Neuropeptide Y (Npy): A Possible Role in the Initiation of Puberty

Abstract

NPY modulates the rat hypothalamic-pituitary-gonadal axis at both the adenohypophysial and central levels. Previously published studies have consistently shown elevations of GnRH content in the preoptic area (POA) and hypothalamus starting with the appearance of GnRH immunoreactivity around fetal day 12-14 until stabilization around the time of puberty. In the present studies, irNPY content of male and female rat hypothalami and POA was examined during days 0 to 36 of postnatal development. Hypothalamic irNPY content rose steadily from 4.54 +/- 0.19 ng/fragment (males) and 2.72 +/- 0.55 ng/fragment (females) at birth to 34.14 +/- 3.94 ng/fragment (males) and 46.79 +/- 6.16 ng/fragment (females) at day 36, corresponding approximately to the time of vaginal opening. A similar elevation of irNPY content was observed in the POA. At day 0, POA content was 1.91 +/- 0.18 ng/fragment (males) and 2.02 +/- 0.25 ng/fragment (females) and progressively increased to 42.26 +/- 3.94 ng/fragment and 41.33 +/- 3.72 ng/fragment by postnatal day 36. In subsequent investigations, hypophysial-portal and peripheral plasma irNPY was determined around the time of vaginal opening, revealing a surge in portal levels of irNPY which preceded the prepubertal LH surge. The progressive postnatal increase in hypothalamic and POA irNPY content culminating in a prepubertal surge of irNPY secretion into the hypophysial-portal circulation suggests involvement of this neuropeptide in reproductive development and the onset of puberty.

Prepubertal increases in gonadotropin-releasing hormone mRNA, gonadotropin-releasing hormone precursor, and subsequent maturation of precursor processing in male rats.

“…During the infantile period immunoreactive NPY levels in the POA increase until weaning, whereupon the levels are maintained throughout the juvenile period (44). This may therefore be responsible for the increase in GnRH biosynthesis observed in our study after day 21.…”

“…NPY may be an affector of GnRH biosynthesis and release both before and during puberty onset (44). During the infantile period immunoreactive NPY levels in the POA increase until weaning, whereupon the levels are maintained throughout the juvenile period (44).…”

The adolescent brain and age-related behavioral manifestations

“…[48] for review). While chronic administration of NPY has been reported to delay sexual maturation in rats [222,424], other research has shown that levels of NPY increase during the prepubertal to pubertal period in rats and rhesus monkeys [207,537], with NPY antiserum decreasing the magnitude of the GnRH surge in pubertal rats [367] and monkeys, but not prepubertal monkeys [207]. Part of the complexity of studying the interaction of NPY (as well as opiates) with the hypothalamic gonadostat around the time of puberty is that these peptides may exert opposite influences on GnRH release depending on gonadal hormone levels [222], with levels of these gonadal steroids (and potentially the receptor systems responsive to these steroids) changing substantially during the course of puberty.…”

Gonadotropin-Releasing Hormone and NMDA Receptor Gene Expression and Colocalization Change during Puberty in Female Rats

“…Because the GnRH neurosecretory system is already morphologically and functionally mature long before the onset of puberty Goldsmith and Song, 1987), it is probable that changes in inputs to the GnRH system are responsible for the increase in pulsatile GnRH release that ultimately results in the attainment of adult reproductive function. For example, increases in stimulatory inputs from noradrenergic (Advis et al, 1978;Raum et al, 1980;Gore and Terasawa, 1991), neuropeptide Y (Sutton et al, 1988;Minami et al, 1990;Gore et al, 1993;Gruaz et al, 1993), and glutamatergic (Gay and Plant, 1987;Urbanski and Ojeda, 1990) neurons precede the onset of puberty. Similarly, a decrease in inhibition from GABAergic neurons probably also contributes to the timing of puberty (Mitsushima et al, 1994).…”