Enhanced expression of transforming growth factor beta 1 in rat thyroid hyperplasia is thyrotropin induced and time dependent

Forty-three 8-week-old male Wistar rats were studied to evaluate temporal changes of transforming growth factor beta(1) (TGF-beta(1)) mRNA levels in thyroid tissue during pharmacologically induced goiter. Four rats were treated with purified bovine thyrotropin (TSH; Ambinon, 2 mU/day sc) for 7 days before being sacrificed. Thirty-one were treated with propylthiouracil (PTU), added to their drinking water at a concentration of 0.2 g%, and subsequently were sacrificed as follows: five after 1 week (PTU-1); five after 2 weeks (PTU-2); five after 4 weeks (PTU-4): live after 8 weeks (PTU-8); five after 12 weeks (PTU-12). In six rats, after 12 weeks of treatment, PTU was withdrawn for 2 months and subsequently started again in three rats which were sacrificed after 2 weeks (PTU-R); the remaining three rats were sacrificed without any further treatment (PTU-R control). Eight rats (control rats) were never treated and served as controls. After sacrifice, blood was drawn for determination of total thyroxine and the thyroid was excised and subdivided into two lobes. Northern analysis for TGF-beta(1) was performed in one lobe, while histological and immunohistochemical studies were performed in the other lobe. Gene expression of TGF-beta(1) was induced in TSH- and PTU-treated rats. In TSH-treated rats TGF-beta(1) gene expression was less detectable than in PTU-treated rats, where it became evident after 2 weeks and remained through weeks 4-8. Gene expression of TGF-beta(1) was also seen in PTU-R rats, but not in the control and in the PTU-R control. Immunohistochemical analysis showed a different presence and location for the TGF-beta(1) protein, which appears to be dependent on the time of exposure to mitogenic stimulus. In conclusion, TGF-beta(1) is produced in response to both a direct (TSH by itself) and indirect (TSH induced by PTU-induced hypothyroidism) cellular proliferative stimulus and is not linked to an adaptative phenomenon secondary to hypothyroidism. The immunohistochemical location of TGF-beta(1) within the thyrocytes is influenced by mitogen exposure time. A TGF-beta(1) immunohistochemical evaluation may be important to define exposure time and activity of goitrogenic stimuli.