Neural Tissue within Anterior Pituitary Tumors Generated by Oncogene Expression in Transgenic Mice
作者:
Joel Schechter,
Jolene J. Windle,
Claudia Stauber,
Pamela L. Mellon,
期刊:
Neuroendocrinology
(Karger Available online 1992)
卷期:
Volume 56,
issue 3
页码: 300-311
ISSN:0028-3835
年代: 1992
DOI:10.1159/000126243
出版商: S. Karger AG
关键词: Transgenic mice;Tumors;Anterior pituitary;Neural tissue
数据来源: Karger
摘要:
Pituitary tumorigenesis occurs in a transgenic line of mice, α-T7, which carries a hybrid transgene composed of the 5’ flanking region of the human glycoprotein hormone α-subunit gene (1.8 kb) linked to the coding region of the SV40 T-antigen gene (α-Tag). Tumor foci were identified within the anterior pituitary of both male and female transgenic mice. In addition to a parenchyma with hypertrophied endocrine cells, mostly of the gonadotrope lineage, we here report the unexpected presence of neural tissue within the anterior pituitary, either as foci as large as 1.0 mm in diameter or greater, or in delicate bundles ramifying amongst the granulated parenchymal cells. Areas richest in neural tissue frequently were associated with tumor tissue composed of giant cells of three varieties, all with electron-lucent cytoplasm and similar organellar distribution including small secretory granules (80–160 nm diameter). In type I cells, the secretory granules were aligned at the plasma membrane; in type II cells, the secretory granules were distributed throughout the cytoplasm; type III cells formed colloid-filled follicles and their secretory granules rarely exceeded 100 nm diameter. These giant cells frequently had bizarre pleomorphic nuclei intensely immunopositive for T-antigen and cytoplasm which was lightly immunopositive for α-subunit, and immunopositive either for the LH-β or TSH-β subunits. Neural tissue contacted the normal granulated parenchymal cells directly, i.e., without a basal lamina or any connective tissue intervening, but only rarely formed synaptoid junctions with these granulated cells. Synaptoid junctions containing round, smooth vesicles, as well as dense core vesicles, were numerous between the neural processes themselves and between the neural tissue and the giant cells of the tumor tissue. These data suggest that in α-T7 transgenic mice the giant cells represent highly transformed gonadotropes or thyrotropes, and that a neurotrophic factor may be expressed by these transformed pituitary parench
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