Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2009) 20 S7.3

ECE2009 Symposia Glucocorticoid action in the brain (4 abstracts)

Genomic versus nongenomic corticosteroid effects

Marian Joels & Henk Karst


University of Amsterdam, Amsterdam, The Netherlands.


Neurons in the CA1 region of the rodent hippocampus express high levels of the nuclear mineralocorticoid (MR) and glucocorticoid receptors (GR). The MR affinity is such that low levels of corticosterone -as seen under rest- already substantially activate this receptor. Hence, for many years the GR was considered to be the main mediator of the stress response. This receptor causes (among other things) a delayed enhanced influx of calcium into CA1 neurons, an enhancement of serotonin responses and an impaired ability to induce long-term potentiation. Overall, these actions help to normalize hippocampal activity several hours after stress and to preserve information encoded shortly after stress. Recently, it has become evident that this delayed normalizing effect is complemented by a rapid nongenomic action of the same hormone. Thus, as soon as corticosteroid levels rise, hippocampal cells show an increased release probability of glutamate-containing synaptic vesicles. This is presumably due to MRs inserted into the presynaptic membrane, linked to the ERK1/2 signaling pathway. Interestingly, membrane-located MRs display a 10-fold lower affinity than their nuclear counterpart, allowing the former to be a prominent player in the stress response. MRs can also be inserted into the postsynaptic membrane and then (via G-proteins) mediate a rapid suppression of the K-conductance IA. Overall, these rapid and quickly reversible effects of corticosterone are expected to raise hippocampal excitability (in concert with other stress hormones) as long as the hormone levels are elevated, thus enabling the early stages of memory formation. Preliminary evidence suggests that both the nongenomic and the genomic effects of corticosterone show regional differentiation. This allows for region-specific facilitation or attenuation of neuronal activity, which is important for the role of the various areas in the neuroendocrine / cognitive processing of stressful information.

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