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/insulin-like 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 micrograms/day) or intermittently (four sc injections of 12.5 micrograms/day). At a daily dose of 50 micrograms, intermittent rGH produced greater weight gain [+29.7 +/- 0.8 g (mean +/- SE)] than continuous GH infusion (23.3 +/- 2.0 g; P less than 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 less than 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 micrograms/day; 0.27 +/- 0.02 U/ml; P less than 0.05). Continuous infusions of 50 and 250 micrograms 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 less than 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 up-regulation of liver GH receptors.
Maiter
D
D
Unité de Diabétologie et Nutrition, University of Louvain School of Medicine, Brussels, Belgium.
Underwood
L E
LE
Maes
M
M
Davenport
M L
ML
Ketelslegers
J M
JM
D000818:Animals; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D007016:Hypophysectomy; D007260:Infusion Pumps; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011981:Receptors, Prolactin / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000378:metabolism*; D013002:Somatomedins / Q000097:blood*
D011981:Receptors, Prolactin; D011986:Receptors, Somatotropin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D013006:Growth Hormone