Neuropeptide Y Y1-Receptor Stimulation Is Required for Physiological Amplification of Preovulatory Luteinizing Hormone Surges

Abstract

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 anterior pituitary gland is an obligatory event in the stimulation of spontaneous LH surges. A battery of NPY receptor agonists, as well as the specific NPY Y1 receptor antagonist BIBP3226, were used to assess the role of Y1 receptors in the amplification of LH surges. In Exp 1, the 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 = [Leu31Pro34]NPY > NPY >> hPP = rPP = NPY(13-36), which most closely reproduces the known rank-ordered affinties of these compounds for the Y1 receptor. In Exp 2, a Y1 subtype- specific antagonist, BIBP3226, was administered to unanesthetized, proestrous rats to assess the involvement of the Y1 receptor in the stimulation of spontaneous LH surges. The BIBP3226 compound strongly attenuated the endogenous proestrous LH surge, reducing the integrated value of LH secretion during the proestrous surge by more than 70%. In Exp 3, we assessed the ability of the Y1 receptor antagonist to block exogenous NPY effects on LHRH-induced LH surges. Treatment with BIBP3226 was found to completely prevent NPY amplification of LHRH-induced LH surges in pentobarbital-blocked, proestrous rats, thus confirming a pituitary locus of action of the drug. Taken together, these data clearly demonstrate that activation of neuropeptide Y receptors of the Y1 subtype is required for the physiological amplification of the spontaneous preovulatory LH surge in rats.

Estrogen-Induced μ-Opioid Receptor Internalization in the Medial Preoptic Nucleus Is Mediated via Neuropeptide Y-Y1Receptor Activation in the Arcuate Nucleus of Female Rats

“…In our hands, central injections of NPY did not inhibit lordosis; however, selective activation of the Y 1 R with LPNY inhibited lordosis. These results are congruent with the finding that Y 1 R mediates NPY actions on LH release Leupen et al, 1997;Li et al, 1999). The present results extend the observation that NPY inhibited lordosis in rats with a very robust estrogen-priming paradigm (100 g of EB) (Clark et al, 1985).…”

“…The first report of NPY in rats used a supraphysiological dose of estradiol benzoate (EB; 100 g) to induce lordosis (Clark et al, 1985), but a subsequent study repeated their findings with a more physiological relevant dose of EB (5 g), albeit in Syrian hamsters (Corp et al, 2001). Despite these results, the NPY receptor subtype mediating behavioral actions has not been elucidated; the NPY-Y 1 subtype (Y 1 R) is responsible for NPY-induced luteinizing hormone (LH) release Besecke et al, 1994;Leupen et al, 1997). This suggested that Y 1 R might be involved in reproduction.…”

The involvement of gonadotropin inhibitory hormone and kisspeptin in the metabolic regulation of reproduction

“…They also noted a negative effect of GnIH on the activity of NPY cells in mice. Of note, it has been shown that activation of the NPY-Y1 receptor is required for the physiological amplification of the spontaneous preovulatory LH surge in rats (Leupen et al 1997). Therefore, GnIH inhibition of NPY cells can also contribute to the inhibitory effect of GnIH on LH surge.…”

Attenuation of Luteinizing Hormone Surges in Neuropeptide Y Knockout Mice

“…There is considerable evidence, for example, that a preovulatory NPY surge facilitates preovulatory release of gonadotropin-releasing hormone (GnRH) in proestrous rats [1, 2], and to potentiate GnRH-induced luteinizing hormone (LH) secretion from pituitary gonadotropes [3, 4, 5, 6, 7]. These effects appear to be mediated by NPY Y1 receptors expressed in hypothalamic [8, 9]and pituitary [6]cells respectively. Other studies have demonstrated that intracerebroventricular NPY applications can induce changes in basal LH secretion in a steroid dependent manner.…”