Behind the scenes: epigenetic mechanisms rule the roost in pubertal timing

In humans, following a mysterious quiescence during childhood, the reactivation of pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus marks the onset of puberty. 1 Balasubramanian R Crowley Jr, WF Isolated GnRH deficiency: a disease model serving as a unique prism into the systems biology of the GnRH neuronal network. Mol Cell Endocrinol. 2011; 346: 4-12 Crossref PubMed Scopus (46) Google Scholar The precise molecular triggers that govern this dynamic developmental transition remain elusive. Early reactivation of pulsatile GnRH secretion presents clinically as central precocious puberty. Over the past two decades, genetic studies in central precocious puberty have begun to shed light into the crucial molecular determinants that reactivate pulsatile GnRH secretion in humans. 2 Argente J Dunkel L Kaiser UB et al. Molecular basis of normal and pathological puberty: from basic mechanisms to clinical implications. Lancet Diabetes Endocrinol. 2023; 11: 203-216 Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar However, the full genetic architecture of central precocious puberty and full ensemble of genes contributing to the cause of central precocious puberty remain unclear, especially in sporadic central precocious puberty presentations. Hence, genetic investigation of central precocious puberty provides a unique opportunity to unravel the molecular drivers governing the initiation of puberty. Rare variants in the MECP2 gene in girls with central precocious puberty: a translational cohort studyWe identified rare MECP2 variants in girls with central precocious puberty, with or without mild neurodevelopmental abnormalities. MECP2 might have a role in the hypothalamic control of human pubertal timing, adding to the evidence of involvement of epigenetic and genetic mechanisms in this crucial biological process. Full-Text PDF