HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology



Morphological study of pituitary tumorigenesis in transgenic mice induced by hybrid oncogene of the thyrotropin Cortés and the simian virus 40 large T-antigen

Y. Kon1, I. Miyoshi2, K. Maki1, T. Yamashita1, S. Aoyama1, T. Watanabe1, Y. Hayashizaki3 and N. Kasai2

1Laboratory of Experimental Animal Science, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, 2Institute for Animal Experimentation, Tohoku University School of Medicine, Sendai and 3Gene Bank, RIKEN Tsukuba Life Science Center, The Institute of Physical and Chemical Research, Tsukuba, Ibaraki, Japan

Offprint requests to: Dr. I Miyoshi, Institute for Animal Experimentation, Tohoku University School of Medicine, Sendai 980-77, Japan

 

Summary. We have created a transgenic mouse, TIP-I, generating anterior pituitary tumors by using the simian virus 40 (SY40) large T antigen gene and human thyrotropin ~-subunit gene. To examine characteristics of tumors, histological details were investigated using light and electron microscopies. The main tumor tissues, composed of small chromophobe cells, were located inferior to but clearly separated from the hypothalamus; however, neuron fibers probably derived from the hypothalamus were observed to invade some tumor tissues. Some differentiated endocrine cells occupied the caudal region of the tumor. Immunohistochemically, SY40 large T antigen was expressed in the cell nucleus of the undifferentiated cell area, whereas cells expressing several hormones were mainly distributed in the differentiated cell area. Electron microscopically, the undifferentiated cells were divided into 2 types; electrondense and -lucent cells, the nuclei of which were composed of obscured nucleoli and many notable invaginations of the nuclear membrane. No intracellular microfilamentous structures were observed. Sometimes it was noted that cytoplasmic processes were connected with gap junctions. In the intercellular spaces, there were neuron fibrous and synapse-like structures. In the differentiated cell area, the cell membranes directly contacting other cells were relatively smooth, and many gap junctions were demonstrated. Secretory granules, which were round and less than 100 nm in diameter, were more electron dense in smaller cells than in larger cells. They were aligned just below the cell membrane. Immuno-electron microscopically, positive reactions for SY40 were observed in the nuclei of the undifferentiated cell area. In the differentiated cell area, most of the secretory granules were labeled by GH. TTP-l transgenic mice should provide a valuable animal model for studying the pathogenesis of anterior pituitary tumors. Histol Histopathol 12, 981-990 (1997)


Key words: Pituitary tumor, SY40 large T, Transgenic mice, Thyrotropin

DOI: 10.14670/HH-12.981