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Y1 receptor activation is involved in the effect of exogenous neuropeptide Y on pup growth and the early termination of lactational diestrus in the postpartum rat.

Abstract
The effect of chronic administration of exogenous neuropeptide Y (NPY) and specific NPY receptor agonists and antagonists on reproductive function was examined in lactating rats. As previously demonstrated in our laboratory, chronic (7-day) intracerebroventricular (i.c.v.) NPY infusion (6 microg/day) from days 8-15 postpartum (pp) caused a significant decrease in milk production and an early termination of lactational diestrus. Similar application of the mixed Y1/Y4/Y5 receptor agonist (Leu31, Pro34) NPY (at 3, 6 and 9 microg/day) reproduced the effect of chronic NPY infusion on milk production in a dose-independent manner. Consistent with this effect, the potent Y1 antagonist/Y4 agonist, 1229U91, given concomitantly with NPY eliminated the decline in milk production. The Y2 receptor agonist, NPY13-36, had no effect on milk production at any of the doses used. Length of lactational diestrus was reduced following administration of the Y2 agonist at 18 microg/day but not at 9 microg or 27 microg/day whereas (Leu31, Pro34) NPY infusion had no effect on this parameter at any of the doses used. However, the group that was treated with NPY plus 1229U91 exhibited the usual length of lactational diestrus, indicating that there is at least some Y1 involvement in the effects of NPY on lactational infertility. To test the possibility that the effects of NPY infusion are mediated through changes in circulating prolactin and progesterone, plasma concentrations of these hormones were measured on day 15 pp in NPY-, (Leu31, Pro34) NPY- and vehicle-treated females. NPY-infused females had lower plasma prolactin concentrations than vehicle-infused dams but progesterone concentrations were similar across groups. Overall, these data indicate that chronic exogenous NPY-infusion in lactating females disrupts milk production and shortens lactational diestrus, most likely through reducing prolactin secretion, and that this effect is mediated via Y1 receptor activity.
AuthorsD J Toufexis, S Yorozu, B Woodside
JournalJournal of neuroendocrinology (J Neuroendocrinol) Vol. 14 Issue 5 Pg. 354-60 (May 2002) ISSN: 0953-8194 [Print] United States
PMID12000540 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 1229U91
  • Drug Combinations
  • Neuropeptide Y
  • Neuropeptides
  • Peptides, Cyclic
  • Receptors, Neuropeptide Y
  • neuropeptide Y-Y1 receptor
  • neuropeptide Y, Leu(31)-Pro(34)-
  • Progesterone
  • Prolactin
Topics
  • Animals
  • Animals, Newborn (anatomy & histology, growth & development, physiology)
  • Body Weight (drug effects)
  • Diestrus (drug effects, physiology)
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Eating (drug effects)
  • Female
  • Lactation (drug effects, physiology)
  • Neuropeptide Y (analogs & derivatives, pharmacology)
  • Neuropeptides (antagonists & inhibitors)
  • Peptides, Cyclic (pharmacology)
  • Postpartum Period (drug effects, physiology)
  • Progesterone (blood)
  • Prolactin (blood)
  • Rats
  • Rats, Wistar
  • Receptors, Neuropeptide Y (agonists, physiology)

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