Regulation of Inhibin .BETA. 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 betaA, 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 betaA and follistatin mRNA levels by reverse transcriptase polymerase chain reaction analysis. The mRNA levels of the other inhibin beta chains (inhibin betaB and betaC) were examined in a similar manner. The inhibin betaA 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 betaB 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 betaC 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 betaB and betaC chains may play a role in peroxisome proliferator-stimulated hepatocyte growth.