SFEBES2008 Symposia System-specific effect steroids (4 abstracts)
Glucocorticoid signalling in the brain
Stafford Lightman 1 , Helen Atkinson 1 , Susanne-Katrin Droste 1 , Michael Harbuz 1 , Ronald de Kloet 2 , Astrid Linthorst 1 , Mervyn McKenna 1 , Johannes Reul 1 , Josephine Seale 1 , Crispin Wiles 1 , Susan Wood 1 & Becky Conway-Campbell 1
1University of Bristol, Bristol, UK; 2University of Leiden, Leiden, The Netherlands.
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.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more