Control of protein synthesis by thyrotropin and epidermal growth factor in human thyrocytes: role of morphological...

The effect of thyrotropin (TSH) and epidermal growth factor (EGF) on the synthesis of proteins has been studied using two-dimensional gel electrophoresis in primary cultures of thyroid cells developing as a monolayer or that remained associated as dense aggregates. (1) A 4-day treatment of monolayer cells by TSH or dibutyryl cAMP enhanced the synthesis of 26 proteins and decreased that of 19 others. (2) The synthesis of 29 proteins was similarly modified by TSH and dibutyryl cAMP in both types of culture organizations. Both agents stimulated the synthesis of thyroperoxidase and of proliferating cell nuclear antigen (PCNA)/cyclin and decreased that of actin and of a high Mr isoform of tropomyosin. (3) TSH induced the retraction of monolayer cells. Its effect on the synthesis of many proteins was mimicked by culturing unstimulated cells as dense aggregates instead of monolayers which similarly affected cell morphology. (4) EGF alone had no effect on protein synthesis in monolayer cells but it inhibited both the morphological changes induced by TSH and dibutyryl cAMP and the effect of these agents on the synthesis of 23 proteins including thyroperoxidase.

(1) TSH and cAMP induce both proliferation and the expression of differentiation in thyroid cells while EGF has a small mitogenic effect but a marked inhibitory action on differentiation expression; (2) many TSH (cAMP) and EGF effects on the pattern of protein synthesis might be related to morphological changes; (3) the expression of the differentiation marker thyroperoxidase and of the mitogenic marker PCNA/cyclin appears independent of cell configuration and morphology.