Neurobiological Mechanisms of the Onset of Puberty in Primates*

Abstract

An increase in pulsatile release of LHRH is essential for the onset of puberty. However, the mechanism controlling the pubertal increase in LHRH release is still unclear. In primates the LHRH neurosecretory system is already active during the neonatal period but subsequently enters a dormant state in the juvenile/prepubertal period. Neither gonadal steroid hormones nor the absence of facilitatory neuronal inputs to LHRH neurons is responsible for the low levels of LHRH release before the onset of puberty in primates. Recent studies suggest that during the prepubertal period an inhibitory neuronal system suppresses LHRH release and that during the subsequent maturation of the hypothalamus this prepubertal inhibition is removed, allowing the adult pattern of pulsatile LHRH release. In fact, y-aminobutyric acid (GABA) appears to be an inhibitory neurotransmitter responsible for restricting LHRH release before the onset of puberty in female rhesus monkeys. In addition, it appears that the reduction in tonic GABA inhibition allows an increase in the release of glutamate as well as other neurotransmitters, which contributes to the increase in pubertal LHRH release. In this review, developmental changes in several neurotransmitter systems controlling pulsatile LHRH release are extensively reviewed.

Altered Gene Expression Profiles of the Hypothalamic Arcuate Nucleus of Male Mice Suggest Profound Developmental Changes in Peptidergic Signaling

“…Although pubertal development is preceded by reduced hypothalamic GABA release [9,10,77], the three GABAergic markers Gad1 , Gad2 and Slc32a1 (encoding for vesicular inhibitory amino acid transporter) did not change. This finding is reminiscent of the lack of difference in ARC Gad1 and Gad2 transcript levels between the infantile and pubertal stages in the male monkey [65].…”

“…Puberty can take place gonad independently [5] with the activation of hypothalamic gonadotropin-releasing hormone (GnRH) neurons [1,2,3], leading to the onset of pulsatile GnRH secretion into the hypophyseal portal circulation. Neuronal and glial signals that play either causal or permissive roles in puberty initiation are multiplex and include increased levels of peripheral leptin [6], enhanced central glia-to-neuron signaling [7], reduced central inhibitory neuropeptide Y (NPY) tone [8] and, in particular, reduced hypothalamic GABA release [9,10] followed by increased glutamate [9,11,12,13] release. Peptide and amino acid neurotransmitters synthesized and/or acting in the hypothalamic arcuate nucleus (ARC) are critically involved in pubertal development.…”

Neuroanatomy of the Human Hypothalamic Kisspeptin System

“…Further neurotransmitters acting upstream from KP cells possibly include glutamate which can induce the bursting activity of KP neurons [110]. The glutamatergic regulation of KP neurons may also be critically involved in the onset of puberty [111]. …”

New Causes of Central Precocious Puberty: The Role of Genetic Factors

“…The reemergence of pulsatile GnRH secretion leads to increases in the secretion of the gonadotropins and of the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the anterior pituitary gland and to the consequent activation of the gonadal function [1]. …”