George S R, Kovacs K, Asa S L, Horvath E, Cross E G, Burrow G N
Department of Medicine, Toronto General Hospital, Ontario, Canada.
Clin Endocrinol (Oxf). 1987 Apr;26(4):395-405. doi: 10.1111/j.1365-2265.1987.tb00796.x.
The present study reports the effects of SMS 201-995, a long-acting somatostatin analogue, on blood GH levels, glucose tolerance and tumour morphology in a 36-year-old, previously untreated acromegalic woman. Treatment (50 micrograms s.c., 8-hourly) resulted in marked suppression of GH concentration and an improvement in glucose tolerance. After 10 d of treatment, the tumour was removed by transsphenoidal surgery and studied by histology, immunohistochemistry, transmission electron microscopy and morphometry. Histologically, the tumour was an acidophilic adenoma which contained immunoreactive GH in many adenoma cells. By electron microscopy, the tumour was composed of densely granulated somatotrophs containing numerous large secretory granules and many lysosomes showing crinophagy. No cell necrosis or vascular impairment were evident. Using morphometry, the tumour was compared with 10 densely granulated somatotroph adenomas, removed from acromegalic patients not treated with somatostatin. The nuclear and cytoplasmic areas of the adenoma subjected to SMS 201-995 treatment were smaller, and the lysosomes occupied more of the cytoplasmic volume than those of controls. The nuclear/cytoplasmic ratio, cytoplasmic volume densities of endoplasmic reticulum, Golgi apparatus, mitochondria, secretory granules and secretory granule diameters were within the range of control adenomas. In vitro, treated adenoma cells secreted GH and retained responsiveness to both GRH stimulation and somatostatin suppression. The morphologic findings after SMS 201-995 treatment, are consistent with suppression of GH release. There is no evidence that somatostatin has any direct cytotoxic or vasotoxic effects. It appears that SMS 201-995 represents a potent and promising drug in the medical treatment of acromegaly, however, more work is needed to elucidate the mechanism of somatostatin suppression and to provide evidence for adenoma shrinkage.
本研究报告了长效生长抑素类似物SMS 201-995对一名36岁、未经治疗的肢端肥大症女性患者的血液生长激素（GH）水平、糖耐量和肿瘤形态的影响。治疗（皮下注射50微克，每8小时一次）导致GH浓度显著降低，糖耐量得到改善。治疗10天后，通过经蝶窦手术切除肿瘤，并进行组织学、免疫组织化学、透射电子显微镜和形态计量学研究。组织学上，肿瘤为嗜酸性腺瘤，许多腺瘤细胞中含有免疫反应性GH。通过电子显微镜观察，肿瘤由密集颗粒化的生长激素细胞组成，含有大量大的分泌颗粒和许多显示自噬作用的溶酶体。未发现细胞坏死或血管损伤。使用形态计量学方法，将该肿瘤与10例从未接受生长抑素治疗的肢端肥大症患者切除的密集颗粒化生长激素细胞腺瘤进行比较。接受SMS 201-995治疗的腺瘤的核面积和细胞质面积较小，溶酶体占据的细胞质体积比对照组更多。核/质比、内质网、高尔基体、线粒体、分泌颗粒的细胞质体积密度以及分泌颗粒直径均在对照腺瘤的范围内。体外实验中，经治疗的腺瘤细胞分泌GH，并对促生长激素释放激素（GRH）刺激和生长抑素抑制均保持反应性。SMS 201-995治疗后的形态学发现与GH释放受抑制一致。没有证据表明生长抑素具有任何直接的细胞毒性或血管毒性作用。看来SMS 201-995在肢端肥大症的医学治疗中是一种有效且有前景的药物，然而，需要更多的研究来阐明生长抑素抑制的机制，并为腺瘤缩小提供证据。
