TRANSFORMING GROWTH-FACTOR-ALPHA IN-VIVO STIMULATES EPITHELIAL-CELL PROLIFERATION IN DIGESTIVE TISSUES OF SUCKLING RATS

Background-The role that exogenous transforming growth factor-alpha (T GF-alpha) may exert on cell proliferation in vivo is poorly understood . Aim-To investigate the effect of rat TGF-alpha on epithelial cell pr oliferation in all suckling rat digestive tissues and to compare it wi th that of rat epidermal growth factor (EGF). Animals and Methods-TGF- alpha and EGF were given three times daily either subcutaneously (10 o r 20 mu g/kg) or intraperitoneally (100 mu g/kg) to rats from the nint h postnatal day. Cell proliferation was assessed through 5-bromo-2-deo xyuridine incorporation and estimation of labelling indices. Results-F or both growth factors, the highest dose given for only two days signi ficantly increased stomach and intestinal weights compared with contro ls (p<0.05 to p<0.001). The proliferative responses depended on the do se given, colonic mucosa being the most sensitive whereas oxyntic muco sa remained unresponsive. TGF-alpha was as potent as EGF in stimulatin g epithelial cell proliferation in antral, duodenal, and colonic mucos ae. However, EGF was more active on oesophageal and jejunal cell proli feration whereas TGF-alpha was more active on pancreatic exocrine cell proliferation and the differences between the two growth factor treat ed groups were significant. Conclusions-These results prove for the fi rst time the stimulating effect in vivo of exogenous rat TGF-alpha on epithelial cell proliferation in rat digestive tissues during the deve lopmental period and support a functional role for TGF-alpha at that t ime.