Sanno N, Teramoto A, Osamura R Y, Genka S, Katakami H, Jin L, Lloyd R V, Kovacs K
Department of Neurosurgery, Nippon Medical School, Tokyo, Japan.
J Clin Endocrinol Metab. 1997 Aug;82(8):2731-7. doi: 10.1210/jcem.82.8.4175.
The functional and morphological changes in the pituitary gland caused by a GHRH-producing pancreatic islet cell tumor that metastasized to the pituitary and caused somatotroph hyperplasia are described. A 52-yr-old woman presented with loss of visual acuity, diabetes insipidus, and acromegaly caused by a GHRH-producing endocrine carcinoma metastasized to the pituitary. The serum GHRH, GH, and insulin-like growth factor I levels of the patient were elevated. Immunohistochemical and in situ hybridization study revealed GHRH immunoreactivity and GHRH messenger RNA (mRNA) in the metastatic tumor cells. The anterior pituitary showed hyperplasia of somatotroph cells with intact acinar structure that did not contain an adenoma, determined by light microscopy using silver impregnation. Electron microscopy revealed hyperplastic characteristics of densely granulated somatotrophs. In situ hybridization documented strong signals for GH mRNA and pituitary-specific transcriptional factor Pit-1 mRNA in the hyperplastic somatotrophs. A weak signal for GHRH receptor mRNA was detected in these somatotrophs. However, using in situ RT-PCR, GHRH receptor mRNA was more conclusively observed in most of the somatotrophs. The excessive production of GHRH by metastatic tumor may have resulted in somatotroph hyperplasia by the synergistic effects of Pit-1 and GHRH receptor. It can be concluded that the pathogenesis of pituitary adenoma formation is primarily mediated by other factors than hypothalamic hormone.
本文描述了一例生长激素释放激素（GHRH）分泌性胰岛细胞瘤转移至垂体并导致生长激素细胞增生所引起的垂体功能和形态学变化。一名52岁女性因GHRH分泌性内分泌癌转移至垂体，出现视力丧失、尿崩症和肢端肥大症。患者血清GHRH、生长激素（GH）和胰岛素样生长因子I水平升高。免疫组织化学和原位杂交研究显示转移瘤细胞中有GHRH免疫反应性和GHRH信使核糖核酸（mRNA）。通过银染光镜检查确定，垂体前叶生长激素细胞增生，腺泡结构完整，无腺瘤。电子显微镜显示密集颗粒型生长激素细胞的增生特征。原位杂交显示增生的生长激素细胞中GH mRNA和垂体特异性转录因子Pit-1 mRNA有强烈信号。在这些生长激素细胞中检测到GHRH受体mRNA的弱信号。然而，使用原位逆转录聚合酶链反应（RT-PCR），在大多数生长激素细胞中更确切地观察到了GHRH受体mRNA。转移瘤过度分泌GHRH可能通过Pit-1和GHRH受体的协同作用导致生长激素细胞增生。可以得出结论，垂体腺瘤形成的发病机制主要由下丘脑激素以外的其他因素介导。
