Comparison of in vivo effects of insulin-like growth factors I and II and of growth hormone in hypophysectomized rats

Abstract

Abstract. Pure human IGFI (43 and 103 μg/day) and IGFII (131 μg/day) were infused into hypophysectomized rats during 6 days by means of sc implanted minipumps. Their effects on several growth indices were compared with those of various doses of sc infused human growth hormone. Growth hormone infusion produced a dose-dependent rise of endogenous rat IGF from 39 (without growth hormone) to 86 μU equivalents/ml (with 400 mU hGH/day) as determined by a competitive protein binding assay with a human IGF standard. In rats receiving the two doses of IGFI, total serum IGF levels rose to 83 and 99 μU equivalents/ml, respectively, in those receiving the IGFII dose the total serum IGF level rose to 146 μU equivalents/ml. These increases corresponded to steady state levels of 168 and 286 ng/ml of immunoreactive insulin-like growth factor (IR-IGF) I and 320 ng/ml of IR-IGFII. IGFI, but not IGFII led to an increase in body weight similar to that induced by the low doses of hGH (12.5 and 25 mU, respectively). The rise of endogenous rat IGF as well as the infused human IGFI and II caused a widening of the tibial epiphysis and an increase of the [3H]thymidine incorporation into costal cartilage. With respect to these two indices IGF II was clearly less potent that IGF I. When expressed in μU equivalents of the protein binding assay, endogenous rat IGF induced by hGH appeared to be relatively more effective than infused human IGF I or II. Growth hormone infusion produced a change in the radiochromatographic [125I]IGF binding pattern of hypox rat serum: the gammaglobulin-sized specific IGF binding peak that is characteristic of normal rat serum but lacking in serum of hypophysectomized rats reappeared. Neither infused IGF I nor IGF II had this effect. It may be concluded that the infusion of human IGF I or II in hypophysectomized rats produced qualitatively the same effects on growth indices as a growth hormoneinduced increase of endogenous rat IGF. This supports the idea that IGF I and to some extent also IGF II are able to mediate some of the actions of growth hormone. Other growth hormone effects appear to depend on growth hormone directly.