Adams E F, Lei T, Buchfelder M, Petersen B, Fahlbusch R
Department of Neurosurgery, University of Erlangen-Nurnberg, Germany.
J Clin Endocrinol Metab. 1995 Jul;80(7):2077-81. doi: 10.1210/jcem.80.7.7608258.
Gsp oncogenes are present in about 40% of somatotropinomas. They result in excessive cAMP production and have been proposed to be the cause of increased GH secretion. We have used in vitro cell culture to compare the biochemical characteristics of somatotropinomas with and without gsp oncogenes (gsp-positive and gsp-negative tumors, respectively). Of 30 somatotropinomas examined, 10 proved to be gsp positive, as determined by sequence analysis of DNA generated by the polymerase chain reaction. The somatostatin analog, octreotide, powerfully inhibited GH secretion by gsp-positive somatotropinomas, but had no effect on 8 of 13 gsp-negative tumors. Five of 20 gsp-negative and 4 of 10 gsp-positive tumors failed to respond to GHRH, whereas stimulatory effects ranging from 37-500% increases in GH secretion occurred in the remainder. However, strong stimulation (> 4-fold) occurred only in 5 of the gsp-negative tumors. The basal phosphatidylinositol turnover rate was elevated in about 25% of gsp-negative somatotropinomas. These results demonstrate similar and highly variable effects of GHRH on both types of somatotropinoma, whereas the absence of gsp oncogenes is often associated with resistance to octreotide. The phosphatidylinositol turnover data suggest that defects within this second messenger system may be present in a subset of somatotropinomas without gsp oncogenes.
Gsp癌基因存在于约40%的生长激素瘤中。它们导致cAMP过度产生，并被认为是生长激素分泌增加的原因。我们利用体外细胞培养来比较有和没有gsp癌基因的生长激素瘤（分别为gsp阳性和gsp阴性肿瘤）的生化特征。在所检测的30个生长激素瘤中，通过聚合酶链反应产生的DNA序列分析确定，有10个被证明是gsp阳性。生长抑素类似物奥曲肽能强烈抑制gsp阳性生长激素瘤的生长激素分泌，但对13个gsp阴性肿瘤中的8个没有影响。20个gsp阴性肿瘤中的5个和10个gsp阳性肿瘤中的4个对生长激素释放激素无反应，而其余肿瘤的生长激素分泌刺激效应在37%至500%之间。然而，强烈刺激（>4倍）仅发生在5个gsp阴性肿瘤中。约25%的gsp阴性生长激素瘤的基础磷脂酰肌醇周转率升高。这些结果表明，生长激素释放激素对两种类型的生长激素瘤具有相似且高度可变的作用，而缺乏gsp癌基因通常与对奥曲肽耐药有关。磷脂酰肌醇周转率数据表明，在一部分没有gsp癌基因的生长激素瘤中可能存在这种第二信使系统的缺陷。
