K. Mitsumori et al., EFFECT OF THYROID-STIMULATING HORMONE ON THE DEVELOPMENT AND PROGRESSION OF RAT-THYROID FOLLICULAR CELL TUMORS, Cancer letters, 92(2), 1995, pp. 193-202
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.