Type (3 transforming growth factor (TGF-fi), a factor produced by many cell types, is a potent inhibitor of hepatocyte DNA synthesis in vitro. To determine whether TGF-fi 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 (19,20).We studied the effect of intravenous porcine plateletderived TGF-f3, in amounts calculated to saturate hepatic TGF-,8 receptors, on the rate of DNA synthesis and the regeneration of liver mass induced by partial hepatectomy in the rat. We also studied the effects of TGF-,8 on liver morphology and blood concentrations of several liverderived or regulated substances.
MATERIALS AND METHODSPartial Hepatectomy. Male Sprague-Dawley rats (Holtzman, Madison, WI) weighing 182 + 14 g (mean ± SD) were given free access to water and a complete liquid diet (Dyets, Bethlehem, PA). They were individually housed under controlled lighting (lights on 0600-1800 hr). Normal weight gain and stable food intake were documented before study. Because of the striking diurnal variation in liver DNA synthesis after partial hepatectomy documented by Barbiroli and Potter (21), all rats underwent partial hepatectomy (PH) or sham hepatectomy between 1100 and 1500 hr. PH consisted of excision of the median and left lateral lobes, which comprise 69.2% ± 0.6% of the total liver weight (19,20). To control for the nutritional effects of PH, the group of sham-operated animals was pair fed with the PH group. In the 22 hr following the operation, PH rats consumed 13.7 ± 9.3 kcal (1 cal = 4.18 J), compared with 52.4 ± 9.3 kcal in the 24 hr preceding PH. Sham hepatectomy consisted of liver manipulation without ablation; sham hepatectomy animals were allowed a total of 14 kcal in the 22 hr after operation.Porcine TGF-f3, forms 1 and 2 (TGF-,81, TGF-,B2; R&D Systems, Minneapolis, MN), at 1.0 ,ug/ml in 4 mM HCl with 1 mg of bovine serum albumin per ml (0.5 ml), was injected into a tail vein at the times indicated. Bovine serum albumin/ Abbreviations: TGF-,3, type ,B transforming growth factor; IGF-I, insulin-like growth factor I; PH, partial hepatectomy. tTo whom reprint requests should be addressed at: Pediatric Endocrine-Metabolic Unit, ACC 609,