1lβ-Hydroxysteroid Dehydrogenase Bioactivity and Messenger RNA Expression in Rat Forebrain: Localization in Hypothalamus, Hippocampus, and Cortex*

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Abstract
In peripheral aldosterone target sites (e.g., kidney), 11.beta.-hydroxysteroid dehydrogenase (11.beta.-OHSD) metabolizes corticosterone to inactive 11-dehydrocorticosterone and thus protects mineralocorticoid receptors from exposure to corticosterone in vivo. We have investigated whether 11.beta.-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 .mu.M), 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 11.beta.-OHSD cDNA clone derived from rat liver, showed expression of a single mRNA species in all brain areas of identical size to 11.beta.-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, later IV), hippocampus (highest in CA3), hypothalamic medial preoptic area and arcuate nuclei and anterior pituitary. In conclusion, there is localized 11.beta.-OHSD mRNA expression and enzyme bioactivity in rat brain. The distribution of 11.beta.-OHSD corresponds to areas of reduced glucocorticoid or mineralocorticoid receptor affinity for corticosterone. Therefore 11.beta.-OHSD may regulate the access of corticosterone to cerebral mineralcorticoid and/or glucocorticoid receptors and thus modulate corticosteroid effects on brain function.