SPONTANEOUS PITUITARY ADENOMAS OF THE PARS INTERMEDIA IN MICE AND RATS: HISTOPATHOLOGICAL AND IMMUNOCYTOCHEMICAL STUDIES

From the control groups of five 2-year carcinogenicity studies, we isolated and observed six pituitary adenomas of the pars intermedia in two mice and four rats by histopathological and immunocytochemical techniques for evidence of production of the following proopiomelanocortin (POMC)-derived peptides; adrenocorticotropic hormone (ACTH), α-melanocyte-stimulating hormone (α-MSH), β-melanocyte-stimulating hormone (β-MSH), γ-melanocyte-stimulating hormone (γ-MSH), and β-endorphin (β-END). Macroscopically, most adenomas were from slightly to moderately enlarged or colored dark red, and were well separated from the brain and surrounding tissues. Histologically, their cells were scarcely distinguishable from the normal pars intermediate cells, but they often contained abundant eosinophilic cytoplasms, were enlarged and occasionally elongated and arranged in parallel groups. Atypia was not seen regularly, but some mitotic figures were seen. Two large adenomas from rats revealed vacuolated cell nests and follicular structures with colloidal materials. Immunostainings of all adenomas in both mice and rats were positive for all antisera tested and scarcely differed from staining of normal pars intermediate cells except that the intensities among the antisera were not constant and often presented pale and speckled appearances. Since the cytoplasms of the vacuolated cell nests of two rat adenomas also reacted positively for POMC-derived peptides, it was clear that these nests also originated from the pars intermedia. No endocrinological abnormalities in other organs or tissues, including the adrenal glands, were detected in any adenoma-bearing animals. From this evidence, we concluded that the adenomas derived from pars intermedia were endocrinologically active and were producing POMC-related peptides in both mice and rats.