Evidence for involvement of neuropeptide Y and melanocortin systems in the hyperphagia of lactation in rats.
Hypothalamic neuropeptide Y (NPY) systems are upregulated during lactation in rats. Because NPY is central to the hypothalamic control of energy balance, the present studies tested the hypothesis that NPY contributes to the marked hyperphagia during lactation. A 4-day infusion of [D-tyr (27,36), D-thr (32)] NPY (27-36) (D-NPY(27-36)), a peptide analogue of NPY that antagonizes NPY-induced feeding, into the third ventricle at 1 microg/h transiently inhibited nocturnal feeding in nonlactating female rats. However, this antagonist had no effect on nocturnal feeding, but did transiently reduce food intake during the light hours, when infused into the third ventricle at the same dose in lactating females. An essentially similar pattern of results was obtained with chronic infusion into the third ventricle of the anorexigenic peptide alpha-melanocyte-stimulating hormone (alpha-MSH, 1 microg/h), in nonlactating and lactating rats. Both D-NPY(27-36) and alpha-MSH transiently reduced nocturnal food intake in lactating rats by approximately 10% when infused at the higher dose of 5 microg/h, and a marked inhibition of approximately 40% of both nocturnal and diurnal feeding was produced by a combined infusion of both at 5 microg/h. These results provide the first pharmacological evidence implicating specific neuromessengers in mediating the hyperphagia of lactation, and suggest that, while an action of NPY may contribute to the increased food intake seen in lactating animals, other systems are also involved. In particular, a reduction in melanocortin signaling during lactation may allow for an increased orexigenic influence of the agouti-related protein (AgRP), which is co-expressed with NPY.
Crowley
William R
WR
Department of Pharmacology and Toxicology, University of Utah College of Pharmacy, 30 South 2000 East, Room 201, Salt Lake City, UT 84112, USA. william.crowley@deans.pharm.utah.edu
Ramoz
Gina
G
Hurst
Brianne
B
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003624:Darkness; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005260:Female; D006963:Hyperphagia / Q000523:psychology*; D007276:Injections, Intraventricular; D007774:Lactation / Q000523:psychology*; D008027:Light; D009478:Neuropeptide Y / Q000819:agonists / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013238:Stereotaxic Techniques; D000521:alpha-MSH / Q000494:pharmacology / Q000502:physiology*
D009478:Neuropeptide Y; D010446:Peptide Fragments; C079216:PYX 2; D000521:alpha-MSH