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Dual Effects of Prolonged ACTH Stimulation on 4-Hydroxyaminoquinoline 1-Oxide-Induced Adrenocortical Lesions in Rats
Takayoshi Imazawa
Division of Pathology, National Institute of Health Sciences
Akiyoshi Nishikawa
Division of Pathology, National Institute of Health Sciences
Asahi Todate
Division of Pathology, National Institute of Health Sciences
Fumio Furukawa
Division of Pathology, National Institute of Health Sciences
Hiroshi Onodera
Division of Pathology, National Institute of Health Sciences
Kunitoshi Mitsumori
Division of Pathology, National Institute of Health Sciences
Masao Hirose
Division of Pathology, National Institute of Health Sciences
Yuzo Hayashi
Department of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan
The effects of a long-acting synthetic ACTH on 4-hydroxyaminoquinoline 1-oxide (4HAQO)-induced adrenocortical lesions were investigated in female rats. A total of 140 6-week-old rats were divided into 4 equal groups, given a single sc injection of 7 mg/kg 4HAQO or vehicle, followed by repeated sc administration of the synthetic ACTH or no further treatment. Subgroups of 10 rats in each group were sequentially sacrificed at weeks 20, 30, and 40. Adenomas and adenomatous nodules developed in the adrenal cortex of animals receiving 4HAQO and the chronic ACTH stimulation. Both lesions were located in the deeper zones of the adrenal cortex adjacent to the medulla and were composed of large-sized, clear-type cells. From week 20, middle zone, cortical cystic degeneration, which mimics the age-associated degenerative change named adrenal peliosis, was frequently observed in the adrenal glands of animals treated with 4HAQO alone. Its development was inhibited by ACTH. In the control animals, peliotic changes occurred at low incidence and only at the termination of experiment. These results indicate that long-term stimulation of ACTH promotes the development of adrenocortical tumors but suppresses the occurrence of adrenal peliosis in rats treated with 4HAQO.
Key Words: Synthetic ACTH • 4HAQO • SD rats • adrenal cortex • peliosis • tumors
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Toxicologic Pathology, Vol. 28, No. 4,
535-539 (2000)
DOI: 10.1177/019262330002800405
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[Abstract]
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