ESPE Yearbook of Paediatric Endocrinology

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 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...

Brief summary: A newly developed mouse model of congenital ablation of Dicer in kisspeptin neurons was used to identify a role for miRNAs in kisspeptin neuron activity and control of reproduction.The last few years have seen a shift in paradigm with the discovery of epigenetic mechanisms regulating GnRH neuron activity and thus puberty and reproduction. In particular, miRNAs appear to play a crucial role in the maturation and function of the hypothalamic...

Brief summary: Using a combination of expression studies in human embryos as well as functional studies in zebrafish and genetic sequencing of patient with congenital hypogonadotropic hypogonadism, this study identified a novel role for Jag1/Notch signaling in the development of GnRH neurons.GnRH neurons have a unique characteristic as they start life in the olfactory placode and then migrate into the hypothalamus during embryonic development, thanks to ...

Brief summary: This study identified nitric oxide synthase 1 (NOS1) heterozygous missense variants in 6 patients with hypogonadotropic hypogonadism. Altered minipuberty and puberty as well as cognitive impairment were observed in NOS1 deficient mice.Nitric oxide (NO) is produced under the control of NO synthase in hypothalamic neurons. NO plays a crucial role in regulating gonadotropin-releasing hormone (GnRH) secretion, acting as a strong inhibitory sig...

Brief summary: This literature review summarized the recent advances in our understanding of the GnRH system throughout life and its implication in the brain development beyond its conventional role in reproductive control.During embryonic development GnRH neurons migrate from the olfactory placode to the hypothalamus, where they control the hypothalamus–pituitary–gonadal axis (1,2). But many GnRH neurons migrate to other brain regions, such as...