NEUROPEPTIDE-Y Y1-RECEPTOR STIMULATION IS REQUIRED FOR PHYSIOLOGICAL AMPLIFICATION OF PREOVULATORY LUTEINIZING-HORMONE SURGES

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.