Sm. Leupen et al., NEUROPEPTIDE-Y Y1-RECEPTOR STIMULATION IS REQUIRED FOR PHYSIOLOGICAL AMPLIFICATION OF PREOVULATORY LUTEINIZING-HORMONE SURGES, Endocrinology, 138(7), 1997, pp. 2735-2739
Neuropeptide Y (NPY) has been shown to potentiate the actions of LHRH
during the generation of preovulatory LH surges. It is not yet known,
however, if activation of a specific subtype of NPY receptors in the a
nterior pituitary gland is an obligatory event in the stimulation of s
pontaneous LK surges. A battery of NPY receptor agonists, as well as t
he specific NPY Y1 receptor antagonist BIBP3226, were used to assess t
he role of Y1 receptors in the amplification of LH surges. In Exp 1, t
he potencies of a number of NPY agonists in facilitating LHRH-induced
LH surges were assessed in pentobarbital (PB)-blocked, proestrous rats
. The rank-ordered potencies of these compounds were determined to be
PYY = [Leu(31)Pro(34)]NPY > NPY much greater than hPP = rPP - NPY(13-3
6), which most closely reproduces the known rank-ordered affinties of
these compounds for the Y1 receptor. In Exp 2, a Y1 subtype-specific a
ntagonist, BIBP3226, was administered to unanesthetized, proestrous ra
ts to assess the involvement of the Y1 receptor in the stimulation of
spontaneous LH surges. The BIBP3226 compound strongly attenuated the e
ndogenous proestrous LK surge, reducing the integrated value of LH sec
retion during the proestrous surge by more than 70%. In Exp 3, we asse
ssed the ability of the Y1 receptor antagonist to block exogenous NPY
effects on LHRH-induced LK surges. Treatment with BIBP3226 was found t
o completely prevent NPY amplification of LHRH-induced LH surges in pe
ntobarbital-blocked, proestrous rats, thus confirming a pituitary locu
s of action of the drug. Taken together, these data clearly demonstrat
e that activation of neuropeptide ii receptors of the Y1 subtype is re
quired for the physiological amplification of the spontaneous preovula
tory LH surge in rats.