Monoclonal antibodies to growth hormone (GH) prolong liver GH binding and GH-induced IGF-I/IGFBP-3 synthesis
| Autor: | Jean-Marie Ketelslegers, Annie Robert, Robert Renaville, Daniel Portetelle, Pascale Lause, Véronique Beauloye, Séverin M Muaku, Dominique Maiter |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
medicine.medical_specialty
Hypophysectomy Physiology medicine.drug_class Endocrinology Diabetes and Metabolism medicine.medical_treatment Growth hormone receptor Monoclonal antibody Insulin-like growth factor-binding protein Physiology (medical) Internal medicine medicine Animals Bovine somatotropin RNA Messenger Insulin-Like Growth Factor I Rats Wistar Receptor Messenger RNA biology Growth factor Antibodies Monoclonal Receptors Somatotropin Rats Kinetics Insulin-Like Growth Factor Binding Protein 3 Endocrinology Liver Growth Hormone biology.protein Cattle Female |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 277:E308-E315 |
| ISSN: | 1522-1555 0193-1849 |
| Popis: | This time-course study further explored the mechanisms whereby monoclonal antibodies (MAbs) may enhance growth hormone (GH) effects. Hypophysectomized rats were killed 0, 1, 3, 6, 12, 24, and 48 h after a single injection of bovine (b) GH alone or complexed with an anti-bGH MAb. Serum insulin-like growth factor I (IGF-I) concentrations were increased more and for a longer period after MAb-GH complexes (peak at 24 h: 295 ± 24 ng/ml) than after bGH alone (peak at 12 h: 219 ± 37 ng/ml; P < 0.01), whereas liver IGF-I mRNA was similar at 12 h in both groups but remained higher at 24 h (by 65%, P < 0.001) and 48 h (by 64%, P < 0.001) in the presence of the MAb. Induction of serum insulin-like growth factor-binding protein (IGFBP)-3 and liver IGFBP-3 mRNA by bGH also was markedly amplified by the MAb (3.6- and 2-fold at 24 h, respectively; P < 0.01). GH receptors (GHR) remained occupied for a longer period after MAb-GH injection (36 ± 16 and 35 ± 8% at 6 and 12 h, respectively) compared with bGH alone (0 ± 28 and −15 ± 11%), whereas total liver GH-binding sites and GHR mRNA levels were not affected by the MAb. We conclude that MAbs against GH amplify and prolong the serum IGF-I response to GH, which may result from both a prolongation of liver IGF-I synthesis and an enhanced induction of IGFBP-3. These two effects may in turn be the consequences of sustained GH binding to its liver receptors in the presence of MAb. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|