Acceleration of pubertal development following central blockade of the Y1 subtype of neuropeptide Y receptors

Pubertal development results from the coordinate secretion of gonadotropin-releasing hormone (GnRH) by hypothalamic GnRH neurons. Central administration of neuropeptide Y (NPY) to prepubertal rats can indefinitely delay sexual maturation by inhibiting this GnRH secretion. The aim of the present study was to further investigate the physiological role of NPY in pubertal development, and to assess the potential involvement of its Y1 receptor subtype in this setting. The timing of pubertal development was determined in juvenile female rats receiving chronic i.c.v. infusion of a specific Y1 receptor antagonist (BIBP 3226), and compared with controls. Although treatment with BIBP 3226 did not affect the age at vaginal opening, animals receiving the Y1 antagonist experienced a quicker progression through puberty, corroborated by a significant increase in pituitary luteinizing hormone content. This effect of BIBP3226 on the gonadotrope axis occurred without apparent toxicity, but was accompanied by a transient decrease in body weight gain on the first day of treatment, suggesting an effect on appetite. Together, our results add to the evidence in favour of a role for NPY in the onset of puberty. They are entirely consistent with the proposed inhibition exerted by endogenous hypothalamic NPY before the onset of pubertal development. They also suggest that the Y1 subtype of NPY receptors is involved in this effect. (C) 2000 Elsevier Science B.V. All rights reserved.