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Characterization of Four Transplantable Mammotropic Pituitary Tumor Variants in the Rat¹

Department of Pathology, Cancer Research Institute and School of Public Health of Columbia University, New York, New York 10032

Four mammotropic tumor strains and the sera of the tumor hosts were assayed by immunoprecipitation for growth hormone and mammotropic hormone (MtH). Adrenocorticotropic (ACTH)-producing capacity was judged from changes in tumor hosts. The findings were correlated with morphologic changes in tumor hosts.

All four strains secrete growth hormone, MtH, and ACTH in varying concentrations characteristic of the strain. Two (F4 and Ba) are characterized by the production of large quantities of ACTH. ACTH production blocks anatomic manifestations of growth hormone, such as gain in body weight and thymus enlargement. Production of growth hormone by these strains is indicated by immunoassays and by the effects of adrenalectomy.

ACTH magnifies "prolactational" activity of the gland due to stimulation of milk secretion. This effect is also reversed by adrenalectomy.

The ¹³¹I excretion into the mammary glands in rats bearing these four strains was investigated as an index of ACTH activity. It was elevated in all four strains, most markedly in the two which produce large quantities of ACTH. Adrenalectomy greatly reduced ¹³¹I excretion in the mammary glands and milk secretion, the latter indicated by gross and microscopic findings. The residual secretory and excretory activity of the gland is probably due to other hormones of mammotropic tumors, notably MtH.

ACTH activity seems to have been acquired in the course of transplantation. It was not recorded at time of isolation of the large number of mammotropic tumors studied. This function became manifest in several strains in the course of subpassages but became prominent in two strains here surveyed. MtH and growth hormone activity was manifest in all tumor strains of this type soon after their isolation.

Of special interest in this connection are the hormone assays of Ba strain in comparison with those of Bi strain, from which it was derived. The Bi strain has high levels of MtH, moderate levels of growth hormone, and minimal levels of ACTH secretion. It was received by us as an originally inactive tumor which gave rise to the highly ACTH-secreting Ba variant.

The availability of these tumors secreting specific proteins now identifiable in nanogram quantities contributes to the carrying out of basic research related to hormones and neoplasia.

¹ These investigations have been supported by Grant CA-06215-07 of the National Cancer Institute, NIH.

² Research fellow of the Damon Runyon Memorial Fund for Cancer Research, Inc.

Received 3/26/68. Accepted 6/12/68.