Enhanced expression of transforming growth factor-β1 during thyroid hyperplasia in rats

Abstract

Abstract Transforming growth factor-β1 (TGF-β1) 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-β1 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 (T4) 66 ± 4 nmol/l, thyroid weight 5 ± 1 mg/100 g body weight, mean ± s.d., n = 10; 2 weeks goitrogen: T4 undetectable, thyroid weight 27 ± 4 mg/100 g, n = 10). Thyroid growth rate slowed subsequently between 2 and 10 weeks. Messenger RNA for TGF-β1 was compared in the thyroids and livers of control and goitrous rats by ribonuclease protection assay. Low levels of mRNA for TGF-β1 were detected in thyroids from control rats at all time-points, while TGF-β1 mRNA was barely detectable in liver. Thyroid TGF-β1 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-β1 mRNA levels declined. In control animals, the cellular localization of TGF-β1 mRNA, determined by in situ hybridization, was found to be a subpopulation of follicular epithelial cells, and immunohistochemical co-localization of TGF-β1 and calcitonin identified these tentatively as parafollicular or C-cells. During goitre formation, abundant TGF-β1 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-β1 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-β1, a putative growth inhibitor, during thyroid hyperplasia may contribute to the temporal stabilization of goitre size. Journal of Endocrinology (1994) 141, 45–57