Brain mineralocorticoid receptors and centrally regulated functions

Mineralocorticoid receptors (MRs) expressed in limbic neurons, notably of h ippocampus, retain both aldosterone and corticosterone. Basal concentration s of corticosterone already substantially occupy the limbic MR type, sugges ting that in hippocampal neurons, MR activity rather than ligand bioavailab ility is rate limiting. The periventricular region expresses MRs involved i n the control of salt homeostasis, which are aldosterone selective because of the presence of 11 beta-hydroxy-steroid dehydrogenase. MR is in hippocam pal CA1, CA2, and dentate gyrus colocalized with glucocorticoid receptors ( GRs). Both receptor types mediate in a coordinate manner the corticosterone action on information processing critical for behavioral adaptation and as sociated neuroendocrine responses to stress. MRs operate in proactive mode determining the sensitivity of the stress response system, while GRs facili tate recovery from stress in reactive mode. On the neuronal level, MR-media ted action maintains a stable excitatory tone and attenuates the influence of modulatory signals. In contrast, GR-mediated effects suppress excitabili ty transiently raised by excitatory stimuli. MR is also involved in control of autonomic outflow and volume regulation. This was demonstrated by the e ffect of an MR antagonist, which was administered centrally, because mdr P- glycoproteins hamper the access of synthetic steroids to the brain. The MR antagonist attenuates presser responses to a stressor, such as experienced during tail sphygmography. Diuresis and urinary electrolyte excretion are i ncreased after the MR antagonist, but this effect is abolished after bilate ral denervation of the kidney. It is presently unknown in which brain cells the MR-mediated effects on these aspects of central cardiovascular regulat ion occur.