Characterization of estrogen-induced adenohypophyseal tumors in the Fischer 344 rat.
Characterization of estrogen-induced adenohypophyseal tumors in the Fischer 344 rat.
复制标题
Fischer 344 大鼠中雌激素诱导的腺垂体肿瘤的特征。
作者：
C. Phelps;W. Hymer
用己烯雌酚(DES，8~10 mg)皮下埋植硅胶胶囊，对F344雌性大鼠进行慢性处理，诱发垂体肿瘤。在DES处理的1-150天的范围内，将对照和DES处理的大鼠对处死，并将它们的脑垂体酶解离为单细胞制剂。通过Ficoll-Hypaque分离和单位重力沉淀法检测细胞的总回收率、细胞重量、细胞内催乳素(PRL)含量和随后释放的催乳素(PRL)、免疫细胞化学PRL染色、密度和/或大小的变化，以及在吖啶黄素DNA染色后用激光流式细胞仪进行细胞周期分析。DES处理的脑垂体细胞总产量从处理8天的对照产量的1.3倍增加到150天对照的58.9倍。细胞内PRL含量为对照组的1.9~9.4倍，体外PRL释放量显著高于对照组，且持续高于对照组。在DES暴露8天后，PRL阳性细胞的免疫化学比例增加到总人口的50%以上。在两种类型的分离方案中，大多数PRL细胞群体的密度和/或大小和PRL含量都有所增加。DES的所有这些作用在以前去卵巢的动物中更加明显。这些数据扩展了其他研究人员的发现，进一步建立了DES诱导的肿瘤作为研究PRL细胞控制机制的模型。
Pituitary tumors were induced in F344 female rats by chronic treatment with diethylstilbestrol (DES, 8-10 mg) implanted subcutaneously in silastic capsules. Over a range of 1-150 days of DES treatment, pairs of control and DES-treated rats were sacrificed, and their pituitaries dissociated enzymatically into single-cell preparations. The cell populations were examined regarding total cell recovery correlated with gland weight, intracellular prolactin (PRL) content and subsequent release in primary culture, immunocytochemical PRL staining, density and/or size alterations via separation on Ficoll-Hypaque and by unit gravity sedimentation, and cell cycle analysis, after acriflavine DNA staining, by laser flow cytometry. Total cell yields from DES-treated pituitaries increased from 1.3 times control yields at 8 days of treatment to 58.9 times control values by day 150. Intracellular PRL content ranged from 1.9 to 9.4 times control levels, and PRL release in vitro was significantly and consistently higher than controls, after at least 8 days of DES exposure. Beyond 8 days of DES exposure, the immunochemically PRL-positive proportion of cells increased to over 50% of the total population. Increased density and/or size and PRL content were indicated for the majority of the PRL cell population in both types of separation protocols. All these effects of DES were more pronounced among previously ovariectomized animals. The data extend the findings of other investigators, further establishing the DES-induced tumor as a model for study of PRL cellular control mechanisms.