Volante Marco, Allia Elena, Fulcheri Ezio, Cassoni Paola, Ghigo Ezio, Muccioli Giampiero, Papotti Mauro
Departments of Pathology, Endocrinology, and Pharmacology, University of Turin, Turin.
Am J Pathol. 2003 Feb;162(2):645-54. doi: 10.1016/S0002-9440(10)63858-8.
Ghrelin, a growth hormone-releasing hormone produced by gastroenteropancreatic endocrine cells, hypothalamus, and pituitary, was recently identified in medullary thyroid carcinomas and derived cell lines. However, no data exist on its expression in either normal or neoplastic thyroid follicular cells. We analyzed ghrelin expression by immunohistochemistry, in situ hybridization, and reverse transcriptase-polymerase chain reaction in 15 fetal, 4 infant, and 10 adult thyroids, and in 54 tumors of follicular origin. We also analyzed the effects of ghrelin on cell proliferation in N-PAP and ARO thyroid carcinoma cell lines. Ghrelin-binding sites were investigated using reverse transcriptase-polymerase chain reaction to detect its growth hormone secretagogue receptor (GHS-R) mRNA and an in situ-binding localization procedure. Strong ghrelin immunoreactivity was found in fetal but not in infant or adult thyroids. Ghrelin protein and mRNA were present, in variable amounts, in benign and malignant tumors. Normal thyroids, thyroid tumors, and cell lines showed ghrelin binding sites by binding localization, in the absence of the specific GHS receptor mRNA (with the exception of one normal thyroid). Moreover, ghrelin induced dose-dependent inhibition of growth in cell lines. In conclusion, ghrelin is expressed in fetal but not in adult thyroid, and is re-expressed in tumors; the presence of ghrelin receptors other than GHS-R in normal and neoplastic adult thyroid is suggested; ghrelin inhibits cell proliferation of thyroid carcinoma cell lines in vitro.
胃泌素释放肽是一种由胃肠胰内分泌细胞、下丘脑和垂体产生的生长激素释放激素，最近在甲状腺髓样癌及其衍生细胞系中被发现。然而，关于其在正常或肿瘤性甲状腺滤泡细胞中的表达尚无数据。我们通过免疫组织化学、原位杂交和逆转录聚合酶链反应分析了15例胎儿、4例婴儿和10例成人甲状腺以及54例滤泡源性肿瘤中胃泌素释放肽的表达。我们还分析了胃泌素释放肽对N-PAP和ARO甲状腺癌细胞系细胞增殖的影响。使用逆转录聚合酶链反应检测其生长激素促分泌素受体（GHS-R）mRNA，并采用原位结合定位程序研究胃泌素释放肽结合位点。在胎儿甲状腺中发现了强烈的胃泌素释放肽免疫反应性，而在婴儿或成人甲状腺中未发现。在良性和恶性肿瘤中均存在不同量的胃泌素释放肽蛋白和mRNA。正常甲状腺、甲状腺肿瘤和细胞系通过结合定位显示胃泌素释放肽结合位点，但未检测到特异性GHS受体mRNA（有一个正常甲状腺除外）。此外，胃泌素释放肽可诱导细胞系生长的剂量依赖性抑制。总之，胃泌素释放肽在胎儿甲状腺中表达，而在成人甲状腺中不表达，在肿瘤中重新表达；提示在正常和肿瘤性成人甲状腺中存在除GHS-R以外的胃泌素释放肽受体；胃泌素释放肽在体外可抑制甲状腺癌细胞系的细胞增殖。
