11 beta-hydroxysteroid dehydrogenase functions reversibly as an oxidoreductase in the rat hippocampus in vivo

The localization in the brain and metabolism of H-3-labeled corticosterone (B) and 11-dehydrocorticosterone (A) of high specific radioactivity was det ermined after stereotaxic injection into the hippocampus of anesthetized ra ts. [H-3]B was cleared very rapidly with, on average, only about 7% being r ecovered after 5 min and 0.5% after 30 min. Most of this H-3-radioactivity was localized in the area surrounding the site of injection with little dif fusion to adjacent areas. These findings make it possible to compare the sh ort term metabolism of [H-3]A and [H-3]B in different lobes of the hippocam pus in the same animal and establish their local equilibrium point in vivo. Under these conditions, about 5% conversion of each steroid to the other w as observed in contrast to the situation in cultured hippocampal cells wher e 11 beta-hydroxysteroid dehydrogenase (II-HSD) has been shown by others to act primarily as a reductase catalyzing the conversion of A to B. This met hod can also be used to study the effect of inhibitors such as 11 alpha-hyd roxyprogesterone, applied locally in the brain, on the metabolism of cortic osteroids. The rate of conversion [H-3]B or [H-3]A to their dihydro- and te trahydro-derivatives capable of modulating the GABA(a) receptor in the hipp ocampus was much lower than their interconversion. Thus, factors which infl uence the direction of the 11-HSD catalyzed reaction are important in regul ating not only salt appetite and blood pressure but also the levels of neur oactive metabolites of corticosterone. (C) 2000 Elsevier Science Ltd. All r ights reserved.