LONG R(3) INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) INFUSION STIMULATES ORGAN GROWTH BUT REDUCES PLASMA IGF-I, IGF-II AND IGF BINDING-PROTEIN CONCENTRATIONS IN THE GUINEA-PIG

We have tested whether an animal with substantial amounts of both IGF-I and IGF-II in circulation, such as the guinea pig, would respond to chronic IGF infusion in the same manner as the adult rat, which has negligible amounts of IGF-II in blood. Female guinea pigs of 350 g body weight were continuously infused for 7 days with recombinant guinea pig IGF-I or -II (120 or 360 mu g/day) or long R(3) IGF-I (LR(3)IGF-I) (120 mu g/day), an analogue which has much reduced affinities for IGF binding proteins. IGF-I or IGF-II infusion led to substantial increases in plasma IGF-I or IGF-II respectively in comparison with vehicle-infused animals. Nevertheless, body weight gain, feed intake, feed conversion efficiency and carcass composition were not significantly affected by any treatment (significance was deemed to be P<0.05). Amongst the tissues examined only the fractional weight (g/kg body weight) of the adrenals was increased, and that only by the higher dose (360 mu g/day) of IGF-I. However, the fractional weight of adrenals, gut, kidneys and spleen were significantly increased by LR(3)IGF-I, but again overall growth was not stimulated. A possible explanation for the lack of IGF-I effects is that total circulating IGF concentrations were not increased by these treatments. IGF-II significantly raised total IGF concentrations at the higher dose only. Plasma IGF-I was reduced by IGF-II infusion, as was plasma IGF-II by IGF-I infusion. LR(3)IGF-I treatment lowered both plasma IGF-I and IGF-II concentrations, a response probably related to a reduction in total plasma IGF binding protein (IGFBP), especially IGFBP-3, concentrations. We conclude that although the guinea pig is responsive to IGF treatment, the effects differ markedly from those elicited in rats.