Recombinant human insulin-like growth factor: testing the somatomedin hypothesis in hypophysectomized rats

• Published in: Journal of endocrinology Vol. 112; no. 1; p. 123
• Main Authors: Skottner, A, Clark, R G, Robinson, I C, Fryklund, L
• Format: Journal Article
• Language: English
• Published: England 01-01-1987
• Subjects: Animals; Blood Glucose - metabolism; Body Weight; Bone Development; Cartilage - growth & development; Cell Membrane Permeability; Growth; Growth Hormone - pharmacology; Hypophysectomy; Insulin-Like Growth Factor I - analogs & derivatives; Insulin-Like Growth Factor I - blood; Insulin-Like Growth Factor I - pharmacology; Male; Rats; Somatomedins - physiology
• ISSN: 0022-0795
• DOI: 10.1677/joe.0.1120123

The in-vivo biological activity of recombinant methionyl insulin-like growth factor I (met-IGF-I) was demonstrated in hypophysectomized rats by following blood glucose after an i.v. bolus injection of met-IGF-I; a dose-dependent decrease in blood sugar was seen. Membrane transport was studied using the non-metabolizable amino acid alpha-aminoisobutyric acid; stimulation was obtained with the highest dose used (90 micrograms/rat). To test the original somatomedin hypothesis, growth studies were performed in hypophysectomized rats. Two or three doses of met-IGF-I were given with three different administration regimes (i.v. or s.c. infusion, or s.c. injections twice daily) for 6 or 8 days. Little growth-promoting activity was observed, with a significant effect on body weight gain obtained only when met-IGF-I was given continuously at the highest dose used (180 micrograms/day). No effect was seen on the in-vivo uptake of radioactive sulphate into cartilage. Epiphyseal cartilage width increased slightly at the highest dose of met-IGF-I, but only when the hormone was given by infusion. When 180 micrograms met-IGF-I/day were given by injections, a significant effect on longitudinal bone growth was obtained (90 micron above control). The levels of IGF in the serum were not measurably increased after s.c. administration of met-IGF-I, whereas after i.v. infusion, significantly raised levels were obtained at the higher dose rates (3.0 +/- 0.3 and 2.8 +/- 0.1 units/ml). Growth hormone was much more effective than met-IGF-I even at 50-fold lower doses. Priming the animals with 10 mu. bovine GH/day followed by combined infusions of GH and met-IGF-I did not reveal any potentiating effects of met-IGF-I in the presence of GH. We conclude that met-IGF-I is a relatively poor growth-promoting agent when given systemically, and that somatomedins are more likely to act as local growth factors rather than as circulating mediators of the growth-promoting effects of GH.