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

为了分离在该腺体中特异表达的新的转录本，通过建立脑垂体图数据库，鉴定了3个新的脑垂体特异性转录本，它们编码可能的蛋白质：脑垂体特异性因子1a(PGSF1a)、PGSF1b和PGSF2。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。通过建立重组人35S标记蛋白的放射配基分析方法，分析了3种垂体特异性蛋白GH、PGSF1a和PGSF2以及垂体表达的5种酶--前激素转换酶(PC)1/3、PC2、羧基肽酶E(CPE)、α-烯醇化酶和PC2调节蛋白7B2的自身抗体的存在。抗人GH、抗PGSF1a和抗PGSF2抗体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，而在无功能垂体大腺瘤患者中未检测到。抗PC1/3和抗7B2抗体阳性者在无功能垂体大腺瘤患者中的发生率明显高于其他垂体疾病和健康对照组。抗PC2抗体和抗CPE抗体均为阴性。抗α-烯醇酶抗体不适用于淋巴细胞性垂体炎或无功能腺瘤的特异性诊断。检测抗GH、PGSF1a、PGSF2、PC1/3和7B2抗体有助于淋巴细胞性垂体炎的诊断。

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.