Further steps of hepatic stimulatory substance purification

Abstract

The hepatic stimulatory substance (HSS) extracted from weanling rat livers was purified 381,000-fold using chromatographic techniques including nondissociating polyacrylamide gel electrophoresis (nondenaturing PAGE). The activity of this highly purified HSS, named Acr-F 4 , was assessed in two in vivo models. In 40% hepatectomized rats, it produced a fivefold increase in the proliferative rate normally seen following this partial hepatectomy. In Eck fistula dogs, the level of base increase in hepatocyte renewal was amplified threefold by an infusion of Acr-F 4 (50 ng/kg/day). Acr-F 4 had no influence on the regenerative response of the kidney following a unilateral nephrectomy or of the bowel following a 40% resection of the small bowel. On the basis of these findings, it can be concluded that HSS (Acr-F 4 ) has a high biological activity and is organ specific.

Screening for candidate hepatic growth factors by selective portal infusion after canine Eck's fistula

“…The amount of the other agents was guided by the previously determined effective dose by weight of HSS (13).…”

“…An in vivo canine model of portacaval shunt (Eck's fistula) has been used previously to demonstrate striking hepatotrophic qualities of insulin (3,4), crude (12) and partially purified (13) hepatic stimulatory substance (HSS) in the cytosol of regenerating livers and the immunosuppressive drugs cyclosporine (14) and FK 506 (15). In this study, the same technique has been used to test most other growth factors that have been reported to influence hepatocyte proliferation.…”

Isolation and functional identification of a novel human hepatic growth factor: Hepatopoietin Cn

“…Another substance purified from rat liver HSS, augmenter of liver regeneration, was shown to protect the hepatocyte of Eck's fistula from atrophy but had no effect on cultured hepatocytes and hepatic cell lines. 9,10 Therefore, we proposed that there must be other proteins with stimulatory activity in addition to augmentor of liver regeneration.…”

Hepatic regeneration and growth factors

“…During the last decade, evidence has been collected on the central role played by growth stimulating factors (GsF) [1][2][3][4][5][6][7][8][9] and growth inhibiting factors (GiF) [10][11][12] in the mechanism of tissue growth regulation, using different experimental models [13]. The model of partial hepatectomy (PH) in rats has provided numerous findings on the existence of this regulatory process.…”