RAPID CHANGES IN GENE-EXPRESSION AFTER IN-VIVO GROWTH-HORMONE TREATMENT

GH exerts long-lasting effects on somatic growth via changes in gene e xpression and protein biosynthesis that represent the culmination of s ignal transduction pathways initiated at the cell surface. Recent stud ies have demonstrated that ligand-induced activation of the GH recepto r leads to the phosphorylation of multiple intracellular proteins, inc luding latent cytoplasmic transcription factors, Stats 1 and 3. GH tre atment also has been found to induce the expression of several genes i n both in vitro and in vivo systems, and we have shown that GH rapidly activates insulin-like growth factor I (IGF-I) gene transcription in hypophysectomized rats. In this study, using the GH-deficient, hypophy sectomized rat as a model, we have examined the earliest changes in ge ne expression that follow a single systemic injection of GH. We find t hat GH induces nascent nuclear IGF-I transcripts within 15 min of horm one treatment, a time course that parallels the GH-regulated appearanc e of nuclear c-fos messenger RNA (mRNA). By contrast, nuclear transcri pts for c-jun did not increase in abundance until after 30 min after h ormone injection, and the peak rise in c-jun mRNA was severalfold less than for c-fos or IGF-I. GH treatment also led to the acute inhibitio n of IGF binding protein-1 (IGFBP-1) and albumin gene expression. Nucl ear IGFBP-1 mRNA levels declined to 60% of baseline at 30 min and to 3 0% at 60 min, in agreement with previous studies showing a reduction i n IGFBP-1 transcription after GH. Nascent nuclear albumin transcripts also decreased in abundance after GH treatment to levels that were les s than 20% of basal values at 30 and 60 min. Our results show that GH can acutely activate and inhibit gene expression in the liver. It is l ikely that these diverse effects of GH are mediated by multiple signal transduction pathways.