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Effects of a Single Pituitary Isograft on Mammary Tumorigenesis in Mice^*

( Department of Anatomy, Baylor University College of Medicine, Houston, Texas)

Single pituitary isografts were transplanted either subcutaneously or intraocularly into female mice lacking the mammary tumor agent, DBA/2/f and (C57BL x DBA/2/f) F₁ hybrids, as well as mice with the mammary tumor agent, RIII and (RIII x C57BL) hybrids. All animals bearing a viable graft showed stimulated mammary glands with milk secretion and functioning corpora lutea. Such animals were capable of breeding and nursing their young. Mammary cancers developed in the agent-free DBA/2/f and (C57BL x DBA/2/f) F₁ hybrids mice with pituitary grafts. Pregnancy and lactation influenced mammary tumorigenesis in control RIII mice, but the milk secretion induced by a pituitary graft had a variable effect on tumorigenesis. Force-bred RIII females bearing a pituitary isograft developed mammary cancer at the same time as force-bred controls, suggesting a maximum threshold for hormonal stimulation in mammary tumorigenesis. RIII mice with grafts and allowed to nurse showed a later mean survival than did nongrafted mice. The C57BL strain contributes some form of "genetic resistance" to the (RIII x C57BL) F₁ hybrid as manifested by a delay in tumor appearance as compared with that in the force-bred RIII parent stock. This delay in time of tumor appearance was overcome by the effects of a pituitary isograft. The pituitary isografts in all strains showed an increase in size with time, whether transplantation was subcutaneous or intraocular, and appeared histologically similar to chromophobe adenomas. The results of this study indicate that a single pituitary isograft removed from its hypothalamic influences can have significant effects on the development of mammary cancers in intact mice depending upon genetic factors, the presence or absence of the mammary tumor agent, and the breeding history.

^* Presented in part and published in Proc. Am. Assoc. Cancer Research, 3:37, 1959.

Supported by U.S. Public Health Service grant C-4517.

Received 8/ 4/60.