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This version published online on November 4, 2004
Endocrinology, doi:10.1210/en.2004-1085
A more recent version of this article appeared on February 1, 2005
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Submitted on August 19, 2004
Accepted on October 25, 2004

Y2 receptor-selective agonist delays the estrogen-induced LH surge in ovariectomised ewes but Y1-receptor-selective agonist stimulates voluntary food intake

Iain J. Clarke*, Kathryn Backholer, and Alan J Tilbrook

Prince Henry's Institute of Medical Research, Clayton, Melbourne, Victoria 3168, Australia; Department of Physiology, Monash University, Melbourne, Australia

* To whom correspondence should be addressed. E-mail: iain.clarke{at}phimr.monash.edu.au.

Neuropeptide Y (NPY) plays a major role in the regulation of food intake, regulation of homeostasis and neuroendocrine function. We have previously shown that third ventricular infusion of this peptide delays the estradiol benzoate (EB)-induced surge in luteinising hormone (LH) secretion in ovariectomised (OVX) ewes. To determine the receptor subtype that transmits this effect, we have now used the same model to infuse a Y1 receptor agonist [NPY Leu31 Pro34], a Y2 receptor agonist (PYY3-36), and a Y4 receptor agonist (Pancreatic Polypeptide; PP). We monitored the surges in animals given these agonists or artificial cerebrospinal fluid by measuring plasma LH levels and we also measured daily voluntary food intake (VFI). A low (7 µg/h) dose of Y2 agonist delayed the surge but did not affect VFI, whereas a higher dose (14 µg/h) also stimulated VFI. A dose of 18 µg/h of the Y1 agonist did not affect surge generation, but stimulated VFI. A dose of 24 µg/h of Y4 agonist affected neither surge generation nor VFI. These specificities are different to those reported for the rat and the human (in which a Y2 agonist causes reduction in VFI). We conclude that, in sheep, the negative regulation of the reproductive axis by NPY and Y-receptor agonists is effected via the Y2 receptors whereas the orexigenic effects are most likely effected via the Y1 receptors.


Key words: Y4 agonist • reproduction • appetite • neuropeptide Y




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