Aims: To define the ultradian pattern of corticosterone secretion in the rat, how this may be altered in different physiological states and the relevance of these patterns to nuclear signalling in the hippocampus.
Methods: Rats were cannulated and attached to our automated blood sampling system. Some rats had simultaneous intracranial microdialysis for free corticosterone in the hippocampus and other rats were adrenalectomised and corticosterone replaced by automated intravenous infusion. Corticosterone was measured by radioimmunoassay and glucocorticoid receptor (GR) and mineralocorticoid (MR) translocation in the hippocampus assessed by subcellular fractionation of nuclear and cytoplasmic fractions and Western blotting.
Results: Rats have an approximate hourly ultradian pattern of corticosterone release, amplification of which results in the classic circadian rhythm. This pattern shows sexual dimorphism, changes with age and is responsive to inflammation and lactation. Pulses of corticosterone in the blood are paralleled by tissue levels of free corticosterone in the brain. Each pulse results in a rapid translocation of both MR and GR to the nucleus. The rate of clearance of MR and GR from the nucleus are however very different, with MR remaining at high levels for over sixty minutes (the interpulse interval) and nuclear GR falling rapidly within thirty minutes. This rapid depletion of GR was blocked by the ICV infusion of MG-132, a specific irreversible inhibitor of 26S proteasome.
Conclusions: The rapid turnover of activated nuclear GR provides a mechanism for tissues to respond to the different patterns of corticosterone pulsatility seen in different physiological and pathological states.