Hypophyseal isografts to sites remote from the hypothalamus in otherwise untreated female mice produce prolactin continuously. The excessive stimulation of the mammary glands by prolactin and progesterone in the graft-bearing animals may lead to mammary tumor formation.
The effect of isotransplantation of a single hypophysis at various sites (subcutaneous, intraperitoneal, spleen, ovary, kidney) in MTA-free (♂ O20 × ♀ IF)F1 female mice was investigated. Mammary tumor incidences of up to 80 per cent were observed in the experimental groups, as against a value of 2 per cent in the controls. Grafts of hypophyses of adult donors into the kidney were more effective than grafts into the spleen. Hypophyseal grafts of adult male donors were more effective than those of adult female donors. This sex difference was absent in the very potent grafts of infantile donors. Even grafts of a hypophysis of very old donors produced prolactin continuously and induced mammary tumors in the hosts.
Subcutaneous isografts of a single hypophysis frequently failed to “take,” but multiple subcutaneous grafts again proved efficacious. Multiple grafts into the kidney were more effective than single grafts.
Vaginal smear studies indicated that the effect of the hypophyseal grafts on mammary tumor formation was related to the amount of prolactin produced by the transplants in the course of time in the various experimental groups.
Many hypophyseal grafts showed progressive growth in the hosts. This phenomenon was most pronounced in the groups with a high mammary tumor incidence.
This investigation has been supported by a research grant C-3431 from the National Cancer Institute, U.S. Public Health Service.