Studies with Mouse Pituitary Thyrotropic Tumors. II. Restored Responsiveness in Semi-Responsive Strain Surgically Reduced in Size.∗

Discussion and Summary Tumor implants grown in radiothyroidectomized mice to 2 g in weight or more of an autonomous semi-responsive strain of mouse pituitary thyrotropic tumor, L24, lose their responsiveness to thyroxine. When these were reduced in size surgically to a diameter of about 0.5 cm, and the hosts fed thyroxine, no tumor became palpable over the space of 30 days, although the expected increase in tumor size occurred in similarly operated, untreated controls. The suppressed tumors promptly grew in the thyroxine treated group when thyroxine was stopped. The results suggest that the large non-responsive tumors had not been fundamentally altered in character and that the host mouse too had not undergone any fundamental change to account for loss of responsiveness. Decreasing concentrations of thyroxine reaching the tumor cell as the tumors grew larger would thus appear to be the most likely factor accounting for lack of responsiveness of this tumor strain. Nonetheless, provision of increased amounts of thyroxine, greater than the increase in tumor size would seem to require, fail to suppress growth of the larger tumors. Thus more is probably involved than hormonal concentration alone: perhaps limited blood supply to the tumor, perhaps loss of exogenous excess hormone from the body through overflow and excretion into the bile(3). In any event, it would appear that lethal amounts of thyroid hormone may have to be administered systemically if the minimal concentrations required to suppress growth of the larger tumors are to be reached.