ESPE Yearbook of Paediatric Endocrinology

Brief summary: This article shows that intra-cerebroventricular injections of a recombinant adeno-associated virus expressing MKRN3 resulted in delayed puberty in female mice.MKRN3 loss-of-function mutation is the most frequent cause of familial central precocious puberty (CPP) (1).These authors investigated the effect of MKRN3 overexpression on pubertal timing, by generating a mouse model of neonatal hypothalamic Mkrn3 ov...

J Clin Invest. 2020 Aug 3;130(8):4486–4500. 10.1172/JCI136564. PMID: 32407292 https://www.jci.org/articles/view/136564In brief: This study in rats and non-human primate models investigated the mechanisms by which MKRN3 regulates pubertal onset in rats and non-human primates.Comment: Pubertal timing is in...

Elife. 2021 Sep 8;10:e69765. doi: 10.7554/eLife.69765. PMID: 34494548. https://elifesciences.org/articles/69765Brief Summary: Using a database for arcuate nucleus transcripts, this study identifies Nhlhl2 as a key regulator of the Kiss1 gene in male mice.The timing of puberty onset is i...

Brief summary: Using human induced pluripotent stem cells as well as transgenic mouse models, this paper shows that MKRN3 could initiate pubertal onset by regulating hypothalamic development and plasticity.The reactivation of GnRH secretion at puberty is thought to result from a loss in inhibitory input together with an increase in transactivation onto GnRH neurons. The main component of this inhibitory tone was incompletely understood until the discover...

Brief Summary: This cross-sectional study identifies two pathogenic variants in the Delta-like noncanonical notch ligand 1 ( DLK1 ) gene in a French cohort of 121 children with idiopathic central precocious puberty (CPP).DLK1 is a noncanonical ligand of the Delta Notch pathway known to be involved in adipocyte differentiation. Its hypothalamic expression suggests a potential role in coordinating reproductive and metabolic functions. Pathogenic v...