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Autocrine and paracrine modulation of transforming growth factor expression was assessed in rat intestinal epithelial cell lines designated IEC-6 and IEC-7. Addition of the transforming growth factor alpha (TGF alpha) homologue epidermal growth factor (EGF) to media of subconfluent IEC-6 cells led to autocrine stimulation of TGF alpha expression as well as increased expression of the transforming growth factor beta 1 (TGF beta 1). Increased expression of TGF alpha was maximal between 3 and 6 h after addition of EGF and subsequently declined coincident with increasing level of expression of TGF beta 1, which achieved maximal levels 6 h after addition of EGF and was sustained for more than 12 h. Addition of TGF beta 1 also led to autocrine induction of its own expression coincident with suppression of TGF alpha expression. Addition of TGF beta 1 was associated with increased expression of beta-actin when standardized to a constitutive transcript (GAPDH). Similar responses to addition of EGF and TGF beta 1, were observed in another intestinal epithelial cell line, designated IEC-17. Modulation of expression of TGFs was attenuated when cells were grown on the complex extracellular matrix produced by the Engelbreth-Holm-Swarm tumor (Matrigel), reflecting the baseline induction of TGF beta 1 expression when compared to IEC-6 and IEC-17 cells maintained on plastic. These observations suggest that expression of TGFs is controlled by autocrine mechanisms in intestinal epithelial cell lines and proliferation stimulated by TGF alpha may be initially self-reinforcing but ultimately downregulated by induction of TGF beta 1.