Liver impact of prolonged GH-treatment given to non-GH-deficient growing mice between the third and eighth week of life was evaluated in both sexes. Tissues were collected 6 h after last dose or four weeks later. Somatometric, biochemical, histological, immunohistochemical, RT-qPCR and immunoblotting determinations were performed. Five-week GH intermittent administration induced body weight gain and body and bone length increase, augmented organ weight, higher hepatocellular size and proliferation, and increased liver IGF1 gene expression. Phosphorylation of signaling mediators and expression of GH-induced proliferation-related genes was decreased in GH-treated mice liver 6h after last injection, reflecting active sensitization/desensitization cycles. In females, GH elicited EGFR expression, associated to higher EGF-induced STAT3/5 phosphorylation. Four weeks after treatment, increased organ weight concomitant to body weight gain was still observed, whereas hepatocyte enlargement reverted. However, basal signaling for critical mediators was lower in GH-treated animals and in male controls compared to female ones, suggesting signaling declination.