Central nervous system receptors involved in mediating the inhibitory action of neuropeptide Y on luteinizing hormone secretion in the male rhesus monkey (Macaca mulatta).
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 microg; 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 microg; n = 4), did not mimic the stimulatory action of 1229U91 on GnRH secretion in the juvenile male monkey. Additionally, neither NPY (200 microg; n = 2), a general Y receptor agonist, nor rPP (100 microg; 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 microg) failed to block 1229U91-induced (200 microg) GnRH release. However, the action of NPY (364 microg) in inhibiting GnRH release postpubertally was attenuated by 1229U91 (300 microg). 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.
Shahab
M
M
University of Pittsburgh School of Medicine, Department of Cell Biology and Physiology, Pittsburgh, PA 15261, USA.
Balasubramaniam
A
A
Sahu
A
A
Plant
T M
TM
D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D007276:Injections, Intraventricular; D008024:Ligands; D007986:Luteinizing Hormone / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D009919:Orchiectomy; D010456:Peptides, Cyclic / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011863:Radioimmunoassay; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*
C097287:1229U91; D008024:Ligands; D009478:Neuropeptide Y; D010456:Peptides, Cyclic; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C109491:neuropeptide Y4 receptor; D007986:Luteinizing Hormone