Costa Marcia Helena Soares, Latronico Ana Claudia, Martin Regina Matsunaga, Barbosa Angela S, Almeida Madson Q, Lotfi Claudimara Ferini Pacicco, Valassi Helena P Lima, Nishi Mirian Yumie, Lucon Antonio Marmo, Siqueira Sheila Aparecida, Zerbini Maria Claudia Nogueira, Carvalho Luciani Renata, Mendonca Berenice Bilharinho, Fragoso Maria Candida Barisson Villares
Laboratório de Hormônios e Genética Molecular LIM/42, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, Avenue Dr Eneas de Carvalho Aguiar, São Paulo, SP, Brazil.
J Endocrinol. 2009 Feb;200(2):167-75. doi: 10.1677/JOE-08-0395. Epub 2008 Oct 29.
Glucose-dependent insulinotropic peptide receptor (GIPR) and LHCGR are G-protein-coupled receptors with a wide tissue expression pattern. Aberrant expression of these receptors has rarely been demonstrated in adult sporadic adrenocortical tumors with a lack of data on pediatric tumors. We quantified the GIPR and LHCGR expression in a large cohort of 55 patients (25 children and 30 adults) with functioning and non-functioning sporadic adrenocortical tumors. Thirty-eight tumors were classified as adenomas whereas 17 were carcinomas. GIPR and LHCGR expression were analyzed by real-time PCR and normal human pancreatic and testicular tissue samples were used as positive controls. Mean expression values were determined by fold increase in comparison with a normal adrenal pool. GIPR mRNA levels were significantly higher in adrenocortical carcinomas than in adenomas from both pediatric and adult groups. LHCGR expression was similar in both carcinomas and adenomas from the pediatric group but significantly lower in carcinomas than in adenomas from the adult group (median 0.06 and 2.3 respectively, P<0.001). GIPR was detected by immunohistochemistry in both pediatric and adult tumors. Staining and real-time PCR results correlated positively only when GIPR mRNA levels were increased at least two-fold in comparison with normal adrenal expression levels. In conclusion, GIPR overexpression was observed in pediatric and adult adrenocortical tumors and very low levels of LHCGR expression were found in all adult adrenocortical carcinomas.
葡萄糖依赖性促胰岛素多肽受体(GIPR)和促黄体生成素/绒毛膜促性腺激素受体(LHCGR)是具有广泛组织表达模式的G蛋白偶联受体。在成人散发性肾上腺皮质肿瘤中,这些受体的异常表达鲜有报道,关于儿童肿瘤的数据也很缺乏。我们对55例(25例儿童和30例成人)有功能和无功能的散发性肾上腺皮质肿瘤患者的队列进行了GIPR和LHCGR表达的定量分析。38个肿瘤被分类为腺瘤,17个为癌。通过实时聚合酶链反应(PCR)分析GIPR和LHCGR的表达,并使用正常人胰腺和睾丸组织样本作为阳性对照。通过与正常肾上腺样本相比的增加倍数来确定平均表达值。肾上腺皮质癌中GIPR信使核糖核酸(mRNA)水平显著高于儿童和成人组的腺瘤。儿童组的癌和腺瘤中LHCGR表达相似,但成人组中癌的LHCGR表达显著低于腺瘤(中位数分别为0.06和2.3,P<0.001)。通过免疫组织化学在儿童和成人肿瘤中均检测到GIPR。仅当GIPR mRNA水平与正常肾上腺表达水平相比增加至少两倍时,染色和实时PCR结果才呈正相关。总之,在儿童和成人肾上腺皮质肿瘤中均观察到GIPR过表达,并且在所有成人肾上腺皮质癌中均发现LHCGR表达水平极低。