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The importance of pulsatile secretion for glucocorticoid signalling

Reference	BB/C51297X/1
Principal Investigator / Supervisor	Professor Stafford Lightman
Co-Investigators / Co-Supervisors	Dr Michael Norman
Institution	University of Bristol
Department	Henry Wellcome LINE
Funding type	Research
Value (£)	383,743
Status	Completed
Type	Research Grant
Start date	26/06/2005
End date	25/07/2008
Duration	37 months

Abstract

Pulsatile signals provide a dual mechanism for the regulation of target tissue responses. Although this had been well recognised in neural signalling and also in the gonadotrophin and GH signalling systems of the endocrine system, its relevance to nuclear receptor signalling has not been investigated. The use of frequency modulation can provide an additional mode of signalling which also has potential for tissue specificity. We have developed an automated sampling system that has allowed us to define a quite remarkable ultradian rhythmicity of corticosterone secretion in the rat which has diurnal variation and which changes markedly in situations of acute and chronic stress. The physiological relevance of these pulses is however totally unknown. We have therefore adapted our sampling system so that we can artificially create different patterns of corticosterone pulsatility. We should now like to refine this apparatus and use it to model different patterns of corticosterone secretion. This will allow us to look at the effect of different ultradian rhythms on glucocorticoid responsive genes in the brain and periphery and to define differential effects on mineralo- and gluco-corticoid receptor translocation and DNA binding. We shall then use specialist analyses of expression profiling to look at differential patterns of corticosteroid-dependent gene expression in rat strains which have genetically determined differences in their profiles of corticosterone secretion and in their stress responsiveness.

Summary

unavailable

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	Neuroscience and Behaviour
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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