Gsh-1, an orphan Hox gene, is required for normal pituitary development
Gsh-1, an orphan Hox gene, is required for normal pituitary development
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DOI：
10.1002/j.1460-2075.1996.tb00407.x
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发表时间：
1996-02-15
期刊：
影响因子：
11.4
通讯作者：
Potter, SS
中科院分区：
文献类型：
--
作者：
Li, H;Zeitler, PS;Potter, SS
垂体前叶调节多个器官系统的功能以及身体的生长，并反过来由下丘脑释放的肽控制。我们发现，GSH-1同源盒基因突变的结果在多效性垂体发育和功能的影响。纯合子突变体表现出极端侏儒症，性发育不良和显着的围产期死亡率。突变的垂体体积小，细胞减少，生长激素和催乳素产生细胞的数量严重减少。此外，垂体激素的一个子集的垂体含量，包括生长激素，催乳素和黄体生成素，显着减少。下丘脑虽然形态正常，但在突变体中也受到干扰。Gsh-1基因是下丘脑弓状核生长激素释放激素（GHRH）基因表达所必需的。此外，序列和电泳迁移率变化数据表明，GSH-1和GHRH基因作为潜在的目标调节的GSH-1编码的蛋白质。突变表型表明GSH-1在下丘脑-垂体轴的形成和功能的遗传层次中起着关键作用。
The anterior pituitary regulates the function of multiple organ systems as well as body growth, and in turn is controlled by peptides released by the hypothalamus. We find that mutation of the Gsh-1 homeobox gene results in pleiotropic effects on pituitary development and function. Homozygous mutants exhibit extreme dwarfism, sexual infantilism and significant perinatal mortality. The mutant pituitary is small in size and hypocellular, with severely reduced numbers of growth hormone- and prolactin-producing cells. Moreover, the pituitary content of a subset of pituitary hormones, including growth hormone, prolactin and luteinizing hormone, is significantly decreased. The hypothalamus, although morphologically normal, is also perturbed in mutants. The Gsh-1 gene is shown to be essential for growth hormone-releasing hormone (GHRH) gene expression in the arcuate nucleus of the hypothalamus. Further, sequence and electrophoretic mobility shift data suggest the Gsh-1 and GHRH genes as potential targets regulated by the Gsh-1-encoded protein. The mutant phenotype indicates a critical role for Gsh-1 in the genetic hierarchy of the formation and function of the hypothalamic-pituitary axis.