The aim of this study was to identify the neoplastic endocrine cells which contain growth hormone (GH) and prolactin (PRL), in the MtTW15 mammosomatotropic tumor, with ultrastructural immunocytochemistry. We used tumors recovered after 5 to 11 weeks of tumor development, from normal (untreated) rats and from rats treated with the progestin medroxyprogesterone acetate (MPA)--a stimulator of GH secretion in these tumors. Immunocytochemical staining was done with the peroxidase-antiperoxidase technique on ultrathin sections of tumor that had been fixed in glutaraldehyde and postfixed on osmium tetroxide. Immunospecific staining for PRL was found over small (150 nm) secretion granules, whereas staining for GH was deposited on the larger secretion granules (250 nm). Tumors from MPA-treated rats contained profuse numbers of neoplastic cells with large, GH-positive granules. Immunocytochemical staining for GH and PRL was also found in crinophagic, lysosome-like inclusions, particularly in cells that contained many secretion granules. The results support the hypothesis that GH and PRL are produced by separate neoplastic endocrine cell types in the MtTW15 mammosomatotropic tumor, and demonstrate the value of ultrastructural immunocytochemical analysis for functional classification of cell types in chromophobic pituitary adenomas.
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