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The role of glutamatergic mechanisms in the neuroendocrine control of reproductive maturation

Reference	D01646
Principal Investigator / Supervisor	Professor Fran Ebling
Co-Investigators / Co-Supervisors	Dr Michael Hastings
Institution	University of Cambridge
Department	Physiology Development and Neuroscience
Funding type	Research
Value (£)	124,007
Status	Completed
Type	Research Grant
Start date	03/10/1994
End date	31/03/1998
Duration	42 months

Abstract

The overall aim of this project is to understand the central mechanisms underlying transitions of fertility in mammals at puberty and in seasonal breeding. Studies funded by a current AFRC project grant have led to the working hypothesis that changes in endogenous glutamatergic activity lead to the differential secretion of gonadotrophin-releasing hormone which results in pubertal/seasonal transitions. This new proposal seeks to take advantage of the enormous and ongoing advances in the molecular biology of glutamatergic neurotransmission and to place them into a physiological context. The rationale is that given the relevance of glutamate throughout the brain, the regulation of its function and specificity are likely to be determined at the level of the receptor. Indeed, at least 18 different genes coding for various sub-units of glutamate receptor have now been cloned, and in several cases their products shown to confer selective and differential responses to their common ligand. The Siberian hamster will be the experimental subject because of he rapid and profound effects of photoperiod upon the role of NMDA-selective receptors (NMDA-R) in reproductive transitions because photoperiod induces specific changes in the response to NMDA-R activation. The initial approach will be to identify the pattern of expression of the genes coding for NMDA- R submits using both in situ hybridisation and immunocytochemistry for receptor proteins. The second aim will be to investigate their anatomical and functional relationship to the GnRH secretory system and their response to photoperiod and changes with developmental stage. Finally their role in reproductive transitions will be tested in chronic studies using conventional pharmacological approaches, and also new antisense oligonucleotide technology to achieve molecular lesions of specific receptor subunits. This study will not only enhance understanding of puberty and seasonal reproduction, but also provide information relevant to other developmental and neuroendocrine processes regulated by glutamatergic neurotransmission.

Summary

unavailable

Committee	Closed Committee - Agri-food (AF)
Research Topics	X – not assigned to a current Research Topic
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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