Adams E F, Brockmeier S, Friedmann E, Roth M, Buchfelder M, Fahlbusch R
Department of Neurosurgery, Kopfklinikum, Erlangen, Germany.
Neurosurgery. 1993 Aug;33(2):198-203; discussion 203. doi: 10.1227/00006123-199308000-00003.
A subgroup of growth hormone (GH)-secreting pituitary tumors carries somatic mutations within the gene coding for the alpha subunit of the stimulatory heterotrimeric guanosine 5'-triphosphate-binding protein, Gs alpha. These so-called gsp mutations result in constitutively activated Gs alpha and the signal transduction cascade downstream of it, with eventual markedly and continuously elevated cyclic adenosine monophosphate levels as a result of constitutive adenylyl cyclase activity. It is this elevation of intracellular cyclic adenosine monophosphate that is thought to be the cause of excessive GH secretion and somatotroph proliferation. We examined the clinical and biochemical characteristics of acromegalics harboring gsp-positive and gsp-negative pituitary tumors. Of 19 tumors studied, 8 (42%) were gsp positive. There was a slight tendency for basal GH levels in serum to be lower and to be further reduced by an oral glucose tolerance test in gsp-positive patients. However, there was no difference between the two groups in terms of clinical features, tumor size, mitotic activity (as assessed by cytosolic deoxyribonucleic acid polymerase and KI-67 staining), and in vitro GH response to GH releasing factor. We conclude that there is, in general, little difference in the clinical and biochemical characteristics between gsp-positive and gsp-negative human pituitary GH-secreting tumors.
分泌生长激素（GH）的垂体瘤亚组在编码刺激性异三聚体鸟苷5'-三磷酸结合蛋白Gsα亚基的基因内存在体细胞突变。这些所谓的gsp突变导致Gsα持续激活及其下游的信号转导级联反应，由于腺苷酸环化酶持续活性，最终导致环磷酸腺苷水平显著持续升高。正是细胞内环磷酸腺苷的这种升高被认为是GH分泌过多和生长激素细胞增殖的原因。我们研究了携带gsp阳性和gsp阴性垂体瘤的肢端肥大症患者的临床和生化特征。在研究的19个肿瘤中，8个（42%）为gsp阳性。gsp阳性患者血清基础GH水平有轻微降低趋势，口服葡萄糖耐量试验后进一步降低。然而，两组在临床特征、肿瘤大小、有丝分裂活性（通过胞质脱氧核糖核酸聚合酶和KI-67染色评估）以及体外GH对GH释放因子的反应方面没有差异。我们得出结论，一般来说，gsp阳性和gsp阴性的人类垂体GH分泌肿瘤在临床和生化特征上几乎没有差异。
