A new transplantable rat
pituitary tumor was induced in F344 female rats with dimethylbenz(a)
anthracene and
estrogen (MtT/
F-DMBA) and studied for 20 serial transplant generations. The
tumor grew without
estrogen supplements in female rats by the second transplant generation. Sensitivity to
estrogens, as indicated by a prolonged latency period for
tumor development, was seen at the 20th, but not the 5th transplant generation. MtT/
F-DMBA tumors expressed
prolactin (PRL),
growth hormone (GH), and
adrenocorticotropin (
ACTH) mRNAs. A decrease in the percentage of cells expressing PRL
mRNA, PRL
protein, and in the number of secretory granules per cell occurred with serial
transplantation.
S-100 protein-positive folliculostellate cells were present in the hyperplastic pituitary but not in the transplantable
tumors.
Estrogen treatment at the 20th transplant generation prolonged the
tumor latency period, increased the number of cells expressing PRL
mRNA greater than 5-fold by in situ hybridization analysis (14 +/- 2% versus 77 +/- 5%), increased PRL secretion (132 +/- 40 ng/ml versus 3762 +/- 890 ng/ml), and increased the number of cytoplasmic secretory granules per cell. These results indicate that hyperplastic pituitary and true
pituitary neoplasms differ in their ability to grow readily after
transplantation. The presence of
S-100 protein-positive folliculostellate cells, which are present in hyperplastic but not in neoplastic pituitary tissues, may serve as a morphologic marker to separate hyperplastic and neoplastic rat pituitary tissues. Transplantable
tumors remained responsive to
estrogen with expression of a more differentiated phenotype, including an increased number of cells expressing PRL
mRNA and increased numbers of PRL secretory granules.