Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1524, 05508-900, São Paulo, SP, Brazil.
Mol Cell Endocrinol. 2010 Apr 12;317(1-2):1-7. doi: 10.1016/j.mce.2009.12.005. Epub 2009 Dec 14.
Cytoskeleton controls the stability of transcripts, by mechanisms that involve mRNAs and eEF1A attachment to it. Besides, it plays a key role in protein synthesis and secretion, which seems to be impaired in somatotrophs of hypothyroid rats, whose cytoskeleton is disarranged. This study investigated the: eEF1A and GH mRNA binding to cytoskeleton plus GH mRNA translation rate and GH secretion, in sham-operated and thyroidectomized rats treated with T3 or saline, and killed 30min thereafter. Thyroidectomy reduced: (a) pituitary F-actin content, and eEF1A plus GH mRNA binding to it; (b) GH mRNA recruitment to polysome; and (c) liver IGF-I mRNA expression, indicating that GH mRNA stability and translation rate, as well as GH secretion were impaired. T3 acutely reversed all these changes, which points toward a nongenomic action of T3 on cytoskeleton rearrangement, which might contribute to the increase on GH mRNA translation rate and GH secretion.
细胞骨架通过涉及 mRNAs 和 eEF1A 与其结合的机制来控制转录本的稳定性。此外，它在蛋白质合成和分泌中发挥着关键作用，而甲状腺功能减退症大鼠的生长激素（GH）细胞骨架排列紊乱，似乎会损害 GH 的合成和分泌，其生长激素细胞骨架排列紊乱。本研究探讨了：在甲状腺切除术大鼠和用 T3 或生理盐水处理的甲状腺切除术大鼠中，细胞骨架与 GH mRNA 结合、GH mRNA 翻译率和 GH 分泌，以及 30 分钟后处死的情况。甲状腺切除术降低了：（a）垂体 F-肌动蛋白含量，以及 eEF1A 和 GH mRNA 与其的结合；（b）GH mRNA 募集到多核糖体；以及（c）肝脏 IGF-I mRNA 的表达，表明 GH mRNA 的稳定性和翻译率以及 GH 分泌受损。T3 可迅速逆转所有这些变化，这表明 T3 对细胞骨架重排具有非基因组作用，这可能有助于增加 GH mRNA 的翻译率和 GH 分泌。
