Rats bearing transplanatable Walker 256 carcinomas have decreased hepatic nuclear T3 receptor concentration and decreased plasma concentrations of total and free T4 and T3. In the present studies, we investigated the mechanisms whereby plasma T4 is decreased in tumor-bearing (T) rats. Mean plasma T4 concentrations were significantly decreased in thyroidectomized T rats receiving daily treatment with T4 (3 μg/100 g BW). When tumor size was 6.5 ± 0.8% of body weight, plasma T4 was only 28% of control. This observation suggested alterations in the extrathyroidal metabolism of T4 in T rats. Measurements of plasma T4 binding and metabolism in groups of control (C) and T rats showed that the earliest change in thyroidal economy in rats with small neoplasms was a significant decrease in plasma T4 binding, and this was associated with a significant and proportional increase in the T4 MCR. With increasing tumor size, decreased plasma binding contributed to a smaller degree to the persistent elevation in the rate of T4 metabolism. This finding suggested that cellular processes involved in T4 metabolism were stimulated in T rats. Despite an increased rate of T4 metabolism in T rats, T4 turnover’ (nanograms per 100 g BW/h) remained unchanged from C or was significantly decreased. This appeared to be due to the fact that plasma TSH in T rats was similar to that in C rats, and thyroidal activity, assessed by the thyroid to serum iodide concentration ratio, was decreased in T rats. Thus, the decrease in plasma T4 in T rats appears to be due to a decrease in plasma T4 binding, an increase in the rate of cellular T4 metabolism, a failure of the hypothalamic-pituitary axis to augment TSH secretion in response to decreased plasma T4 and T3 concentrations, and a decrease in thyroidal activity based on either hyporesponsiveness to circulating TSH or secretion of abnormal TSH with decreased biological activity.
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