Glucagon-Like Peptide (GCGL) Is a Novel Potential TSH-Releasing Factor (TRF) in Chickens: I) Evidence for Its Potent and Specific Action on Stimulating TSH mRNA Expression and Secretion in the Pituitary
Glucagon-Like Peptide (GCGL) Is a Novel Potential TSH-Releasing Factor (TRF) in Chickens: I) Evidence for Its Potent and Specific Action on Stimulating TSH mRNA Expression and Secretion in the Pituitary
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胰高血糖素样肽 (GCGL) 是鸡中一种新型的潜在 TSH 释放因子 (TRF)：I) 其对刺激垂体中 TSH mRNA 表达和分泌的有效和特异性作用的证据。
DOI：
10.1210/en.2014-1331
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发表时间：
2014-11-01
期刊：
影响因子：
4.8
通讯作者：
Wang, Yajun
中科院分区：
文献类型：
--
作者：
Huang, Guian;He, Chen;Wang, Yajun
我们最近的研究提出，新的胰高血糖素样肽（GCGL），编码的胰高血糖素样基因在鸡和其他低等脊椎动物中发现，可能是一种垂体促生长因子在非哺乳类脊椎动物。为了验证这一假设，在这项研究中，我们研究了GCGL对鸡垂体的作用。结果表明：1）GCGL，而不是TRH，在体外孵育的完整垂体中或在通过蛋白质印迹或基于细胞的荧光素酶报告基因测定监测的培养的垂体细胞中有效且特异性地刺激TSH分泌; 2）GCGL通过定量实时RT-PCR检测，（0.1 nM-10 nM）剂量依赖性地诱导培养垂体细胞中TSHβ的mRNA表达，但不诱导其他5种激素基因的mRNA表达，可能由与GCGL受体（GCGLR）偶联的细胞内腺苷酸环化酶/cAMP/蛋白激酶A和磷脂酶C/肌醇1，4，5-三磷酸/Ca（2+）信号通路介导的作用;（3）原位杂交显示GCGLR mRNA主要定位于垂体头叶，即TSH细胞所在区域，进一步支持GCGL对促甲状腺细胞的直接作用。GCGL对垂体TSH表达和分泌的有效和特异性作用，以及GCGL在下丘脑和GCGLR和TSHβ在垂体中的时间表达谱之间显示的部分一致性，提供了下丘脑GCGL最有可能是鸡的一种新的TSH释放因子的第一个集体证据。这种新的潜在的促甲状腺激素释放因子（GCGL）的发现，在非哺乳类脊椎动物物种，即鸡，将有助于我们全面了解下丘脑控制的垂体-甲状腺轴的脊椎动物。
Our recent study proposed that the novel glucagon-like peptide (GCGL), encoded by a glucagon-like gene identified in chickens and other lower vertebrates, is likely a hypophysiotropic factor in nonmammalian vertebrates. To test this hypothesis, in this study, we investigated the GCGL action on chicken pituitaries. The results showed that: 1) GCGL, but not TRH, potently and specifically stimulates TSH secretion in intact pituitaries incubated in vitro or in cultured pituitary cells monitored by Western blotting or a cell-based luciferase reporter assay; 2) GCGL (0.1nM-10nM) dose dependently induces the mRNA expression of TSHβ but not 5 other hormone genes in cultured pituitary cells examined by quantitative real-time RT-PCR, an action likely mediated by intracellular adenylate cyclase/cAMP/protein kinase A and phospholipase C/inositol 1,4,5-trisphosphate/Ca(2+) signaling pathways coupled to GCGL receptor (GCGLR); 3) GCGLR mRNA is mainly localized in pituitary cephalic lobe demonstrated by in situ hybridization, where TSH-cells reside, further supporting a direct action of GCGL on thyrotrophs. The potent and specific action of GCGL on pituitary TSH expression and secretion, together with the partial accordance shown among the temporal expression profiles of GCGL in the hypothalamus and GCGLR and TSHβ in the pituitary, provides the first collective evidence that hypothalamic GCGL is most likely to be a novel TSH-releasing factor functioning in chickens. The discovery of this novel potential TSH-releasing factor (GCGL) in a nonmammalian vertebrate species, ie, chickens, would facilitate our comprehensive understanding of the hypothalamic control of pituitary-thyroid axis across vertebrates.