Growth hormone inhibits rat liver alpha-1-acid glycoprotein gene expression in vivo and in vitro

The gene encoding alpha-1-acid glycoprotein (AGP), one of the major acute-p hase proteins, is positively controlled at the transcriptional level by cyt okines (interleukin-1 [IL-1], IL-6, and tumor necrosis factor or) and gluco corticoids, Here, we show that growth hormone (GH) treatment of isolated ra t hepatocytes in vitro reduces AGP messenger RNA (mRNA) expression. AGP gen e expression remained inducible by IL-1, IL-6, and phenobarbital (PB) in GH -treated hepatocytes. Interestingly, the repressive effect of GH on AGP gen e expression was also observed in vivo: liver AGP mRNA content was strongly increased in hypophysectomized rats, and GH treatment of these animals led to a decrease in mRNA to levels lower than those in untreated control anim als, Moreover, the inhibitory effect of GH mainly occurs at the transcripti onal level and can be observed as little as 0.5 hours after GH adding in vi tro to isolated hepatocytes. These results show negative regulation of AGP gene expression and strongly suggest that GH is a major endogenous regulato r of constitutive AGP gene expression, Moreover, transfection assays showed that the region of the AGP promoter located at position -147 to -123 is in volved in AGP gene regulation by GH. Furthermore, GH deeply modifies the pa ttern of nuclear protein binding to this region. GH treatment of hypophysec tomized rats led to the release of proteins of 42 to 45 and 80 kd and to th e binding of proteins of 48 to 50 and 90 kd.