Characteristics of gsp-positive growth hormone-secreting pituitary tumors in Korean acromegalic patients.
Characteristics of gsp-positive growth hormone-secreting pituitary tumors in Korean acromegalic patients.
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韩国肢端肥大症患者 gsp 阳性生长激素分泌性垂体瘤的特征。
DOI：
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发表时间：
1996
影响因子：
5.8
通讯作者：
Y. Choi
中科院分区：
文献类型：
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作者：
I. Yang;S. Park;M. Ryu;J. Woo;S. Kim;J. Kim;Y. Kim;Y. Choi
人类生长激素(GH)分泌的垂体肿瘤的一个亚群包含GSP癌基因，该癌基因编码刺激性GTP结合蛋白(G(S)α)的α亚基的激活突变。本研究旨在探讨韩国肢端肥大症患者GH分泌型垂体瘤中GSP癌基因的频率及其内分泌检测的临床特点。直接聚合酶链式反应测序显示，21例肿瘤中有9例(43%)存在G(S)α蛋白201位氨基酸的GSP癌基因突变。在携带GSP癌基因的肿瘤中观察到一个单核苷酸突变，8个肿瘤用半胱氨酸(TGT)取代正常蛋白中的精氨酸(CGT)，1个肿瘤用丝氨酸(AGT)取代。GSP癌基因突变患者(组1)年龄(54+/-10vs41+/-11岁，p=0.0085)高于无突变患者(组2)。性别、肿瘤大小和分级、基础生长激素和催乳素水平、对口服葡萄糖负荷的生长激素反应、生长激素波动和对促甲状腺激素释放激素或促性腺激素释放激素的矛盾反应在两组之间没有差异。GSP癌基因主要见于生长激素腺瘤。奥曲肽对GH的抑制率第1组显著高于第2组(95+/-5%比81+/-17%，p=0.0335)。不同组间对溴隐亭的生长激素反应无差异。这些结果表明，韩国肢端肥大症患者存在生长激素分泌肿瘤G(S)α突变，其频率与西方国家相似。GSP癌基因携带者可能比无GSP癌基因携带者年龄更大，对奥曲肽表现出良好的GH抑制效应。
A subset of human growth hormone (GH)-secreting pituitary tumors contains the gsp oncogene that encodes an activation mutation of the alpha-subunit of the stimulatory GTP-binding protein (G(S) alpha). This study was undertaken to investigate the frequency of the gsp oncogene in GH-secreting pituitary tumors in Korean acromegalic patients and to elucidate the clinical characteristics of these patients to endocrine testing. Direct polymerase chain reaction sequencing revealed the gsp oncogene mutation in 9 out of 21 tumors (43%) at amino acid 201 of the G(S) alpha protein. A single nucleotide mutation in the tumors carrying the gsp oncogene was observed, which replaced an arginine (CGT) in the normal protein with cysteine (TGT) in eight tumors and serine (AGT) in one tumor. The patients with the gsp oncogene mutation (group 1) were older (54 +/- 10 vs 41 +/- 11 years, p = 0.0085) than those without the mutation (group 2). Sex, tumor size and grade, basal GH and prolactin levels, the GH response to oral glucose loading, the GH fluctuation and the paradoxical response to thyrotropin-releasing hormone or gonadotropin-releasing hormone did not differ between the groups. The gsp oncogene was found mostly in somatotroph adenomas. The octreotide-induced GH suppression was significantly higher in group 1 than in group 2 (95 +/- 5% vs 81 +/- 17%, p = 0.0335). The GH response to bromocriptine did not differ between the groups. These results suggest that the G(S) alpha mutations of GH-secreting tumor are observed in Korean acromegalic patients with similar frequency to those of western countries. The patients with gsp oncogene are likely to be older than those without the oncogene, and show excellent response of GH suppression to octreotide.