Different Effects of Intermittent and Continuous Growth Hormone (GH) Administration on Serum Somatomedin-C/Insulin-Like Growth Factor I and Liver GH Receptors in Hypophysectomized Rats*

To determine if the pattern of GH delivery is important for the regulation of serum somatomedin-C/insulinlike growth factor I (Sm-C/IGF-I) and liver somatogenic receptors, we have measured serum Sm-C/IGF-I concentrations and free (H2O-treated homogenates) and total (MgCl2-treated homogenates) liver GH-binding sites in hypophysectomized rats treated for 7 days with rat GH (rGH), given either continuously by osmotic minipumps (50 and 250 μg/day) or intermittently (four sc injections of 12.5 μg/day). At a daily dose of 50 μg, intermittent rGH produced greater weight gain [+29.7 ± 0.8 g (mean ± SE)] than continuous GH infusion (23.3 ± 2.0 g; P < 0.01). Likewise, the serum Sm-C/IGF-I concentration rose more with intermittent (0.33 ±0.1 U/ml) than with continuous delivery (0.17 ± 0.01 U/ml; P < 0.01). The serum Sm-C/IGF-I level achieved with repeated GH injections was even greater than that after continuous delivery of a 5-fold higher GH dose (250 μg/ day; 0.27 ± 0.02 U/ml; P < 0.05). Continuous infusions of 50 and 250 μg rGH/day increased the number of liver total GH receptors by 2.5-fold over that of controls. In contrast, frequent GH injections did not affect GH binding, and the serum Sm-C/ IGF-I concentration did not correlate with liver GH-binding sites in the GH-injected rats (r = 0.189; P = NS). Induction of hepatic PRL receptors was 10-fold higher when GH was given continuously than when it was given intermittently. The close correlation observed between GH- and PRL- binding sites in all GH-treated rats (r = 0.955; P < 0.001) suggests that their regulation may be linked. These data suggest that the regulatory mechanism controlling Sm-C/IGF-I production and growth might be different from those that regulate GH receptor concentrations, with GH pulses being crucial for the maximal stimulation of Sm-C/IGF and growth, but continuous exposure to GH being required for upregulation of liver GH receptors. (Endocrinology123: 1053–1059, 1988)