ENHANCED EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA-1 DURING THYROID HYPERPLASIA IN RATS

Transforming growth factor-beta 1 (TGF-beta 1) has been reported to influence the growth rate and iodine uptake and organification in vitro by isolated thyrocytes. We have determined changes in the expression and presence of TGF-beta 1 within the rat thyroid during goitre induction, and subsequent involution following goitrogen withdrawal. Hyperplastic goitres were induced in adult rats by administration of methimazole together with a low iodine diet for up to 12 weeks. Goitrogen-treated rats quickly became hypothyroid compared with controls, and exhibited thyroid hyperplasia and hypertrophy assessed by thyroid weight, and DNA and protein content (control: total serum thyroxine (T-4) 66 +/- 4 nmol/l, thyroid weight 5 +/- 1 mg/100 g body weight, mean +/- S.D., n=10; 2 weeks goitrogen: T-4 undetectable, thyroid weight 27 +/- 4 mg/100 g, n=10). Thyroid growth rate slowed subsequently between 2 and 10 weeks. Messenger RNA for TGF-beta 1 was compared in the thyroids and livers of control and goitrous rats by ribonuclease protection assay. Low levels of mRNA for TGF-beta 1 were detected in thyroids from control rats at all time-points, while TGF-beta 1 mRNA was barely detectable in liver. Thyroid TGF-beta 1 mRNA levels substantially and progressively increased at 1 and 2 weeks of goitrogen treatment respectively, and remained above control levels at 4 and 10 weeks. As thyroid involution occurred 4 weeks following goitrogen withdrawal, so thyroid TGF-beta 1 mRNA levels declined. In control animals, the cellular localization of TGF-beta 1 mRNA, determined by in situ hybridization, was found to be a subpopulation of follicular epithelial cells, and immunohistochemical co-localization of TGF-beta 1 and calcitonin identified these tentatively as parafollicular or C-cells. During goitre formation, abundant TGF-beta 1 mRNA and peptide were found to be widely distributed within the entire follicular epithelium. While this ubiquitous distribution had largely disappeared in the involuting gland, TGF-beta 1 peptide was retained within the parafollicular cells, which appeared more abundant than in thyroids from control animals. These results suggest that an increased local expression of TGF-beta 1, a putative growth inhibitor, during thyroid hyperplasia may contribute to the temporal stabilization of goitre size.