Premium
Central Nervous System Receptors Involved in Mediating the Inhibitory Action of Neuropeptide Y on Luteinizing Hormone Secretion in the Male Rhesus Monkey ( Macaca mulatta )
Author(s) -
Shahab M.,
Balasubramaniam A.,
Sahu A.,
Plant T. M.
Publication year - 2003
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1046/j.1365-2826.2003.01085.x
Subject(s) - medicine , endocrinology , neuropeptide y receptor , agonist , hypothalamus , biology , luteinizing hormone , receptor , gonadotropin releasing hormone , neuropeptide , hormone
An earlier finding that gonadotropin‐releasing hormone (GnRH) secretion may be triggered prematurely in the juvenile male monkey by central administration of 1229U91, a Y1 receptor antagonist, contributed to our current hypothesis that neuropeptide Y (NPY) is a major component of the brake that holds pulsatile GnRH release in check during prepubertal development in primates. However, 1229U91 is also a Y4 receptor agonist, and the present study was conducted to further examine the role of the Y1 receptor in mediating the putative inhibitory action of NPY on GnRH release. Agonadal juvenile and postpubertal male monkeys were implanted with i.v. and i.c.v. cannulae to gain continuous access to the venous and cerebroventricular circulations without sedation. Luteinizing hormone (LH) secretion was measured to provide an indirect index of GnRH release. The specific Y1 antagonists, VD‐11 (476 µg; n = 4) and isopropyl 3‐chloro‐5‐[1‐({6‐[2‐(5‐ethyl‐4‐methyl‐1,3‐thiazol‐2‐yl)ethyl]‐4‐morpholin‐4‐ylpyridin‐2‐yl}amino)ethyl]phenylcarbamate (Compound A, 300 µg; n = 4), did not mimic the stimulatory action of 1229U91 on GnRH secretion in the juvenile male monkey. Additionally, neither NPY (200 µg; n = 2), a general Y receptor agonist, nor rPP (100 µg; n = 4), a Y4 agonist, mimicked the action of 1229U91 in stimulating GnRH release. Moreover, previous exposure of the hypothalamus of juvenile monkeys (n = 5) to NPY (660 µg) failed to block 1229U91‐induced (200 µg) GnRH release. However, the action of NPY (364 µg) in inhibiting GnRH release postpubertally was attenuated by 1229U91 (300 µg). We conclude that, although the action of exogenous NPY to suppress GnRH release from the postpubertal hypothalamus appears to be mediated, at least in part, by the Y1 receptor, the existence of a Y1 receptor pathway inhibitory to GnRH release in the prepubertal hypothalamus remains to be substantiated.