may regulate the access of corticosterone to cerebral mineralocorticoid and/or glucocorticoid receptors and thus modulate corticosteroid effects on brain function. © 1990 by The Endocrine Society.