Modulating action of the thyroid on oestrogen-induced pituitary tumours in rats

The role of the thyroid gland in modifying the incidence of hyperplasia and tumor formation of estrogen-induced pituitary tumors was invesigated in experiments using a total of 184 adult albino rats of Wistar strain. Single pellets of estradiol benzoate were implanted subcutaneously in 173 of these rats. Thiourea and thiouracil were fed at a 0.5% level in the stock ration. Thyroxin was injected subcutaneously 3 times a week in doses of 20 mcg. A steady enlargement of the pituitary gland was induced by estradiol benzoate in normal adult rats. In some rats pituitary enlargement can be detected by the 50th day and the gland may have increased 40-fold in weight between the 100th and 150th day. Thyroxin administration accelerates development of pituitary tumors and leads to premature death of the rats. In rats bearing an estrogen pellet but fed thiourea or thiouracil the pituitary gland showed only mild hyperplasia. Although only 2 of 6 throidectomized rats treated with estrogen survived beyond the 100th day evidence suggests that thyroidectomy also prevented the pituitary gland enlargement and that even partial thyroidectomy appeared to counteract the estrogens effect. Pituitary enlargement was also effectively inhibited by dietary restrictions as well as feeding of antithyroid drugs. It is concluded that depression of thyroid function inhibits pituitary hyperplasia and tumor formation in estrogen-treated rats while thyroxin produces the reverse effect.