MORPHOLOGY OF ADENOHYPOPHYSEAL TUMORS IN MICE TRANSGENIC FOR VASOPRESSIN-SV40 HYBRID ONCOGENE

Transgenic mice for the promoter sequence of bovine arginine vasopress in (AVP) gene fused to large SV40 T-antigen coding sequence develop pi tuitary tumors and insulin-producing pancreatic tumors. In order to es tablish the cellular composition of the pituitary tumors, histological , immunocyto-chemical, in situ hybridization, and electron microscopic technics were applied. Pituitary anterior lobe tumors were identified in 10 out of 14 glands examined. In 2 of these cases, intermediate lo be tumors were also found. The anterior lobe tumors contained a variab le number of GH immunoreactive cells. In situ hybridization performed in 7 cases revealed a diffuse distribution of GH messenger RNA over al l tumor cells. Ultrastructurally, the tumors contained undifferentiate d cells with very small secretory granules and rare cells showing some resemblance to somatotrophs. The results indicate that these pituitar y tumors are composed of undifferentiated somatotrophs. The presence o f a few PRL immunoreactive cells in four tumors and scattered TSH immu noreactive cells in two tumors supports the view that somatotrophs hav e the potential to produce PRL and TSH. The intermediate lobe tumors w ere immunoreactive for ACTH and intensely positive for POMC mRNA. In t he nontumorous adenohypophyses, no hyperplasia of any cell type was no ted. Several GH immunoreactive cells exhibited pleomorphic, giant nucl ei and mitoses. In conclusion, the majority of transgenic mice for AVP /large T-antigen develop pituitary tumors originating in and composed of somatotrophs. Less frequently, intermediary lobe tumors were presen t as well. AVP/SV40 transgenic mice provide a unique experimental mode l for somatotroph tumors that are neither preceded by, nor associated with somatotroph hyperplasia.