ENDOCRINOLOGY AND ADOLESCENCE: Deciphering puberty: novel partners, novel mechanisms

Abstract

Puberty is a fascinating developmental phase that involves the attainment of reproductive capacity and the completion of sexual and somatic maturation. As a life-changing event, puberty onset is precisely controlled by interconnected regulatory pathways that are sensitive to numerous endogenous signals and environmental cues. The mechanisms of normal puberty and its potential deviations have been thoroughly studied in humans and model species. Yet, characterization of the neurobiological basis of puberty is still incomplete. Progress on this front is not only relevant from a physiological perspective but would also help to unravel the underlying causes for the observed changes in the timing of puberty in humans, with a trend for earlier puberty onset, especially in girls. In this review, we will provide a synoptic overview of some recent developments in the field that have deepened our understanding of the neuroendocrine and molecular basis for the control of puberty onset. These include not only the demonstration of the involvement of the hypothalamic Kiss1 system in the control of puberty and its modulation by metabolic cues but also the identification of the roles of other neuropeptide pathways and molecular mediators in the regulation of puberty. In addition, the potential contribution of novel regulatory mechanisms, such as epigenetics, in the central control of puberty will be briefly discussed. Characterization of these novel players and regulatory mechanisms will improve our understanding of the basis of normal puberty and its eventual alterations in various pathological conditions. European Journal of Endocrinology 167 733-747

Daily successive changes in reproductive gene expression and neuronal activation in the brains of pubertal female mice

“…Indeed, it has been proposed that upstream networks may control puberty through the relief of inhibition on stimulatory factors, like kisspeptin and NKB, to allow GnRH secretion to be enhanced at puberty (Kauffman, 2010; Lomniczi et al, 2013; Tena-Sempere, 2012; Terasawa et al, 2013). Based on our current findings, RFRP-3 signaling may be one possible aspect of inhibitory control during puberty onset.…”

“…Several upstream hypothalamic circuits have been implicated in the control and modulation of GnRH secretion, but how and when these various reproductive circuits change during development to potentially time and trigger pubertal GnRH secretion is poorly understood (Kauffman, 2010; Ojeda et al, 2006, 2010; Richter, 2006; Tena-Sempere, 2012; Terasawa et al, 2013). Recognized upstream regulators of GnRH neurons range from stimulatory systems, like kisspeptin and neurokinin B (NKB), to inhibitory systems, such as GABA and RFRP-3 (the mammalian homolog of GnIH), not to mention epigenetic factors (Lomniczi et al, 2013; Semaan and Kauffman, 2013).…”

Epigenetics: A New Player in the Regulation of Mammalian Puberty

“…Conversely, when Eed was overexpressed, Kiss1 expression dropped, GnRH response was blunted, and pubertal developmental was delayed. The studies by Lomniczi et al [43] and others [24,42,87] need to be replicated and expanded, but they clearly represent a step forward in our understanding of the regulation of puberty and provide an important construct for future studies. Interpretation of mechanism Initiation of puberty requires repression of repressors AZA data derive from Lomniczi et al [43], SAHA and L-MET data derive from Rzeczkowska et al [24], and +/-LSD1 data derive from Gill et al [42].…”

Validity of Self-Assessment of Pubertal Maturation

“…4 The age at pubertal onset varies between genders and individuals and is known to be influenced by many factors such as ethnicity, nutrition, genetics, and environment. [5][6][7][8] For clinical or epidemiologic studies in which exact pubertal stages are required, many aspects must be taken into consideration. Some children may feel uncomfortable with the physical examination, and individual assessments are time consuming, logistically challenging, and expensive in large populations.…”