Porcine epithelial cells in primary culture seeded on plastic substratum form a monolayer containing pseudo-vesicles. When cultured in the presence of thyreotropin (TSH) thyrocytes adopted a follicular-like structure and formed clusters. Transforming growth factor beta-1 (TGFbeta1) induced a rapid spreading of the TSH-treated cells only. At the same time, TGFbeta1 enhanced clusterin protein and mRNA expression. The increase of clusterin synthesis was proportional to the TGFbeta1 concentration in the culture medium. Tunicamycin abolished the up-regulation of whole clusterin synthesis and morphological changes. The activator protein-1 binding site partly directed the TGFbeta1-stimulated clusterin expression. Phorbol ester caused rapid spreading of the cells with disappearance of vesicular and follicular structures. It decreased clusterin mRNA and protein expression, but increased Mr 45, 000 protein secretion in both TSH-treated and nontreated cells. Up-regulation of clusterin expression may be a marker of TGFbeta-mediated thyrocyte dedifferentiation.