Body growth, carcass composition, and endocrine changes in lambs chronically treated with recombinantly derived insulin-like growth factor-I.

Castrate yearling male sheep were treated for 8 weeks with either 50 micrograms/kg body wt/8 hourly sc insulin-like growth factor-I (IGF-I) (n = 10) or with saline (n = 9). IGF-I treatment increased plasma IGF-I from 235 +/- 17 to 347 +/- 16 ng/ml (P less than 0.001). There was a gradual divergence in body wt (P less than 0.10) between treatment groups. Food intake did not change significantly. The weight of the spleen corrected for body wt increased by 40% (P less than 0.001) and there was a marginal increase in adjusted kidney wt (P less than 0.1). There was no effect of IGF-I on carcass weight or dimensions, or on long bone length, although the weight per unit length of the tibia (P less than 0.05) and femur (P less than 0.10) were increased. There was no effect on wool growth. Plasma IGF binding proteins (IGFBPs) were quantified by ligand blot analysis. In the IGF-I treated group, IGFBP-1 showed a transient increase (P less than 0.05) at day 3 but was similar in both groups at day 55 of treatment. IGFBP-2 was suppressed (P less than 0.05) by day 55 and IGFBP-3 and 4 did not change. Plasma glucose was elevated (P less than 0.05) and plasma insulin was suppressed (P less than 0.01) from 280 +/- 32 pg/ml to 124 +/- 30.4 pg/ml, plasma urea (P less than 0.01) and creatinine (P less than 0.05) were reduced in the IGF-I treated group. The somatogenic effect of IGF-I in this study was minimal suggesting that in the well fed animal with an intact somatotropic axis IGF-I treatment at doses which double plasma IGF-I does not enhance somatic growth performance. However, the marked splenomegaly shows the sensitivity of splenic growth to systemic IGF-I. The suppression of insulin with chronic IGF-I treatment was accompanied by hyperglycaemia--this may explain in part the lack of a significant anabolic response and may limit the utility of IGF-I therapy unless higher doses with insulin-like effects are used.