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首页> 外文期刊>Endocrinology >Runt-related transcription factors impair activin induction of the follicle-stimulating hormone {beta}-subunit gene.
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Runt-related transcription factors impair activin induction of the follicle-stimulating hormone {beta}-subunit gene.

机译：矮子相关的转录因子会损害促卵泡激素β-亚基基因的激活素诱导。

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摘要

Synthesis of the FSH beta-subunit (FSHbeta) is critical for normal reproduction in mammals, and its expression within the pituitary gonadotrope is tightly regulated by activin. Here we show that Runt-related (RUNX) proteins, transcriptional regulators known to interact with TGFbeta signaling pathways, suppress activin induction of FSHbeta gene expression. Runx2 is expressed within the murine pituitary gland and dramatically represses activin-induced FSHbeta promoter activity, without affecting basal expression in LbetaT2 cells, an immortalized mouse gonadotrope cell line. This repressive effect is specific, because RUNX2 induces LHbeta transcription (with or without activin) and does not interfere with GnRH induction of either gonadotropin beta-subunit gene. Analysis of the murine FSHbeta promoter by transfection and gel shift assays reveals that RUNX2 repression localizes to a Runx-binding element at -159/-153, which is adjacent to a previously recognized region critical for activin induction. Mutation of this -153 activin-response element or, indeed, any of the five activin-responsive regions prevents activin induction and, in fact, RUNX2 suppression, instead converting RUNX2 to an activator of the FSHbeta gene. Although the Runx-binding element is required for RUNX2-mediated repression of FSHbeta induction by either activin or Smad3, confirming a functional role of this novel site, protein interactions in addition to those between RUNX2 and Smads are necessary to account for full repression of activin induction. In summary, the present study provides evidence for Runx2-mediated repression of activin-induced FSHbeta gene expression and reveals the context dependence of Runx2 action in hormonal regulation of the gonadotropin genes.
机译：FSHβ亚基（FSHbeta）的合成对于哺乳动物的正常繁殖至关重要，其在垂体促性腺激素中的表达受到激活素的严格调节。在这里，我们显示Runt相关（RUNX）蛋白，已知与TGFbeta信号通路相互作用的转录调节因子，抑制FSHbeta基因表达的激活素诱导。 Runx2在鼠脑垂体中表达，并显着抑制激活素诱导的FSHbeta启动子活性，而不会影响永生化的小鼠性腺型生殖细胞LbetaT2细胞的基础表达。这种抑制作用是特异性的，因为RUNX2诱导LHbeta转录（带有或不带有激活素），并且不干扰任何促性腺激素β亚基基因的GnRH诱导。通过转染和凝胶迁移分析对鼠类FSHbeta启动子的分析表明，RUNX2阻遏作用位于-159 / -153处的Runx结合元件上，该元件与先前公认的激活素诱导关键区域相邻。此-153激活素响应元件或五个激活素响应区域中任何一个的突变，都可以防止激活素诱导，实际上是RUNX2抑制，而不是将RUNX2转换为FSHbeta基因的激活剂。尽管Runx结合元件是激活素或Smad3介导的RUNX2介导的FSHbeta诱导阻遏所必需的，这证实了这一新位点的功能作用，但RUNX2和Smads之间的相互作用之外的蛋白质相互作用对于解释激活素的完全抑制是必需的。感应。总之，本研究为Runx2介导的激活素诱导的FSHbeta基因表达的抑制提供了证据，并揭示了Runx2作用在促性腺激素基因激素调节中的背景依赖性。

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