Thyroid Inhibition of Rats Bearing Transplantable, Hormone-Producing Pituitary Tumors

Abstract

Previous reports from this laboratory ( I ) have described the significantly reduced uptake of radioactive iodine, and the histology of an understimulated thyroid gland, present in rats implanted with hormone-secreting pituitary tumors. Thyroid inhibition also has been described in rats implanted with a malignant nonendocrine tumor (2,3) and in humans with a variety of cancers ( 4 ) .The tumor strain employed here was the MtTW5 which secretes prolactin and growth hormone but not TSH or ACTH. The hormonal properties of this tumor have been previously described (5,6). I t has been suggested that the thyroid inhibition of rats implanted with tumors ( 2 ) and of humans with cancers or chronic debilitating illnesses (7) is operated through nonspecific mechanisms such as a decrease in the thyroxine binding proteins, diminution which is just a participant in the generalized decrease of protein synthesis that goes on in those diseases. These possibilities were explored.Since thyroid suppression in the rats implanted with the pituitary tumors are not the result of the gland becoming unresponsive to TSH ( 1 ) , our attention was directed to the pituitary content of TSH and to some of the aspects of intrathyroid iodine metabolism that are affected by TSH. Materials and Methods. 1 ) Correlation of tumor size and thyroid inhibition of iodine uptake.Thirty-two adult \$%tar-Furth female rats were placed on regular Purina rat chow and tap water ad libitum. They were implanted S.C. in the right subscapular area with the MtTW5 tumor and were distributed in four cages containing eight rats each. On days 5, 8, 12,15, 20, 29, 36, 49 postimplantation, one rat from each cage was randomly selected, injected with 2 pC of carrier-free sodium ]:"I per 1 0 0 gm of body weight, and 18 hours later anesthetized with ether, and bled by cardiac puncture. Their thyroids and anterior pituitary glands were removed and weighed. One ml of serum and the thyroids suspended in 1 ml of saline were counted in a well scintillation counter.2 ) Levels of .free thyroxine ( T i ) in plasma were determined according to the equilibrium dialysis technique described by Ingbar et al. ( 8 ) . The serum extracted from one single rat was insufficient to carry out these studies on an individual basis, hence the serum from 2 4 rats was pooled.Control and tumor animals were matched by age and sex, but not by weight, because by virtue of the very same tumoral effects, the tumor-bearing rats were heavier.