Regulation of Inhibin β Chains and Follistatin mRNA Levels During Rat Hepatocyte Growth Induced by the Peroxisome Proliferator Di-n-butyl Phthalate

Abstract

Peroxisome proliferators stimulate hepatocyte growth in rat liver in vivo. Activin A, a homodimer of inhibin β_A, inhibits DNA synthesis in hepatocytes. The inhibitory action of activin A is suppressed by follistatin, an activin-binding protein. In this paper, we investigated whether administration of di-n-butyl phthalate (DBP), a peroxisome proliferator, modifies the production of activin A and follistatin in rat liver by hourly monitoring of inhibin β_A and follistatin mRNA levels by reverse transcriptase polymerase chain reaction analysis. The mRNA levels of the other inhibin β chains (inhibin β_B and β_C) were examined in a similar manner. The inhibin β_A mRNA level decreased to about 30% by 3 h after DBP administration (8.6 mmol/kg body weight), remained low until 12 h, and returned to its original level by 24 h. The follistatin mRNA level increased to about 2 times by 6 h, and returned to its original level by 24 h. The inhibin β_B mRNA had started to increase by 1 h, peaked at 6 h at about 4 times its initial level, and returned to its original level by 12 h. The inhibin β_C mRNA level had doubled by 6 h and it returned to its original level. These results indicate that the growth stimulatory action of peroxisome proliferators may be mediated via the decrease in activin A level and activity and suggest that the increases in follistatin as well as inhibin β_B and β_C chains may play a role in peroxisome proliferator-stimulated hepatocyte growth.