CONSEQUENCES OF POSTNATALLY ELEVATED INSULIN-LIKE GROWTH FACTOR-II INTRANSGENIC MICE - ENDOCRINE CHANGES AND EFFECTS ON BODY AND ORGAN GROWTH

Insulin-like growth factor-II (IGF-II) is an important regulator of em bryonic growth and differentiation, but its function in postnatal life is unclear. To address this point, we generated transgenic mice harbo ring fusion genes in which a human IGF-II complementary DNA is placed under the transcriptional control of the rat phosphoenolpyruvate carbo xykinase promoter. Transgene-specific messenger RNA was detected in li ver, kidney, and several parts of the gut. Serum IGF-II levels in tran sgenic mice were 2-3 times higher than those in controls and increased after starvation. Circulating IGF-I correlated negatively and IGF-bin ding protein-e (IGFBP-2) positively with IGF-II levels, suggesting tha t IGF-I is displaced from IGFBPs by IGF-II and that IGF-II is a major regulator of IGFBP-2. Serum levels of IGFBP-3 and IGFBP-4 tended to be higher in phosphoenolpyruvate carboxykinase-IGF-II transgenic mice th an in controls, as evaluated by ligand blot analysis. Starvation reduc ed serum IGF-I, but increased IGFBP-2 in transgenic mice more markedly than in controls. Fasting insulin levels were significantly reduced i n transgenic mice, whereas glucose levels were not influenced by eleva ted IGF-II. The body growth of 4- and 12-week-old mice was not signifi cantly influenced by elevated IGF-II, but transgenic mice displayed in creased kidney and testis weight at the age of 4 weeks, and increased adrenal weight at the age of 12 weeks. Our results demonstrate that el evated IGF-II in postnatal life has multiple endocrine consequences an d subtle time-specific effects on organ growth.