Effect of in vivo administration of recombinant acidic fibroblast growth factor on thyroid function in the rat: induction of colloid goiter.

Abstract

We have recently demonstrated that the iv administration of 0.6-60 micrograms/kg.day of acidic fibroblast growth factor (acidic FGF) increases thyroid weight in male and female rats. Interestingly, measurement of serum TSH and thyroid hormones in rats treated with 6 micrograms/kg.day acidic FGF for 30 days revealed only a slight increase in serum T4 and reverse T3 concentrations. Since thyroid function was only examined 24 h after the 30th daily treatment, we performed a series of experiments to evaluate the effects of acidic FGF on thyroid function following single and 6 multiple injections of acidic FGF. There was a small increase in the serum TSH concentrations at 2, 4, 8, and 24 h after a single high dose iv injection of acidic FGF (60 micrograms/kg). In contrast, serum T3 concentrations were slightly decreased at 2, 4, and 8 h after acidic FGF administration. There was no effect of a single injection of acidic FGF on serum T4, reverse T3, or thyroglobulin concentrations. After 6 days of treatment, there was a 34% increase in the thyroid weights of rats treated with acidic FGF. Analysis of serum hormones revealed a slight increase in serum TSH, T3, and T4 concentrations in acidic FGF-treated rats, but no change in serum reverse T3 or thyroglobulin concentrations. There was no effect of acidic FGF administration on thyroid radioiodine uptake, the intrathyroidal metabolism of radioiodine, or the relative amounts of thyroidal thyroglobulin or peroxidase messenger RNAs, or on liver 5'-deiodinase activity. In hypophysectomized rats, with no detectable levels of serum TSH, acidic FGF failed to increase thyroid weight. These data suggest that FGFs may participate with TSH in the regulation of thyroid weight and colloid accumulation, and that autocrine or paracrine growth factors may be involved in the pathogenesis of colloid goiter.