Hepatic stimulator substance: physicochemical characteristics and specificity

Abstract

This laboratory has reported previously that a cytoplasmic extract of weanling or regenerating adult rat liver (but not normal rat liver) will produce a 2.5-fold increase in the incorporation of tritiated thymidine ([3H]dThd) into liver DNA of a 34%-hepatectomized test animal. (J. Physiol. London 248: 273-284, 1975). The present study showed that hepatic stimulator substance (HSS) will stimulate DNA synthesis in normal adult rats and CF1 mice as well. The increased incorporation of [3H]dThd into DNA produced in the normal, nonhepatectomized adult rat was comparable with that induced by a 34% hepatectomy. Autoradiographic studies revealed that the [3H]dThd was incorporated into nuclear DNA and that the stimulation occurred almost exclusively in parenchymal cells. HSS was shown to be heat stable (100 degrees C for 15 min) and was precipitated but not inactivated by alcohol. Ultrafiltration and dialysis studies suggested a molecular weight slightly greater than 10,000. HSS proved to be organ specific, stimulating the liver but not the kidney, bone marrow, or spleen. HSS was found to contain no insulin, glucagon, epidermal growth factor, or peptides of the nonsuppressible insulinlike/multiplication-stimulating activity (somatomedin) group.

Induction of Hepatocyte Stimulating Activity by T3and Appearance of the Activity despite Inhibition of DNA Synthesis by Adriamycin

“…Humoral and cytoplasmic factors similar to HSA have been reported from a number of laboratories (LaBrecque and Bachur 1982;LaBrecque and Pesch 1975;Hatase et al 1979;Terblanche et al 1980;Moolten and Bucher 1967). All of these have in common that they can be extracted only or in greater quantity from proliferating liver or from the serum of rats in which the liver cells are proliferating.…”

“…HSA has been demonstrated in weanling rat livers (LaBrecque and Bachur 1982), and in the regenerating liver remnants of normal rats (LaBrecque and Pesch 1975;Hatase, Fujii, Kuramitsu, Itano, Takahashi, Murakami and Nisida 1979) and dogs (Starzl, Terblanche, Porter, Jones, Usui and Mazzoni 1979;Terblanche, Porter, Starzl, Moore, Patzelt and Hayashida 1980) after partial hepatectomy.…”

Growth induction of hepatic stimulator substance in he-patocytes through its regulation on EGF receptors

“…The animals were killed by cervical dislocation and the livers were removed immediately. HSS was extracted according to the method described by LaBrecque [7] and Fleig [3]. Briefly, the livers were flushed with Dulbecco'b phosphate-buffered saline (PBS, pH 7.4) via the portal vein, weighed and homogenated to 35% in PBS (w/v).…”

“…After a subtotal resection of adult rat liver, the remnant liver commenced to proliferate dramatically if the cytosol extract from weanling rat liver was administrated to the hepatectomized rats [19]. Since then, much effort toward the identification, purification and characterization of this growth-induced substance has been made [2,3,5].…”

Enhanced endoplasmic reticulum SERCA activity by overexpression of hepatic stimulator substance gene prevents hepatic cells from ER stress-induced apoptosis

“…A partial purification of the HSS protein indicated that the molecular size of HSS is 15ϳ18 kDa and that the protein is charac-terized by resistance to heat and pH but is protease sensitive (24). The biological function of the HSS protein is believed to be the stimulation of cellular DNA synthesis and mitosis (23). Intriguingly, several in vitro studies have demonstrated that although HSS stimulates cell growth in dividing hepatocytes, it is unable to stimulate proliferation in the restingstate adult liver.…”