Development of laboratory testing methods through isolation of pituitary specific genes.

通过分离垂体特定基因开发实验室测试方法。

• 批准号: 13672422
• 负责人: TATSUMI Keita
• 金额: $ 1.98万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672422/
• 关键词: pituitary; lymphocytic hypophysitis; autoantibodies; PGSF1a; PGSF1; PGSF2; GH; Body Map; 遺伝子

To isolate novel transcripts expressed specifically in this gland, identified three novel pituitary-specific transcripts which encode putative proteins: pituitary gland specific factor 1a (PGSF1a), PGSF1b and PGSF2 through generating pituitary BodyMap database. To understand the pathogenesis of lymphocytic hypophysitis and to diagnose this disease efficiently, we developed laboratory testing methods. By developing radioligand assay using recombinant human 35S-labeled protein, presence of autoantibodies against three pituitary-specific proteins, GH, PGSF1a and PGSF2, and 5 enzymes expressed in the pituitary gland, prohormone convertase (PC) 1/3, PC2, carboxypeptidase E (CPE), alpha enolase, and PC2 regulatory protein, 7B2 were analyzed. Anti-human GH, anti-PGSF1a, and anti-PGSF2 antibodies (Ab) were detected in patients with lymphocytic hypophysitis and other hypopituitarism, but were not detected in patients with non-functioning pituitary macroadenoma. Patients positive for either anti-PC1/3 or anti-7B2 Ab were significantly frequent among patients with nonfunctioning pituitary macroadenoma than in other pituitary diseases and healthy controls. None of the patients was positive for anti-PC2 Ab or anti-CPE Ab. Anti-alpha-enolase Ab were not suitable for specific diagnosis of lymphocytic hypophysitis or pituitary non-functioning adenoma. Detection of antibodies against GH, PGSF1a, PGSF2, PC1/3 and 7B2 may be useful for the diagnosis of lymphocytic hypophysitis.

为了分离垂体特异表达的新转录本，通过构建垂体BodyMap数据库，鉴定了3个垂体特异性转录本：垂体特异性因子1a（pituitary gland specific factor 1a，PGSF 1b）和PGSF 2。为了了解淋巴细胞性垂体炎的发病机制，并有效地诊断这种疾病，我们开发了实验室检测方法。通过使用重组人35 S标记蛋白开发放射性配体测定法，分析了针对三种垂体特异性蛋白GH、PGSF 1a和PGSF 2以及在垂体中表达的5种酶激素原转化酶（PC）1/3、PC 2、羧肽酶E（CPE）、α烯醇化酶和PC 2调节蛋白7 B2的自身抗体的存在。在淋巴细胞性垂体炎和其他垂体功能减退症患者中检测到抗人GH、抗PGSF 1a和抗PGSF 2抗体（Ab），但在无功能垂体大腺瘤患者中未检测到。无功能性垂体大腺瘤患者抗PC 1/3或抗7 B2抗体阳性率显著高于其他垂体疾病和健康对照者。所有患者抗PC 2抗体和抗CPE抗体均为阴性。抗α-烯醇化酶抗体不适合淋巴细胞性垂体炎或垂体无功能性腺瘤的特异性诊断。GH、PGSF 1a、PGSF 2、PC 1/3和7 B2抗体的检测对淋巴细胞性垂体炎的诊断有一定价值。

项目成果

Tanaka S: "Detection of autoantibodies against the pituitary-specific proteins in patients with lymphocytic hypophysitis"Eur J Endocrinol. 147,6. 767-775 (2002)

Tanaka S：“淋巴细胞性垂体炎患者垂体特异性蛋白自身抗体的检测”Eur J Endocrinol。

Izumi Y: "Development of liver dysfunction after delivery is possibly due to postpartum autoimmune hepatitis. A report of three cases"J Intern Med. 252,4. 361-367 (2002)

Izumi Y：“产后出现肝功能障碍可能是由于产后自身免疫性肝炎。三例报告”J Intern Med。

Tatsumi K, Tanaka S, Takano T, Tahara S, Murakami Y, Takao T, Hashimoto K, Kato Y, Teramoto A, Amino N: "Frequent appearance of autoantibodies against prohormone convertase 1/3 and neuroendocrine protein 7B2 in patients with non-functioning pituitary macr

Tatsumi K、Tanaka S、Takano T、Tahara S、Murakami Y、Takao T、Hashimoto K、Kato Y、Teramoto A、Amino N：“非激素原转化酶 1/3 和神经内分泌蛋白 7B2 自身抗体频繁出现

Iwasaki M, Yonekawa T, Otsuka K, Suzuki W, Nagamine K, Hase T, Tatsumi K, Horigome T, Notomi T, Kanda H: "Validation of the Loop-Mediated Isothermal Amplification Method for Single Nucleotide Polymorphism Genotyping with Whole Blood."Genome Letters. 2,3.

Iwasaki M、Yonekawa T、Otsuka K、Suzuki W、Nagamine K、Hase T、Tatsumi K、Horigome T、Notomi T、Kanda H：“全血单核苷酸多态性基因分型的循环介导等温扩增方法的验证”。

Iwasaki M: "Validation of the Loop-Mediated Isothermal Amplification Method for Single Nucleotide Polymorphism Genotyping with Whole Blood"Genome Letters. 2,3. 119-126 (2003)

Iwasaki M：“全血单核苷酸多态性基因分型的环介导等温扩增方法的验证”基因组快报。