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Investigating the role of the G-protein coupled receptor GPR54 in regulating the mammalian reproductive axis.

Reference	BB/C003861/1
Principal Investigator / Supervisor	Professor William Colledge
Co-Investigators / Co-Supervisors
Institution	University of Cambridge
Department	Physiology Development and Neuroscience
Funding type	Research
Value (£)	279,709
Status	Completed
Type	Research Grant
Start date	01/09/2005
End date	31/08/2008
Duration	36 months

Abstract

At puberty, pulsatile secretion of gonadotrophin releasing hormone (GnRH) from the hypothalamus stimulates gonadotrophin release from the anterior pituitary to initiate sexual maturation of the gonads. We have found that GPR54, a G-protein coupled receptor is required for pubertal sexual development. Mice lacking this receptor fail to undergo puberty and have low circulating levels of sex steroids and gonadotrophins. Administration of exogenous gonadotrophins indicates that ovarian and pituitary responses are preserved in these mice and mutant animals have normal levels of GnRH in the hypothalamus. Thus, GPR54 is required for the normal function of the hypothalamic-pituitary-gonadal axis, most likely at the level of GnRH secretion. While we have established a central role for GPR54 in the initiation of puberty, the precise mechanism by which this receptor functions is not known. A peptide ligand (kisspeptin) for the GPR54 receptor has been identified by the physiological role of this peptide remains to be defined. This project will determine the mechanism of action of the GPR54 receptor in puberty by defining and specific cell types that express this receptor in the hypothamic-pituitary axis and establishing whether GnRH secretion is defective in the mutant mice. We will also define the role the kisspeptin plays in stimulating GnRH release and whether this is by direct stimulation of GnRH neurons or indirectly via other neuronal cell types. These studies will provide a more detailed understanding of this new control point in the mammalian reproductive axis, and may have important implications for the diagnosis and therapy of reproductive disorders and the development of novel contraceptives.

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	Industrial Partnership Award (IPA)

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