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胃饥饿素在大鼠和人类甲状腺、甲状旁腺及其肿瘤中的定位。

Ghrelin localization in rat and human thyroid and parathyroid glands and tumours.

作者信息

Raghay Kawtar, García-Caballero Tomás, Nogueiras Rubén, Morel Gérard, Beiras Andrés, Diéguez Carlos, Gallego Rosalía

机构信息

Department of Morphological Sciences, University Clinical Hospital, University of Santiago de Compostela, c/S. Francisco, 15782 Santiago de Compostela, Spain.

出版信息

Histochem Cell Biol. 2006 Mar;125(3):239-46. doi: 10.1007/s00418-005-0044-6. Epub 2005 Sep 27.

DOI:10.1007/s00418-005-0044-6
PMID:16187069
Abstract

Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor (GHS-R), is a 28 amino acid peptide originally isolated from rat stomach that has been primarily involved in the central neuroregulation of GH secretion and food intake. Previous studies demonstrated that ghrelin has a widespread expression in different normal cells and tissues, as well as in gastric, thyroid, testicular, breast and lung neoplasias. In the current study, we use molecular biology to detect ghrelin transcripts expression in rats, and immunohistochemical techniques to investigate the cellular distribution of this peptide in rat and human thyroid and parathyroid glands and tumours. Ghrelin was localized in thyroid C cells and in parathyroid cells. Thyroid carcinomas (medullar, follicular and papillary) and parathyroid adenomas also showed intense and diffuse immunostaining for ghrelin. These data provide direct morphological evidence that ghrelin may well be acting in a paracrine fashion in the regulation of thyroid follicular cell function. The diffuse ghrelin immunostaining found in the parathyroid gland opens up the possibility of its secretion to the bloodstream or its involvement in the regulation of the parathyroid function. Overall, expression of ghrelin in human and rat thyroid and parathyroid glands is highly suggestive of a conserved role of this molecule in the regulation of thyroid and parathyroid cell function.

摘要

胃饥饿素是生长激素促分泌素受体(GHS-R)的内源性配体,是一种最初从大鼠胃中分离出的含28个氨基酸的肽,主要参与生长激素分泌和食物摄入的中枢神经调节。先前的研究表明,胃饥饿素在不同的正常细胞和组织以及胃癌、甲状腺癌、睾丸癌、乳腺癌和肺癌中广泛表达。在本研究中,我们使用分子生物学方法检测大鼠胃饥饿素转录本的表达,并采用免疫组织化学技术研究该肽在大鼠和人类甲状腺及甲状旁腺及其肿瘤中的细胞分布。胃饥饿素定位于甲状腺C细胞和甲状旁腺细胞中。甲状腺癌(髓样癌、滤泡癌和乳头状癌)和甲状旁腺腺瘤也显示出对胃饥饿素强烈且弥漫的免疫染色。这些数据提供了直接的形态学证据,表明胃饥饿素很可能以旁分泌方式调节甲状腺滤泡细胞功能。在甲状旁腺中发现的弥漫性胃饥饿素免疫染色表明其可能分泌入血液或参与甲状旁腺功能的调节。总体而言,胃饥饿素在人和大鼠甲状腺及甲状旁腺中的表达强烈提示该分子在调节甲状腺和甲状旁腺细胞功能方面具有保守作用。

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本文引用的文献

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Identification of promoter region of ghrelin gene in human medullary thyroid carcinoma cell line.人甲状腺髓样癌细胞系中胃饥饿素基因启动子区域的鉴定
Life Sci. 2004 Sep 17;75(18):2193-201. doi: 10.1016/j.lfs.2004.04.028.
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Ghrelin exerts a proliferative effect on a rat pituitary somatotroph cell line via the mitogen-activated protein kinase pathway.胃饥饿素通过丝裂原活化蛋白激酶途径对大鼠垂体生长激素细胞系发挥增殖作用。
Eur J Endocrinol. 2004 Aug;151(2):233-40. doi: 10.1530/eje.0.1510233.
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Cellular distribution and regulation of ghrelin messenger ribonucleic acid in the rat pituitary gland.
胃饥饿素的保护和治疗作用及其对消化系统癌症的风险。
Int J Mol Sci. 2021 Sep 29;22(19):10571. doi: 10.3390/ijms221910571.
4
Ghrelin-O-Acyltransferase (GOAT) Enzyme as a Novel Potential Biomarker in Gastroenteropancreatic Neuroendocrine Tumors.胃饥饿素-O-酰基转移酶(GOAT)酶作为胃肠胰神经内分泌肿瘤的一种新的潜在生物标志物。
Clin Transl Gastroenterol. 2018 Oct 8;9(10):196. doi: 10.1038/s41424-018-0058-8.
5
Serum ghrelin levels in papillary thyroid carcinoma.甲状腺乳头状癌患者的血清胃饥饿素水平
Arch Endocrinol Metab. 2017 Sept-Oct;61(5):464-469. doi: 10.1590/2359-3997000000290. Epub 2017 Sep 18.
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Adipocytokines in thyroid dysfunction.甲状腺功能障碍中的脂肪细胞因子。
ISRN Inflamm. 2013 Jun 23;2013:646271. doi: 10.1155/2013/646271.
7
The use of ghrelin and ghrelin receptor agonists as a treatment for animal models of disease: efficacy and mechanism.生长激素释放肽及生长激素释放肽受体激动剂治疗疾病动物模型的作用:疗效和机制。
Curr Pharm Des. 2012;18(31):4779-99. doi: 10.2174/138161212803216951.
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Current and potential roles of ghrelin in clinical practice.生长激素释放肽在临床实践中的当前和潜在作用。
J Endocrinol Invest. 2010 Dec;33(11):823-38. doi: 10.1007/BF03350350.
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Functional expression of the thyrotropin receptor in C cells: new insights into their involvement in the hypothalamic-pituitary-thyroid axis.C 细胞中促甲状腺激素受体的功能表达:对其参与下丘脑-垂体-甲状腺轴的新认识。
J Anat. 2009 Aug;215(2):150-8. doi: 10.1111/j.1469-7580.2009.01095.x. Epub 2009 Jun 1.
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C cells evolve at the same rhythm as follicular cells when thyroidal status changes in rats.当大鼠甲状腺状态发生变化时,C 细胞的演变与滤泡细胞的演变同步。
J Anat. 2009 Mar;214(3):301-9. doi: 10.1111/j.1469-7580.2008.01044.x.
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4
Ghrelin promotes pancreatic adenocarcinoma cellular proliferation and invasiveness.胃饥饿素促进胰腺癌细胞增殖和侵袭。
Biochem Biophys Res Commun. 2003 Sep 19;309(2):464-8. doi: 10.1016/j.bbrc.2003.08.024.
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Expression of ghrelin in the cyclic and pregnant rat ovary.胃饥饿素在周期性和妊娠大鼠卵巢中的表达。
Endocrinology. 2003 Apr;144(4):1594-602. doi: 10.1210/en.2002-221058.
6
Ontogeny and tissue-specific regulation of ghrelin mRNA expression suggest that ghrelin is primarily involved in the control of extraendocrine functions in the rat.胃饥饿素mRNA表达的个体发生及组织特异性调控表明,胃饥饿素主要参与大鼠内分泌外功能的控制。
Neuroendocrinology. 2003 Feb;77(2):91-9. doi: 10.1159/000068653.
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The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis.胃饥饿素在中枢神经系统中的分布及作用机制表明存在一条调节能量平衡的新型下丘脑回路。
Neuron. 2003 Feb 20;37(4):649-61. doi: 10.1016/s0896-6273(03)00063-1.
8
Ghrelin and growth hormone secretagogue receptor are expressed in the rat adrenal cortex: Evidence that ghrelin stimulates the growth, but not the secretory activity of adrenal cells.胃饥饿素和生长激素促分泌素受体在大鼠肾上腺皮质中表达:胃饥饿素刺激肾上腺细胞生长但不刺激其分泌活性的证据。
FEBS Lett. 2003 Feb 11;536(1-3):173-9. doi: 10.1016/s0014-5793(03)00051-6.
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Immunolocalization of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in the cyclic human ovary.胃饥饿素及其功能性受体1a型生长激素促分泌素受体在周期性人类卵巢中的免疫定位。
J Clin Endocrinol Metab. 2003 Feb;88(2):879-87. doi: 10.1210/jc.2002-021196.
10
Hyperthyroidism is associated with suppressed circulating ghrelin levels.甲状腺功能亢进与循环中胃饥饿素水平受抑制有关。
J Clin Endocrinol Metab. 2003 Feb;88(2):853-7. doi: 10.1210/jc.2002-021302.