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

为了分离在该腺体中特异性表达的新转录本，通过生成垂体BodyMap数据库，鉴定了三个新的垂体特异性转录本，它们编码推定的蛋白质：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和有效诊断该病，我们开发了实验室检测方法。采用重组人35s标记蛋白进行放射配体检测，检测垂体特异性蛋白GH、PGSF1a和PGSF2的自身抗体，以及垂体中表达的激素原转化酶（PC） 1/3、PC2、羧肽酶E （CPE）、α烯醇酶和PC2调节蛋白7B2的存在。在淋巴细胞性垂体炎和其他垂体功能低下患者中检测到抗人GH、抗pgsf1a和抗pgsf2抗体（Ab），而在无功能垂体大腺瘤患者中未检测到。无功能垂体大腺瘤患者中抗pc1 /3或抗7b2抗体阳性的患者明显多于其他垂体疾病和健康对照。抗-烯醇化酶抗体不适合用于淋巴细胞性垂体炎或垂体无功能腺瘤的特异性诊断。检测GH、PGSF1a、PGSF2、PC1/3和7B2抗体可能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.