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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The double-stranded RNA-binding protein, PACT, is required for postnatal anterior pituitary proliferation
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The double-stranded RNA-binding protein, PACT, is required for postnatal anterior pituitary proliferation

机译：产后垂体前叶增殖需要双链RNA结合蛋白PACT

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摘要

PACT is a double-stranded RNA-binding protein that also binds and activates the latent protein kinase, PKR, which plays a major role in cellular antiviral defense in mammals. For evaluating PACT'S contribution to the innate immune system, Pact~(-/-) mice have been generated; these mice exhibit notable developmental abnormalities including microtia, with craniofacial, ear, and hearing defects. Here we report that, in addition. Pact~(-/-) mice had smaller body size and fertility defects, both of which were caused by defective pituitary functions. Pact~(-/-) mice exhibited anterior pituitary lobe (AL) hypoplasia, which developed postnatally, when the second phase of pituitary expansion occurs. Among the 5 cell types in AL, the numbers of corticotrophs, gonadotrophs, and somatotrophs were equally decreased in Pact~(-/-) mice with a greater impact on lactotrophs and a lesser impact on thyrotrophs. PACT mRNA and protein were highly expressed in the pituitary of wild-type (Wt) mice during the postnatal wave of AL proliferation, the same period in which the hypoplasia developed in Pact mice. During this time, the pituitaries of Pact~(-/-) mice did not exhibit significantly increased apoptosis compared with Wt mice but showed a decrease in cell proliferation. The inhibition of cell proliferation observed in vivo could be recapitulated in vitro in GH3 somato/ lactotroph and LβT2 gonadotroph cell lines; knockdown of PACT expression with siRNA diminished the rate of proliferation of these cells. Our study revealed a physiologically significant role for PACT in cell proliferation and an essential role of a dsRNA-binding protein in mammalian pituitary expansion.
机译：PACT是一种双链RNA结合蛋白，还可以结合并激活潜在的蛋白激酶PKR，该蛋白激酶在哺乳动物细胞的抗病毒防御中起着重要作用。为了评估PACT对先天免疫系统的贡献，已经产生了Pact _（-/-）小鼠。这些小鼠表现出显着的发育异常，包括小口畸形，颅面，耳和听力缺陷。另外，我们在此报告。 Pact〜（-/-）小鼠的体型和生育能力缺陷较小，两者都是由垂体功能缺陷引起的。 Pact〜（-/-）小鼠表现出垂体前叶（AL）发育不全，当垂体扩张的第二阶段发生时，它在出生后发展。在AL的5种细胞类型中，Pact〜（-/-）小鼠的皮质营养型，促性腺营养型和体营养型的数量平均减少，对乳酸营养型的影响更大，对甲状腺营养型的影响较小。 PACT mRNA和蛋白在出生后的AL增生波中在野生型（Wt）小鼠的脑垂体中高表达，而在Pact小鼠发育不全的同一时期。在此期间，与Wt小鼠相比，Pact〜（-/-）小鼠的垂体并没有表现出明显的凋亡增加，但细胞增殖却降低了。体内观察到的对细胞增殖的抑制作用可以在GH3体细胞/泌乳营养细胞和LβT2促性腺激素细胞系中进行体外概括。 siRNA抑制PACT表达可减少这些细胞的增殖速率。我们的研究揭示了PACT在细胞增殖中的生理重要作用，以及dsRNA结合蛋白在哺乳动物垂体扩张中的重要作用。

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  • 作者

    Gregory A. Peters; Darcie D. Seachrist; Ruth A. Keri; Ganes C. Sen;

  • 作者单位

    Department of Molecular Genetics, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195;

    Department of Pharmacology and Division of General Medical Sciences-Oncology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106;

    Department of Pharmacology and Division of General Medical Sciences-Oncology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106;

    Department of Molecular Genetics, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    adenohypophysis; development; fertility; hypoplasia; pituitary expansion;

    机译：腺垂体;发展生育能力发育不全;垂体扩张;

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