Transplantation of ACTH-secreting pituitary tumor cells in athymic nude mice

Chronic excess of glucocorticoids results in Cushing's syndrome in humans. A common cause of excess cortisol secretion is the presence of an adrenocorticotropin secreting pituitary tumor which stimulates the adrenal cortex to produce excess glucocorticoids. ACTH-secreting AtT-20 mouse pituitary cells transplanted subcutaneously in oestrogenized athymic nude mice form tumors rapidly. Six weeks after receiving the tumor transplants, the mice weighed 45% more than normal mice due to the increase in body fat. The tumor-bearing mice exhibit the familial "buffalo hump" appeaance due to the abnormal distribution of body fat. The adrenal glands of the tumor-bearing animals are enlarged due to hypertrophy of the zona fasciculata. The foamy looking fasciculata cells in normal mice were converted to dense, eosinophilic cells in the tumor-bearing mice. Transplantation of normal pituitary glands to athymic nude mice with or without oestrogen treatment did not produce these morphological changes. The experimental model described here may be useful for future studies of Cushing's syndrome.