Early multipotential pituitary focal hyperplasia in the α-subunit of glycoprotein hormone-driven pituitary tumor-transforming gene transgenic mice
Early multipotential pituitary focal hyperplasia in the α-subunit of glycoprotein hormone-driven pituitary tumor-transforming gene transgenic mice
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DOI：
10.1210/me.2004-0403
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发表时间：
2005-05-01
影响因子：
--
通讯作者：
Melmed, S
中科院分区：
文献类型：
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作者：
Abbud, RA;Takumi, I;Melmed, S
垂体肿瘤转化基因（PTTG）是从垂体肿瘤细胞系中分离的一种securin蛋白，在侵袭性肿瘤中高度表达，并表现出转化基因的特征。为了确定PTTG在垂体肿瘤发生中的作用，使用糖蛋白激素的α亚基将转基因人PTTG 1靶向小鼠垂体。雄性动物表现出多激素局灶性垂体转基因表达，伴有LH-、TSH-以及GH-细胞局灶性增生和腺瘤，与血清LH、GH、睾酮和/或IGF-I水平升高相关。MRI显示9 - 12个月时垂体和前列腺增大。前列腺增生和精囊增生引起的尿路梗阻，以及肾道炎症，导致一些动物在10个月内死亡。前列腺PTTG表达导致多激素增生和前列腺分泌微腺瘤，对前列腺和泌尿道具有显著的外周生长刺激作用。这些结果为早期垂体可塑性提供了证据，PTTG过表达导致早期垂体干细胞表型转换，并促进分化的多激素细胞灶性扩张。
Pituitary tumor-transforming gene (PTTG), a securin protein isolated from pituitary tumor cell lines, is highly expressed in invasive tumors and exhibits characteristics of a transforming gene. To determine the role of PTTG in pituitary tumorigenesis, transgenic human PTTG1 was targeted to the mouse pituitary using the alpha-subunit of glycoprotein hormone. Males showed plurihormonal focal pituitary transgene expression with LH-, TSH-, and, unexpectedly, also GH-cell focal hyperplasia and adenoma, associated with increased serum LH, GH, testosterone, and/or IGF-I levels. MRI revealed both pituitary and prostate enlargement at 9 - 12 months. Urinary obstruction caused by prostatic hyperplasia and seminal vesicle hyperplasia, with renal tract inflammation, resulted in death by 10 months in some animals. Pituitary PTTG expression results in plurihormonal hyperplasia and hormone-secreting microadenomas with profound peripheral growth-stimulatory effects on the prostate and urinary tract. These results provide evidence for early pituitary plasticity, whereby PTTG overexpression results in a phenotype switch in early pituitary stem cells and promotes differentiated polyhormonal cell focal expansion.