The proliferative responses of porcine thyroid follicular cells to epidermal growth factor and thyrotrophin reflect the autocrine production of transforming growth factor-beta 1.

The present study has investigated an involvement of autocrine transforming growth factor-beta 1 (TGF-beta 1) in regulating the proliferative response of porcine thyroid follicular cells (TFCs) to epidermal growth factor (EGF) and TSH. Primary monolayer TFC cultures exposed to EGF over the range 0-0.4 nmol/l showed a dose-dependent increase in [methyl-3H]thymidine incorporation, whereas higher EGF doses were associated with a reduction in the level of [methyl-3H]thymidine incorporation. TGF-beta immunoneutralisation had little effect on the stimulatory action of low EGF doses, but led to an increase in [methyl-3H]thymidine incorporation at higher EGF levels. In TFC cultures exposed to TSH, the level of [methyl-3H]thymidine incorporation attained at a dose of 1 U TSH/1 was enhanced in the presence of TGF-beta 1 antiserum, although the similar stimulatory effect of 8-bromo cAMP was unaffected. Treatment of TFCs with phorbol 12-myristate 13-acetate (8 nmol/l) to activate protein kinase C (PKC) led to an enhanced incorporation of [methyl-3H]thymidine which was increased further after neutralisation of endogenous TGF-beta 1. While confirming, therefore, a role for autocrine TGF-beta 1 in maintaining control of TFC DNA synthesis in vitro, these findings provide evidence that an increase in the availability of autocrine TGF-beta 1 effected by EGF and TSH may play an instrumental role in limiting the cellular hyperplasia induced by these factors within the thyroid follicular microenvironment. Moreover, the present data also suggest that the availability of active autocrine TGF-beta 1 to TFCs under such conditions may be dependent upon a PKC-mediated mechanism.