The brain mineralocorticoid receptor: A saga in three episodes

Marian Joels, E. Ronald de Kloet*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    84 Citations (Scopus)

    Abstract

    In 1968, Bruce McEwen discovered that H-3-corticosterone administered to adrenalectomised rats is retained in neurons of hippocampus rather than those of hypothalamus. This discovery signalled the expansion of endocrinology into the science of higher brain regions. With this in mind, our contribution highlights the saga of the brain mineralocorticoid receptor (MR) in three episodes. First, the precloning era dominated by the conundrum of two types of corticosterone-binding receptors in the brain, which led to the identification of the high-affinity corticosterone receptor as the 'promiscuous' MR cloned in 1987 by Jeff Arriza and Ron Evans in addition to the classical glucocorticoid receptor (GR). Then, the post-cloning period aimed to disentangle the function of the brain MR from that of the closely related GR on different levels of biological complexity. Finally, the synthesis section that highlights the two faces of brain MR: Salt and Stress. 'Salt' refers to the regulation of salt appetite, and reciprocal arousal, motivation and reward, by a network of aldosterone-selective MR-expressing neurons projecting from nucleus tractus solitarii (NTS) and circumventricular organs. 'Stress' is about the limbic-forebrain nuclear and membrane MRs, which act as a switch in the selection of the best response to cope with a stressor. For this purpose, activation of the limbic MR promotes selective attention, memory retrieval and the appraisal process, while driving emotional expressions of fear and aggression. Subsequently, rising glucocorticoid concentrations activate GRs in limbic-forebrain circuitry underlying executive functions and memory storage, which contribute in balance with MR-mediated actions to homeostasis, excitability and behavioural adaptation.

    Original languageEnglish
    Pages (from-to)T49-T66
    Number of pages18
    JournalJournal of endocrinology
    Volume234
    Issue number1
    DOIs
    Publication statusPublished - Jul-2017
    Event41st Annual Meeting of the International-Aldosterone-Conference (IAC) - Boston, Morocco
    Duration: 29-Apr-201630-Apr-2016

    Keywords

    • brain
    • stress
    • behavioural adaptation
    • neuronal circuits
    • mineralocorticoid receptors
    • glucocorticoid receptors
    • BROWN-NORWAY RATS
    • GLUCOCORTICOID-RECEPTOR
    • INDIVIDUAL-DIFFERENCES
    • SODIUM APPETITE
    • BLOOD-PRESSURE
    • CORTICOSTEROID RECEPTORS
    • IN-VIVO
    • DEPRESSION SUSCEPTIBILITY
    • GENE-EXPRESSION
    • STRESS-RESPONSE

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