Scopa C D, Mastorakos G, Friedman T C, Melachrinou M, Merino M J, Chrousos G P
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Am J Pathol. 1994 Nov;145(5):1159-67.
Corticotropin-releasing hormone (CRH) functions as a regulator of the hypothalamic-pituitary-adrenal axis and coordinator of the stress response. Immunoreactive CRH (IrCRH) is also produced in a variety of inflammatory sites, where this peptide acts as a proinflammatory cytokine. To detect CRH in autoimmune thyroid disease as well as in disorders that may be associated with an inflammatory reaction within this gland, we examined immunohistochemically 45 thyroid lesions, including 12 nodular goiters, 9 cases of Hashimoto thyroiditis, 6 follicular adenomas, 4 follicular and 8 papillary carcinomas, 4 Hürthle cell tumors, 1 medullary cancer, and 1 insular thyroid carcinoma. We also examined the presence of IrCRH in the adjacent normal thyroid parenchyma. The avidin-biotin complex method was employed on formalin-fixed, paraffin-embedded tissue, using a highly specific, affinity-purified polyclonal rabbit anti-CRH antibody. Granular cytoplasmic immunostaining of follicular cells was observed in 100% of the cases of Hashimoto thyroiditis, 77% of the neoplasms and 42% of goiters. The intensity of the staining was more pronounced in Hashimoto thyroiditis and Hürthle cell tumors, whereas the remaining lesions exhibited a heterogeneous staining pattern. No IrCRH was observed in the normal thyroid parenchyma. Using a specific radioimmunoassay, the IrCRH in extracts of simple thyroid goiters, papillary carcinomas, and Hürthle cell tumors ranged between 0.031 and 0.224 pmol/g of wet tissue but was undetectable in normal thyroid parenchyma. The IrCRH molecule in the thyroid gland eluted at the same fraction as synthetic rat/human CRH 1-41 in reverse phase high pressure liquid chromatography. We conclude that IrCRH is present in thyroid lesions, predominantly in those related to autoimmune phenomena, suggesting that this neuropeptide may be directly and/or indirectly involved with inflammatory processes taking place in this gland.
促肾上腺皮质激素释放激素(CRH)作为下丘脑 - 垂体 - 肾上腺轴的调节因子和应激反应的协调者发挥作用。免疫反应性CRH(IrCRH)也在多种炎症部位产生,在这些部位该肽作为促炎细胞因子发挥作用。为了检测自身免疫性甲状腺疾病以及可能与此腺体炎症反应相关的疾病中的CRH,我们对45个甲状腺病变进行了免疫组织化学检查,包括12例结节性甲状腺肿、9例桥本甲状腺炎、6例滤泡性腺瘤、4例滤泡癌和8例乳头状癌、4例许特莱细胞肿瘤、1例髓样癌和1例岛状甲状腺癌。我们还检查了相邻正常甲状腺实质中IrCRH的存在情况。采用抗生物素蛋白 - 生物素复合物法对福尔马林固定、石蜡包埋的组织进行检测,使用高度特异性、亲和纯化的兔抗CRH多克隆抗体。在100%的桥本甲状腺炎病例、77%的肿瘤和42%的甲状腺肿病例中观察到滤泡细胞的颗粒状细胞质免疫染色。染色强度在桥本甲状腺炎和许特莱细胞肿瘤中更为明显,而其余病变表现出异质性染色模式。在正常甲状腺实质中未观察到IrCRH。使用特异性放射免疫测定法,单纯性甲状腺肿、乳头状癌和许特莱细胞肿瘤提取物中的IrCRH含量在0.031至0.224 pmol/g湿组织之间,但在正常甲状腺实质中未检测到。在反相高压液相色谱中,甲状腺中的IrCRH分子与合成大鼠/人CRH 1 - 41在相同馏分中洗脱。我们得出结论,IrCRH存在于甲状腺病变中,主要存在于与自身免疫现象相关的病变中,表明这种神经肽可能直接和/或间接参与该腺体发生的炎症过程。