Bassi Ivan, ANDRé Valentina, Marelli Federica, Vezzoli Valeria, Merlo Giorgio R, Cariboni Anna, Persani Luca, Gothilf Yoav, Bonomi Marco
Division of Endocrine and Metabolic Diseases & Lab. of Endocrine and Metabolic Research, IRCCS Istituto Auxologico Italiano, Milan, Italy -
Minerva Endocrinol. 2016 Jun;41(2):250-65. Epub 2016 Mar 2.
Gonadotropin-releasing hormone (GnRH) neurons have a pivotal role in the physiological functions of hypotahlamic-pituitary-gonadal (HPG) axis. The pulsatile releasing of GnRH hormone into the hypophyseal portal circulation at the median eminence represent the first domino in the HPG cascade of events that regulate the development, fertility and aging in all vertebrates. These neurons principally originate in the olfactory placode and migrate during early embryonal stages into the hypothalamus. Alterations in developmental processes or in the releasing of GnRH hormone lead to a rare and complex disorder of the reproductive axis called congenital hypogonadotropic hypogonadism (CHH). Genetic screening of human patients and the use of model systems have led to the identification of several genes involved in the CHH pathogenesis underlying its oligogenic nature. Nevertheless CHH remains, for a large cohort of patients, idiopathic and GnRH neurogenesis processes not fully understood. This is due to intrinsic difficulties that exist in the analysis of earliest embryonic developmental stages and in the methodologies developed to study the CHH-causing genes. In this regard, zebrafish embryos, on account of its external fertilization and development, allow a real-time analysis that could overcome some of the above mentioned limitations. Moreover, the recent availability of several transgenic zebrafish reporter lines makes it an excellent model for the study of the oligogenic mechanisms leading to CHH.
促性腺激素释放激素（GnRH）神经元在下丘脑 - 垂体 - 性腺（HPG）轴的生理功能中起关键作用。GnRH激素在正中隆起处脉冲式释放到垂体门脉循环中，这是调节所有脊椎动物发育、生育和衰老的HPG级联事件中的第一块多米诺骨牌。这些神经元主要起源于嗅基板，并在胚胎早期迁移到下丘脑。发育过程或GnRH激素释放的改变会导致一种罕见且复杂的生殖轴疾病，称为先天性低促性腺激素性性腺功能减退（CHH）。对人类患者进行基因筛查以及使用模型系统，已鉴定出几个与CHH发病机制相关的基因，其具有寡基因性质。然而，对于很大一部分患者来说，CHH仍然是特发性的，GnRH神经发生过程尚未完全了解。这是由于在分析最早的胚胎发育阶段以及研究导致CHH的基因所采用的方法中存在内在困难。在这方面，斑马鱼胚胎由于其体外受精和发育的特点，允许进行实时分析，从而可以克服上述一些限制。此外，最近有几种转基因斑马鱼报告系可供使用，这使其成为研究导致CHH的寡基因机制的优秀模型。
