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Pituitary and Thyroid Gland Lesions Induced by 2-Mercaptobenzimidazole (2-MBI) Inhalation in Male Fischer-344 Rats

Department of Microbiology, Parasitology, and Pathology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, Laboratory Animal Resources Unit, Department of Animal Science, North Carolina A&T State University, Greensboro, North Carolina 27411

Donald J. Meuten

Department of Microbiology, Parasitology, and Pathology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606

John M. Cullen

Department of Microbiology, Parasitology, and Pathology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606

Jeffrey J. Collins

National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, Research Triangle Park, North Carolina 27709, Glaxo Inc. Research Institute, 5 Moore Drive, Research Triangle Park, North Carolina 27709

2-Mercaptobenzimidazole (2-MBI) is a member of the thioureylene compound family known for their potent antithyroid activity. Male Fischer-344 rats were exposed to 0.0, 3.13, 12.5, and 50.0 mg/m3 of 2-MBI via inhalation for 13 wk. Follicular cell hyperplasia occurred in the thyroid glands of rats from the 3 2-MBI treatment groups. Thyrotrophs in the pituitary glands from rats in these 3 groups were hyperplastic, and they had varying numbers of hypertrophic cells with either eosinophilic stippled cytoplasm or with eosinophilic globules within 1 or more large vacuoles that displaced the nucleus. These cells were compared by immunohistochemistry and ultrastructural examination to "thyroidectomy cells" within the anterior pituitary glands of thyroparathyroidectomized rats and were determined to be identical to them. Immunohistochemical staining for the β-chain of thyroid-stimulating hormone confirmed that the hyperplastic and hypertrophic cells were thyrotrophs. Ultrastructurally, hypertrophic cells in 2-MBI-treated rats and thyroidectomy cells in thyroparathyroidectomized rats had expanded cytoplasm containing either increased profiles of rough endoplasmic reticulum (RER) or one or more widely dilated cisternae of RER, which displaced other cellular organelles. 2-MBI appears to act comparably to other thioureylene compounds that have been shown to produce low serum concentrations of triiodothyronine and thyroxine, which results in thyrotroph hypertrophy and hyperplasia, resultant thyroid hyperplasia, and subsequent goiter.

Key Words: Thyrotroph • thyroid-stimulating hormone (TSH) • thyroid toxicity • thioureylene

Toxicologic Pathology, Vol. 21, No. 5, 456-464 (1993)
DOI: 10.1177/019262339302100505


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