Regulation of thyrotropin secretion in rats bearing the Walker 256 carcinoma

To evaluate the mechanisms whereby serum TSH was maintained in the normal range in tumor-bearing rats in association with decreased serum T4 and T3 concentrations, we studied the regulation of TSH secretion in groups of control (C) and T rats. The pituitary TSH contents were similar in the two groups of animals, and an iv injection of TRH (5 μg/100 g BW) resulted in a 10-fold increase in plasma TSH concentrations in the control group 15 min after injection. The TSH concentrations achieved after TRH injection were significantly greater in T rats than in the C group. A progressive 5- to 8-fold increase in plasma TSH was noted in both C and T rats after thyroidectomy. There was no difference in the integrated TSH response between these groups. Similarly, a smaller stimulus to TSH secretion did not produce significantly different effects on plasma TSH between groups of C and T rats. This was demonstrated in a study in which both groups of rats were fed 1-methyl-2-mercaptoimidazole [methimazole(MMI)] (10 μg/ml) in their drinking water. 5 days after the addition of MMI the mean plasma T4 level decreased from 3.6 +/- 0.5 to 2.7 +/- 0.6 (SEM) μg/dl (P<0.01). The mean plasma TSH level increased significantly (P<0.001) from 150 +/- 20 to 629 +/- 135 ng/ml in C rats and from 208 +/- 58 to 868 +/- 196 ng/ml in T rats after MMI treatment. The local production of T3 from T4 was studied in homogenates of pituitaries obtained from C and T rats. A mean 2.1-fold increase in the rate of T3 formation from T4 was noted in tissue from T rats. Lastly, the concentration of pituitary T3 in C and T rats was determined directly by RIA. The mean T3 content of T rats (18 +/- 1 pg/pituitary) was significantly decreased (P<0.001) from that of C rats