EFFECT OF THYROID-STIMULATING HORMONE ON THE DEVELOPMENT AND PROGRESSION OF RAT-THYROID FOLLICULAR CELL TUMORS

Time course changes in cell proliferative activity of thyroid focal hy perplastic and tumorous lesions as well as blood thyroid-related hormo nes in male F344 rats initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN: 2800 mg/kg body weight, single s.c. injection) were examined f ollowing chronic administration of 0.1% sulfadimethoxine (SM) in the d rinking water for 1, 4, 8, 12 and 16 weeks and at the end of a subsequ ent 4-week recovery period. Serum thyroid stimulating hormone (TSH) le vels increased rapidly from week I of SM treatment, reaching a peak at week 8, and then decreased gradually with prolongation of treatment p eriod, although remaining significantly elevated as compared with the corresponding controls at all time points up to week 16. Follicular ce ll hyperplasias and adenomas of the thyroid occurred from week 4 and c arcinomas from week 8. All of these lesions showed high cell prolifera tive activities corresponding to high serum TSH levels during the earl y stage, but the levels in hyperplasias and adenomas decreased rapidly with prolongation of SM treatment. After the recovery period, serum T SH levels had returned to below the normal range and cell proliferatio n in follicular hyperplasias and adenomas had stopped or was very low. Some carcinomas demonstrating invasive growth also showed remarkable decreases in the cell proliferative activity. The results of our study strongly suggest that a high serum TSH level plays an important role in the early stage pf thyroid tumorigenesis and that some tumors exhib iting invasive growth are still dependent on TSH stimulation.