Heterogeneity of the MtTW₁₅ mammosomatotropic tumor. II. Characterization of parenchymal cells by superimposition immunocytochemistry and electron microscopy

Abstract

Large MtTw15 tumors, which secrete growth hormone (GH) and prolactin (PRL), are composed of ovoid, elongated, and angular cells which demonstrated interdigitating processes and junctional complexes. The majority of the cells were essentially agranular, but two types of granulated cells were identifiable. One class of granulated cells contained moderate to sparse populations of round dense-cored granules measuring up to 250 nm in diameter. Rod-shaped to filamentous mitochondria with an electron-dense matrix were characteristic of a second class of granulated cells with plemorphic granules of various sizes and electron densities. Images of exocytotic release of the round dense-cored granules were frequently seen, but were not observed with the pleomorphic granules, many of which were judged to be lysosomes. Superimposition immunocytochemistry revealed hormones only in the granulated cells with round to ovoid granules. Morphometry indicated that hormone specific subpopulations of tumor cells can be identified since PRL secretory granules were significantly smaller than GH secretory granules (149 +/- 6 nm for PRL versus 221 +/- 9 nm for GH, P less than 0.001). The vast majority of immunopositive cells contained only GH or PRL, but a few were observed containing both hormones. Ovoid to irregular-shaped nuclei, large lipid inclusions, numerous free ribosomes and polyribosomes, moderate development of the rough endoplasmic reticulum, and prominent Golig profiles were characteristics of all cell types. Irrespective of the presence or absence of cytoplasmic granular elements, particles resembling viruses were encountered in many tumor cells, and these frequently appeared to be budding into the cisternae of the endoplasmic reticulum.

Double‐labeling immunogold electron‐microscopic study of hormonal colocalization in nontumorous and adenomatous rat pituitaries

“…Nakayama and Nickerson (1973) identified only one cell type by light microscopy and electron microscopy in Mlt-W 10 transplanted rat pituitary tumors which secreted both PRL and GH. In an immunohistochemical and electron microscopic study of the MTT W15 pituitary mammosomatotroph tumors, Tashjian et al (1970) and Parsons et al (1978Parsons et al ( ,1980 have shown that the majority of cells contained only PRL or only GH, but some adenoma cells were bihormonal and contained both. Using the reverse hemolytic plaque assay, Frawley et al (1985) and Leong et al (1985) documented that one pituitary cell can secrete both PRL and GH.…”

Ultrastructure of spontaneous and transplanted pituitary tumors in laboratory animals

“…Baskin et al (1980) examined the ultrastructural features of the MtT/W15 transplantable tumors with immunocytochemical labeling and found that PRL cells had small secretory granules with a mean diameter of 150 nm while GH was present in larger granules with a mean diameter of 250 nm. The studies of Parsons et al (1980) with immunocytochemistry revealed that many cells in the MtT/W15 tumors produced either PRL or GH, but that a small percentage of cells produced both PRL and GH. Estrogen treatment in rats with established MtT/W15 tumors has been shown to inhibit tumor growth and to increase GH secretion (Lloyd et al, 1985a).…”

“…Baskin et al, 1980;Lloyd et al, 1985a;Makino et al, 1984;McComb et al, 1984;Parsons et al, 1980;Schelin et al, 1964;Trouillas et al, 1984. Classification of Transplantable Pituitary Tumlors Many transplantable pituitary tumors have been established and successfully maintained by serial transplantation. The tumors that have been studied most extensively include the MtTIW5, MtT/W10, MtT/W15, MtT/F4, and 7315a.…”

“…Other techniques that have been used to induce pituitary tumors include blocking hormone synthesis with drugs such as propylthiouracil which affects thyroid hormone synthesis and use of pituitary isografts in various sites such as the anterior chamber of the eye and kidney capsule which can lead to PRL cell hyperplasia and tumor development. Baskin et al, 1980;Lloyd et al, 1985a;Makino et al, 1984;McComb et al, 1984;Parsons et al, 1980;Schelin et al, 1964;Trouillas et al, 1984. Classification of Transplantable Pituitary Tumlors Many transplantable pituitary tumors have been established and successfully maintained by serial transplantation. The tumors that have been studied most extensively include the MtTIW5, MtT/W10, MtT/W15, MtT/F4, and 7315a.…”

“…Estrogens and ergot alkaloids can also modify dopamine receptors as well as inhibit growth of transplantable pituitary tumors (Albaladejo et al, 1984;Iito et al, 1985;Lloyd and Fields, 1986a). Parsons et al (1980) observed ,small virus-like particles in the intercellular space and larger virus-like particles budding into the cisternae of the RER in MtT/ W15 transplantable tumors. The significance of these virus-like particles is not known, and the authors indicated that the tumor secretory function was not altered by the presence of these particles.…”