Roth K A, Newell D C, Dorin R I, Eberwine J H, Hoffman A R
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri.
Horm Metab Res. 1988 Apr;20(4):225-9. doi: 10.1055/s-2007-1010799.
A 64 year old woman with a pancreatic islet cell tumor developed Cushing's syndrome. Glucocorticoid secretion did not decrease after low or high dose dexamethasone administration, and the Cushing's syndrome was cured by removal of tumor tissue. Immunohistochemistry and radioimmunoassays revealed the presence of immunoreactive ACTH, beta-endorphin and alpha-MSH in the tumor cells. Gel-permeation chromatography confirmed that beta-endorphin was the predominant opioid peptide produced by the tumor. The tumor was shown to contain a single 1.2 kilobase RNA species which hybridized to a 32P human POMC-cDNA; this POMC RNA was identical in size to that isolated from a normal human pituitary. In dispersed monolayer culture, CRF failed to elicit ACTH release from the tumor cells, but dexamethasone caused a paradoxical increase in ACTH secretion in vitro. This study demonstrates that aberrant regulation of POMC synthesis and peptide processing can be seen in tumors which synthesize a POMC RNA identical in size to that made in the pituitary gland.
一名64岁患有胰岛细胞瘤的女性出现了库欣综合征。给予低剂量或高剂量地塞米松后，糖皮质激素分泌并未减少，切除肿瘤组织后库欣综合征得以治愈。免疫组织化学和放射免疫分析显示肿瘤细胞中存在免疫反应性促肾上腺皮质激素（ACTH）、β-内啡肽和α-促黑素（α-MSH）。凝胶渗透色谱法证实β-内啡肽是肿瘤产生的主要阿片肽。该肿瘤显示含有一种单一的1.2千碱基RNA，它与32P标记的人促肾上腺皮质激素原（POMC）-cDNA杂交；这种POMC RNA的大小与从正常人垂体中分离出的相同。在分散的单层培养中，促肾上腺皮质激素释放因子（CRF）未能促使肿瘤细胞释放ACTH，但地塞米松在体外却导致ACTH分泌出现反常增加。这项研究表明，在合成与垂体中大小相同的POMC RNA的肿瘤中，可以看到POMC合成和肽加工的异常调节。
