Dose-response effects of a new growth hormone receptor antagonist (B2036-PEG) on circulating, hepatic and renal expression of the growth hormone/insulin-like growth factor system in adult mice

• Published in: Journal of endocrinology Vol. 167; no. 2; pp. 295 - 303
• Main Authors: van Neck, JW, Dits, NF, Cingel, V, Hoppenbrouwers, IA, Drop, SL, Flyvbjerg, A
• Format: Journal Article
• Language: English
• Published: Colchester BioScientifica 01.11.2000; Portland Press
• Subjects: Animals; Apud cells. Peptide and protein hormones. Growth factors; Biological and medical sciences; Blood Glucose - metabolism; Body Weight - drug effects; Dose-Response Relationship, Drug; Eating - drug effects; Female; Fundamental and applied biological sciences. Psychology; Growth Hormone - blood; Growth Hormone - metabolism; Human Growth Hormone - analogs & derivatives; Insulin-Like Growth Factor Binding Proteins - blood; Insulin-Like Growth Factor I - metabolism; Kidney - metabolism; Liver - metabolism; Mice; Mice, Inbred BALB C; Organ Size - drug effects; Somatomedins - metabolism; Vertebrates: endocrinology; Digestive system; Liver; Rodentia; Somatotropin hormone; Kidney; Dose activity relation; Vertebrata; Insulin like growth factor; Mammalia; Urinary system; Adenohypophyseal hormone; Mouse; Antagonist; Biological receptor; Hormonal receptor
• ISSN: 0022-0795; 1479-6805
• DOI: 10.1677/joe.0.1670295

The effects of growth hormone (GH) in regulating the expression of the hepatic and renal GH and insulin-like growth factor (IGF) system were studied by administering a novel GH receptor antagonist (GHRA) (B2036-PEG) at different doses (0, 1.25, 2.5, 5 and 10 mg/kg/day) to mice for 7 days. No differences were observed in the groups with respect to body weight, food consumption or blood glucose. However, a dose-dependent decrease was observed in circulating IGF-I levels and in hepatic and renal IGF-I levels at the highest doses. In contrast, in the 5 and 10 mg/kg/day GHRA groups, circulating and hepatic transcriptional IGF binding protein-3 (IGFBP-3) levels were not modified, likely resulting in a significantly decreased IGF-I/IGFBP-3 ratio. Hepatic GH receptor (GHR) and GH binding protein (GHBP) mRNA levels increased significantly in all GHRA dosage groups. Endogenous circulatory GH levels increased significantly in the 2.5 and 5 mg/kg/day GHRA groups. Remarkably, increased circulating IGFBP-4 and hepatic IGFBP-4 mRNA levels were observed in all GHRA administration groups. Renal GHR and GHBP mRNA levels were not modified by GHRA administration at the highest doses. Also, renal IGFBP-3 mRNA levels remained unchanged in most GHRA administration groups, whereas IGFBP-1, -4 and -5 mRNA levels were significantly increased in the 5 and 10 mg/kg/day GHRA administration groups. In conclusion, the effects of a specific GHR blockade on circulating, hepatic and renal GH/IGF axis reported here, may prove useful in the future clinical use of GHRAs.