The effects of transforming growth factor alpha and somatostatin on regenerating hepatocytes in the rat

Transforming growth factor alpha (TGF alpha) stimulates DNA synthesis in adult rat hepatocytes, and plays a physiological role after partial hepatectomy by an autocrine mechanism. Somatostatin (SS-14) is a potent inhibitor of gastrointestinal function and inhibits proliferation in various cell types. We examined the proliferative effect of TGF alpha and the inhibitory effect of SS-14 on hepatocytes isolated at various times after partial hepatectomy. To study the mechanism of SS-14 further, we treated rats with the long acting SS-14 analog, octreotide, before or after 70% hepatectomy to determine whether or not a differential effect could be seen. We confirmed the proliferative effects of TGF alpha, and the inhibitory action of SS-14 in the early phase of liver regeneration in vitro. Regenerating hepatocytes isolated from hepatectomized livers respond to TGF alpha only at early time points (2 h) but do not respond to SS-14. In addition, the long acting SS-14 analog, octreotide, inhibited hepatic regeneration only when administered prior to hepatectomy. We conclude that exogenous peptide stimulation is effective only in the early phase of the hepatic proliferative response. After the initial changes brought about by hepatectomy, subsequent steps of the regenerative process appear refractory to external stimuli.