Methylprednisolone does not inhibit the release of growth hormone after intravenous injection of a novel growth hormone secretagogue in rats.
The present study was undertaken to study the growth hormone-releasing properties and growth-promoting effect of a GH secretagogue ipamorelin (IPA) in rats given the synthetic glucocorticoid methylprednisolone (MP). In a first experiment, rats received either saline or MP (5.0 mg/kg) for 8 days. Treatment with MP significantly (P< 0.001) decreased body weight gain, but the acute response to either IPA or growth hormone releasing hormone (GHRH) in terms of plasma GH was not changed. In a second experiment, venous catheters were surgically implanted. On the next day, rats were randomly allocated to receive saline alone, MP alone (5.0 mg/kg) or MP plus IPA in doses of 0.4 or 1.6 mg/kg/day for 10 days. IPA was administered intravenously four times a day.MP treatment significantly (P< 0.05) retarded recovery from surgery in terms of body weight. Thus, saline treated animals lost 4.0 +/- 3.5 g over the entire experimental period, whereas animals receiving MP lost 13. 6 +/- 2.9 g. When IPA was given together with MP, losses in body weight were significantly (P< 0.05) reduced to 2.3 +/- 2.0 and 1.6 +/- 2.0 g in animals given the high and low dose of IPA, respectively. In parallel with this IGF-I levels increased. In conclusion, this work shows that MP does not disrupt the response of the GH-IGF-I axis to an exogenous stimulus like IPA, and repeated stimulation leads to increases in IGF-I and of body weight gain.
Malmlöf
K
K
Departments of Pharmacological Research 3, Novo Nordisk A/S, Denmark. kmal@novo.dk
Johansen
P B
PB
Haahr
P M
PM
Wilken
M
M
Oxlund
H
H
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D013006:Growth Hormone / Q000097:blood*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008775:Methylprednisolone / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D006728:Hormones; D009842:Oligopeptides; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D008775:Methylprednisolone; C114611:ipamorelin