Growth Hormone Stimulates Sequential Induction of c-myc and Insulin-Like Growth Factor I Expressionin Vivo*

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Abstract
The effect of GH administration to hypophysec tomized rats on expression of the c-myc proto-oncogene and insulin-like growth factor I (IGF-I) in the liver and kidney was examined. In both tissues maximal expression of c-myc occurred by 1 h after a single injection of human GH (100 μg/100 g bw). In the liver the maximal c-myc mRNA level was increased 12 ± 3.9-fold (mean ± SEM; n = 4), while the maximal c-myc level in the kidney was increased 3.4-fold (n = 2) compared to levels in basal hypophysectomized rats. In both the liver and kidney the IGF-I cDNA hybridized under stringent conditions to three transcripts with apparent sizes of 7.0, 1.8, and diffuse group of transcripts of 0.7–1.1 kilobases. Each of these transcripts demonstrated some degree of GH dependence. Under the hybridization condition used, the 7.0-kilobase IGF-I mRNA was virtually undetectable in the hypophysectomized control rat liver, while the smaller transcripts were easily detectable. Peak expression of each of the IGF-I transcripts occurred 6–12 h after GH administration. Maximal IGF-I expression in the kidney occurred 9 h after the GH injection. To determine whether the increase in c-myc expression following GH could result from a small but undetectable increase in IGF-I expression in these tissues, we administered human recombinant IGF-I to hypophysectomized rats (50 μg/100 g bw, ip). Despite a significant increase in serum IGF-I concentrations to levels greater than those present in the first 3 h after GH administration, no increase in c-myc expression was apparent in either the liver or kidney. These observations suggest that GH itself, rather than IGFI, initiates the mitogenic response in the liver and kidney that follows GH administration to hypophysectomized rats. (Endocrinology120: 1806–1812, 1987)