Hepatic stimulator substance. Discovery, characteristics and mechanism of action

Hepatic stimulator substance is a unique, 12,000- to 18,000-dalton peptide found in the liver of weanling and regenerating, but not normal, adult rats. It has also been demonstrated in dogs, rabbits, and pigs. It is organ specific, both in vivo and in vitro, but species nonspecific. It induces liver growth after a 10- to 12-hr lag period, during which time new protein and RNA synthesis are required. The initial events induced by HSS in HTC hepatoma cells in vitro include a rapid influx of Na+ via the Na+/H+ antiport and a rapid influx of extracellular Ca2+. The rise in intracellular Ca2+ appears to be dependent on the influx of Na+ and the influx of Na+ is necessary, but not in itself sufficient, to stimulate DNA synthesis.