Hepatic stimulator substance: physicochemical characteristics and specificity

Area of Science:

• Hepatology
• Molecular Biology
• Cellular Biology

Background:

• Previous studies indicated liver cytoplasmic extracts stimulated DNA synthesis in hepatectomized rats.
• The active component, hepatic stimulator substance (HSS), was not previously characterized in normal liver tissue.

Purpose of the Study:

• To investigate the effect of hepatic stimulator substance (HSS) on DNA synthesis in normal adult rats and mice.
• To characterize the properties and specificity of HSS.

Main Methods:

• Administration of HSS to normal adult rats and CF1 mice.
• Measurement of tritiated thymidine ([3H]dThd) incorporation into liver DNA.
• Autoradiography, heat stability tests, alcohol precipitation, ultrafiltration, dialysis, and organ specificity assays.

Main Results:

• HSS stimulated [3H]dThd incorporation into liver DNA in normal, non-hepatectomized rats and mice.
• The stimulation level in normal rats was comparable to that induced by 34% hepatectomy.
• HSS is heat-stable, alcohol-precipitable, has a molecular weight >10,000, and is liver-specific.
• Autoradiography confirmed [3H]dThd incorporation into nuclear DNA of parenchymal cells.

Conclusions:

• Hepatic stimulator substance (HSS) actively promotes liver DNA synthesis in non-hepatectomized animals.
• HSS exhibits properties of a heat-stable, organ-specific factor influencing liver regeneration.
• The findings suggest HSS plays a role in regulating liver cell proliferation.