Human GnRH Deficiency: A Unique Disease Model to Unravel the Ontogeny of GnRH Neurons
Human GnRH Deficiency: A Unique Disease Model to Unravel the Ontogeny of GnRH Neurons
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DOI：
10.1159/000314193
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发表时间：
2010-01-01
影响因子：
4.1
通讯作者：
Crowley, William F., Jr.
中科院分区：
文献类型：
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作者：
Balasubramanian, Ravikumar;Dwyer, Andrew;Crowley, William F., Jr.
一个物种的进化生存在很大程度上是其繁殖适应性的函数。在哺乳动物中，一个分布稀疏且广泛分散的下丘脑神经元网络，即促性腺激素释放激素（GnRH）神经元，通过GnRH的协同分泌充当繁殖的指示灯。自从首次被描述以来，人类GnRH缺乏症在临床和遗传学上都被认为是一种异质性疾病。已经描述了一系列不同的生殖表型，包括伴有嗅觉缺失的先天性GnRH缺乏症（卡尔曼综合征）、伴有正常嗅觉的先天性GnRH缺乏症（嗅觉正常的特发性低促性腺激素性性腺功能减退症）以及成年发病的低促性腺激素性性腺功能减退症。在过去的二十年中，通过对GnRH缺乏症患者的研究，已经发现了几个控制GnRH个体发育的基因和途径。更重要的是，对这些患者的详细研究突出了寡基因性和基因型协同作用这一新兴主题，并且随着一些患者在成年后期GnRH缺乏症逆转的记录，也扩大了表型多样性。潜在的基因缺陷也有助于理解在这些患者中的一些人身上看到的相关非生殖表型。这些见解现在为临床医生提供了有针对性的基因诊断策略，并且对临床管理产生影响。版权所有 (C) 2010 S. Karger AG，巴塞尔
Evolutionary survival of a species is largely a function of its reproductive fitness. In mammals, a sparsely populated and widely dispersed network of hypothalamic neurons, the gonadotropin-releasing hormone (GnRH) neurons, serve as the pilot light of reproduction via coordinated secretion of GnRH. Since it first description, human GnRH deficiency has been recognized both clinically and genetically as a heterogeneous disease. A spectrum of different reproductive phenotypes comprised of congenital GnRH deficiency with anosmia (Kallmann syndrome), congenital GnRH deficiency with normal olfaction (normosmic idiopathic hypogonadotropic hypogonadism), and adult-onset hypogonadotropic hypogonadism has been described. In the last two decades, several genes and pathways which govern GnRH ontogeny have been discovered by studying humans with GnRH deficiency. More importantly, detailed study of these patients has highlighted the emerging theme of oligogenicity and genotypic synergism, and also expanded the phenotypic diversity with the documentation of reversal of GnRH deficiency later in adulthood in some patients. The underlying genetic defect has also helped understand the associated nonreproductive phenotypes seen in some of these patients. These insights now provide practicing clinicians with targeted genetic diagnostic strategies and also impact on clinical management. Copyright (C) 2010 S. Karger AG, Basel