de Roux Nicolas, Carel Jean-Claude, Léger Juliane
Endocr Dev. 2016;29:72-86. doi: 10.1159/000438875. Epub 2015 Dec 17.
Reproductive function depends on the activity of the gonadotropic axis, which is controlled by a hypothalamic neural network whose main function is to regulate the secretion of gonadotropin-releasing hormone (GnRH). This endocrine network is not mature at birth, and several phases of activation-inactivation of the gonadotropic axis are necessary for its normal development. The postnatal maturation of the GnRH network lies under the control of a neurodevelopmental program that starts in fetal life and ends at puberty. There are many clinical situations in which this program is interrupted, leading to congenital hypogonadotropic hypogonadism (CHH) and an absence of puberty. For many years, attention has mainly been focused on the genetics of isolated CHH. More recently, the emergence of new genomics techniques has led to the description of genetic defects in very rare syndromes in which CHH is associated with complex neurological dysfunctions. Here, we review the clinical phenotype and genetic defects linked to such syndromic CHH. This analysis highlights the close link between the ubiquitin pathway, synaptic proteins and CHH, as well as unexpected mutations in genes encoding nucleolar proteins.
生殖功能取决于促性腺轴的活性，促性腺轴由下丘脑神经网络控制，该神经网络的主要功能是调节促性腺激素释放激素（GnRH）的分泌。这种内分泌网络在出生时并不成熟，促性腺轴的几个激活-失活阶段对其正常发育是必要的。GnRH网络的产后成熟受神经发育程序的控制，该程序始于胎儿期，结束于青春期。在许多临床情况下，这个程序会被中断，导致先天性低促性腺激素性性腺功能减退（CHH）和青春期缺失。多年来，注意力主要集中在孤立性CHH的遗传学上。最近，新的基因组学技术的出现导致了对非常罕见综合征中遗传缺陷的描述，在这些综合征中，CHH与复杂的神经功能障碍有关。在这里，我们综述了与这种综合征性CHH相关的临床表型和遗传缺陷。该分析突出了泛素途径、突触蛋白与CHH之间的密切联系，以及编码核仁蛋白基因中的意外突变。
