Effect of thyroid status on development of spontaneous mammary tumors in primiparous C3H mice

Development of mammary tumors in primiparous C3H/HeN mice (mouse mammary tumor virus positive) in various thyroid states was followed for one year after removal of pups. Animals were either euthyroid or made hyperthyroid (by ingestion of thyroxine) or hypothyroid (by ingestion of 2-thiouracil) during involution. These manipulations resulted in significant changes in serum 3,5,3'-triiodo-L-thyronine and thyroxine levels without significant alterations in serum prolactin levels. At the end of one year postlactation, 90 to 86% of the euthyroid and hyperthyroid animals had developed mammary tumors, while the hypothyroid groups had only 70 to 72% tumor incidence. In two separate experiments, 50% tumor incidence was reached after 237 and 252 days in the hyperthyroid animals and after 242 and 252 days in the euthyroid groups. However, 50% tumor incidence in the hypothyroid groups was not reached until 290 and 287 days. The involuted mammary glands of all three groups were morphologically indistinguishable 10 weeks after removal of the pups. However, after 30 weeks, differences were seen. While glands from hyperthyroid and euthyroid animals retained a small degree of ductal branching with primitive alveoli, the glands from hypothyroid animals showed less ductal branching and were devoid of alveoli. Thus, the decrease in mammary tumor incidence in hypothyroid primiparous mice may be due to a greater degree of regression of the mammary epithelium in these animals.