Heritable disorders of pituitary development.
Heritable disorders of pituitary development.
复制标题
DOI：
10.1210/jcem.84.12.6209
复制
发表时间：
1999-12
期刊：
影响因子：
--
通讯作者：
John S. Parks;Milton R. Brown;D. Hurley;C. Phelps;M. Wajnrajch
中科院分区：
文献类型：
--
作者：
John S. Parks;Milton R. Brown;D. Hurley;C. Phelps;M. Wajnrajch
在过去的20年里，基础和转化研究的成果已经揭示了几种遗传形式的垂体功能减退症的分子机制。仅限于下丘脑、垂体、GH轴的疾病是由该轴的单个组分突变引起的。涉及GH和一种或多种其他垂体激素的疾病是由指导垂体前叶胚胎发育的同源结构域转录因子突变引起的。Pit-1具有POU特异性和POU同源DNA结合结构域。PIT 1基因突变产生的表型涉及GH、PRL和TSH的缺乏。前列腺要么很小，要么大小正常。PROP 1基因编码具有单个配对样DNA结合结构域的转录因子。PROP 1失活突变的人缺乏LH和FSH，以及GH，PRL和TSH。他们的垂体腺可能很小，大小正常，也可能非常大，并显示鞍上延伸。垂体变性可导致获得性ACTH缺乏。HESX 1基因的表达先于PROP 1和PIT 1的表达，并且其更为广泛。该蛋白质具有配对样结构域，并且它与PROP 1的产物竞争DNA结合。HESX 1失活突变的纯合性产生类似于视隔发育不良的复杂表型。关于HESX 1突变在其他形式的垂体功能减退症中的作用，还需要了解更多。
Basic and translational research achievements over the past 2 decades have disclosed the molecular mechanisms underlying several genetic forms of hypopituitarism. Disorders that are limited to the hypothalamic, pituitary, GH axis are caused by mutations in individual components of that axis. Disorders involving GH and one or more additional pituitary hormones are caused by mutations in the homeodomain transcription factors that direct embryological development of the anterior pituitary gland. Pit-1 has a POU-specific and a POU-homeo DNA-binding domain. The phenotype produced by mutations in the PIT1 gene involves deficiencies of GH, PRL, and TSH. Pituitary glands are either small or normally sized. The PROP1 gene encodes a transcription factor with a single paired-like DNA-binding domain. Persons with inactivating mutations in PROP1 have deficiencies of LH and FSH, as well as GH, PRL, and TSH. Their pituitary glands may be small, normally sized, or extremely large and show suprasellar extension. Pituitary degeneration may produce acquired deficiency of ACTH. Expression of the HESX1 gene precedes expression of PROP1 and PIT1, and it is much more widespread. The protein has a paired-like domain, and it competes with the product of PROP1 for DNA-binding. Homozygosity for inactivating mutations of HESX1 produces a complex phenotype that resembles septo-optic dysplasia. Much more needs to be learned about the role of HESX1 mutations in other forms of hypopituitarism.