Brain mineralocorticoid receptors and centrally regulated functions.
Mineralocorticoid receptors (MRs) expressed in limbic neurons, notably of hippocampus, retain both aldosterone and corticosterone. Basal concentrations of corticosterone already substantially occupy the limbic MR type, suggesting that in hippocampal neurons, MR activity rather than ligand bioavailability is rate limiting. The periventricular region expresses MRs involved in the control of salt homeostasis, which are aldosterone selective because of the presence of 11beta-hydroxysteroid dehydrogenase. MR is in hippocampal 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 associated neuroendocrine responses to stress. MRs operate in proactive mode determining the sensitivity of the stress response system, while GRs facilitate recovery from stress in reactive mode. On the neuronal level, MR-mediated action maintains a stable excitatory tone and attenuates the influence of modulatory signals. In contrast, GR-mediated effects suppress excitability transiently raised by excitatory stimuli. MR is also involved in control of autonomic outflow and volume regulation. This was demonstrated by the effect 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 pressor responses to a stressor, such as experienced during tail sphygmography. Diuresis and urinary electrolyte excretion are increased after the MR antagonist, but this effect is abolished after bilateral denervation of the kidney. It is presently unknown in which brain cells the MR-mediated effects on these aspects of central cardiovascular regulation occur.
de Kloet
E R
ER
Leiden/Amsterdam Center for Drug Research, Leiden, The Netherlands. e.kloet@lacdr.leidenuniv.nl
Van Acker
S A
SA
Sibug
R M
RM
Oitzl
M S
MS
Meijer
O C
OC
Rahmouni
K
K
de Jong
W
W
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology; D009490:Neurosecretory Systems / Q000502:physiology; D018161:Receptors, Mineralocorticoid / Q000378:metabolism / Q000502:physiology*; D011987:Receptors, Steroid / Q000378:metabolism
D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid