Corticotropin assay with transplantable adrenocortical tumor slices: application to the assay of adrenotropic pituitary tumors.

Transplantable tumors of the adrenal and pituitary, which retain the capacity to secrete hormones characteristic of the cell from which they arose, have been isolated in mice. Adrenocortical tumors (8, 4) secrete corticoids in abundance and respond to corticotropin (AtH) even though they are highly malignant, as indicated by extensive metastases in the lungs and other organs. Several established adrenotropic tumor strains secrete AtH and no other pituitary hormone (5). The adrenotropic tumor syndrome (murine Cushing's disease) includes obesity (1, 5, 18), polyuria, polydipsia, lymphopenia, eosinopenia, and an extraordinary sensitivity to infections (5) and to acceptance of heterografts (6). The adrenal tumor syndrome (murine Cushing's syndrome) includes atrophy of the host's adrenal cortices, hypernatremia with profound polyuria, thymic involution, and eosinopenia (4). In earlier experiments (3) in which the response of the tumor slices to AtH was investigated in vitro, corticoid secretion could be elicited by a dose as small as 0.5 mU (International milliunits) of AtH. Response was proportional to the quantity of AtH added. The in vitro assay method for AtH, measuring the increase in production of total A~-8-ketosteroids by the tumor slices is, with some modification, that of Saffran and Schally (19) and McKearns and Norstrand (12), who have used normal rat adrenal slices. The method reported here is specific for AtH and has good precision and high sensitivity. The specificity of the assay was investigated with other tropic hormones and nonspecific proteins. This method was applied to measure AtH in the tumors and plasma of mice with several transplanted radiationinduced adrenotropic pituitary tumor strains and