Boudouresque F, Lissitzky J C, Jaquet P, Guibout M, Goldstein E, Grisoli F, Oliver C
Horm Res. 1980;13(4-5):242-58. doi: 10.1159/000179293.
The immunologic patterns of 3 human pituitary adenomas of Cushing's disease have been studied after gel exclusion chromatography (Sephadex G-50). The immunologic characteristics were examined with three radioimmunoassays specific for human corticotropin (ACTH), lipotropin (LPH) and beta-endorphin (beta-End). In cell tumor extracts, chromatographic peaks corresponding to beta-LPH, gamma-LPH, beta-End and ACTH were identified. The ACTH/beta-LP-beta-End ratio was 1 in the 3 cases. Additionally, in the 3 cases, a chromatographic peak, partially cross-reacting in the beta-End assay, was eluted after beta-End, thus suggesting the presence of a fragment of the molecule. In 1 case, a peak of large molecular weight material with N- and C-terminal beta-LPH and ACTH immunoreactivity was observed, which corresponded to the precursor material. The release and the effects of various stimuli were studied on dispersed tumor cells in primary culture. The tumor cells had a biphasic basal secretion rate with a rapid increase of ACTH/beta-LPH-beta-End in the culture medium during the first 2 h. Then the release, studied during 2 days, was slower. Chromatographic studies showed that the beta-LPH/beta-End ratio was 0.8 in the cells and 0.3 in the medium, due essentially to the release of beta-End and beta-End-like materials. The cells released ACTH and beta-LPH-beta-End in equimolar ratio after stimulation with arginine vasopressin (AVP). The maximum effect was obtained with 10(-6) M AVP (D50 = 1 10(-9) M). Dibutyryl cyclic AMP (2. 10(-3) M) induced maximal release of ACTH/beta-LPH-beta-End. This stimulation was suppressed by a 48-hour preincubation with dexamethasone (10(-8)-10(-6) M). There was no effect of TRH and LH-RH on cell release. Dopamine (10(-6) M) specifically blocked the release of ACTH/beta-LPH-beta-End in 1 case. These data showed (a) heterogeneity of chromatographic profiles from case to case; (b) the presence of material in the tumor, cell extracts and culture medium corresponding to fragment(s) of beta-End; (c) culture studies demonstrated that tumor cells remain responsive to AVP stimulation and dexamethasone suppression, and (d) the dopamine inhibition of ACTH and beta-End release needs further investigation.
采用凝胶排阻色谱法（葡聚糖凝胶G - 50）研究了3例库欣病患者垂体腺瘤的免疫模式。使用三种分别针对人促肾上腺皮质激素（ACTH）、促脂素（LPH）和β - 内啡肽（β - End）的放射免疫分析法检测其免疫特性。在肿瘤细胞提取物中，鉴定出了对应于β - LPH、γ - LPH、β - End和ACTH的色谱峰。3例患者的ACTH/β - LP - β - End比值均为1。此外，在这3例患者中，有一个在β - End检测中出现部分交叉反应的色谱峰，在β - End之后被洗脱，提示存在该分子的一个片段。在1例患者中，观察到一个具有N端和C端β - LPH及ACTH免疫反应性的大分子量物质峰，其对应于前体物质。对原代培养的分散肿瘤细胞研究了各种刺激的释放情况及作用。肿瘤细胞具有双相基础分泌率，在最初2小时内培养基中ACTH/β - LPH - β - End迅速增加。之后在2天内的释放则较慢。色谱研究表明，细胞内β - LPH/β - End比值为0.8，培养基中为0.3，这主要是由于β - End及β - End样物质的释放。用精氨酸加压素（AVP）刺激后，细胞以等摩尔比释放ACTH和β - LPH - β - End。10⁻⁶ M AVP可产生最大效应（D50 = 1×10⁻⁹ M）。二丁酰环磷腺苷（2×10⁻³ M）可诱导ACTH/β - LPH - β - End的最大释放。用地塞米松（10⁻⁸ - 10⁻⁶ M）预孵育48小时可抑制这种刺激。促甲状腺激素释放激素（TRH）和促黄体生成素释放激素（LH - RH）对细胞释放无影响。多巴胺（10⁻⁶ M）在1例患者中特异性阻断了ACTH/β - LPH - β - End的释放。这些数据表明：（a）不同病例的色谱图谱存在异质性；（b）肿瘤、细胞提取物和培养基中存在对应于β - End片段的物质；（c）培养研究表明肿瘤细胞对AVP刺激和地塞米松抑制仍有反应；（d）多巴胺对ACTH和β - End释放的抑制作用需要进一步研究。
