Comparative and immunohistochemical analyses on hepatic zonation in vertebrates with a special reference to evolution.

The mammalian liver lobules have zonation for various hepatic functions. It remains to be precisely determined which vertebrate taxa exhibit the hepatic zonation. There are two types of liver architectures in vertebrates: the portal triad type (roughly vertebrates except teleosts) and the non-portal triad type (teleosts). The aim of the present study is to determine histochemically and immunohistochemically how the hepatic zonation is established in vertebrates with a reference to the liver architectures and evolution. As a result, the typical hepatic zonation of metabolic enzymes, such as phosphoenolpyruvate carboxykinase and Cyp1a2, was detectable in mammals, including the opossums, pigs, dolphins, guinea pigs, mice, and marmosets. They also consistently exhibited pericentral expression of glutamine synthase, one of ammonia-metabolizing enzymes, which was undetectable in other vertebrates. Murine livers had a more remarkable zonation of cell adhesion molecules and carbamoyl-phosphate synthase I, which other mammals did not exhibit. Chicken and Japanese quail livers showed zonation of alkaline phosphatase (ALP) activity in sinusoidal cells, but no zonation of metabolic enzymes. The amphibian and reptilian livers showed poor zonation. Although many actinopterygians did not exhibit hepatic zonation, some teleost livers showed zonation for the accumulation of periodic acid-Schiff-positive substances and sinusoidal ALP activity. Grass puffer exhibited zonation of transcription factors and cell adhesion molecules. These data indicated that hepatic zonation was not associated with the two types of liver architectures. Mammals and some teleosts may have acquired remarkable hepatic zonation during evolution. Zonation of pericentral glutamine synthase expression is unique to mammalian species among vertebrates.