Dual effects of prolonged ACTH stimulation on 4-hydroxyaminoquinoline 1-oxide-induced adrenocortical lesions in rats

The effects of a long-acting synthetic ACTH on 4-hydroxyaminoquinoline 1-ox ide (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 ad ministration of the synthetic ACTH or no further treatment. Subgroups of 10 rats in each group were sequentially sacrificed at weeks 20, 30, and 40. A denomas 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, cort ical cystic degeneration, which mimics the age-associated degenerative chan ge named adrenal peliosis, was frequently observed in the adrenal glands of animals treated with 4HAQO alone. Its development was inhibited by ACTH. I n the control animals, peliotic changes occurred at low incidence and only at the termination of experiment. These results indicate that long-term sti mulation of ACTH promotes the development of adrenocortical tumors but supp resses the occurrence of adrenal peliosis in rats treated with 4HAQO.