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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
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