Type. beta. transforming growth factor reversibly inhibits the early proliferative responsive to partial hepatectomy in the rat

Type {beta} transforming growth factor (TGF-{beta}), a factor produced by many cell types, is a potent inhibitor of hepatocyte DNA synthesis in vitro. To determine whether TGF-{beta} can influence hepatocyte proliferation in vivo, its effects were examined on the regenerative response of liver to partial hepatectomy (PH) in the rat. Porcine platelet-derived TGF-{beta}1, administered intravenously at the time of PH and 11 hr later, reduced the fraction of hepatocytes engaged in DNA synthesis 22 hr after PH by 67% and inhibited the rate of hepatic ({sup 3}H)thymidine incorporation by 50%. TGF-{beta}2 produced a similar effect. Although sensitive to TGF-{beta} administered 11 hr after PH, late in the G{sub 1} phase of the cell cycle, a single does of 0.5 {mu}g given at the time of PH did not significantly influence DNA synthesis 22 hr after PH. The inhibitory effects of TGF-{beta} were transient. The nuclear labeling index of the TGF-{beta}-treated animals was significantly higher than that of the controls. There was no evidence of cytotoxicity from TGF-{beta}, as determined by liver histology and plasma concentrations of glucose, insulin-like growth factor I, and two hepatic enzymes. Thus, TGF-{beta}1 and TGF-{beta}2 reversibly inhibit the proliferative response of liver to PH and may be important in the modulation of normal liver growth and repair.