Paracrine interaction between thyrocytes and fibroblasts.

Cell free supernatants (conditioned medium) of isolated porcine thyroid follicles, stimulated with EGF (5 ng/ml) or TSH (1-1000 microU/ml), were tested for a mitogenic activity for fibroblasts. Whereas TSH-conditioned medium dose-dependently stimulated [3H]thymidine incorporation into DNA of fibroblasts, only a weak stimulation was found with EGF. However, when the changes in cell number were determined, a significant increase was only found with EGF-conditioned medium from thyroid follicles. The cause of this discrepancy is a dose-dependent stimulation of [3H]thymidine incorporation into fibroblasts by cAMP and thyroid hormones. Cyclic AMP, however, does not stimulate growth of fibroblasts. IGF I production is stimulated in fibroblasts by basal as well as EGF stimulated conditioned medium of thyroid follicles. In contrast, TSH-conditioned medium inhibited IGF I production in fibroblasts. Conditioned medium itself is free of detectable IGF I. As IGF I stimulates not only growth of fibroblasts, but also of thyrocytes, we conclude, that conditioned medium from thyrocytes stimulates IGF I production in fibroblasts, which itself stimulates fibroblast and thyrocyte growth.