RESPONSES OF YOUNG ENERGY-RESTRICTED SHEEP TO CHRONICALLY ADMINISTERED INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) - EVIDENCE THAT IGF-I SUPPRESSES THE HEPATIC GROWTH-HORMONE RECEPTOR

We have shown previously that chronic administration (8 weeks) of insu lin-like growth factor-I (IGF-I) has little growth-promoting effect in well fed sheep. The aim of this study was to investigate the anabolic effects of IGF-I in energy-restricted conditions in which circulating concentrations of IGF-I in control animals were expected to be low. Y oung castrate male sheep were offered chaffed lucerne at a rate equiva lent to 110% maintenance and were treated by sc injection three times per day for either 8 or 12 weeks with recombinant human IGF-I(150 mu g /kg live wt . day) or saline in a 2 x 2 factorial design (eight animal s per cell). IGF-I treatment significantly increased plasma IGF-I conc entrations, but reduced plasma concentrations of IGF-II, GH, urea, and creatinine. Treatment with IGF-I also decreased (P < 0.1) GH secretio n in response to a GRF load, but significantly (P < 0.05) increased th e nonesterified fatty acid response to an epinephrine load. The reduct ion in circulating GH levels was accompanied by a suppression of [I-12 5]0GH binding to hepatic microsomal membranes. This effect, if apparen t in other tissues, may act as a feedback mechanism to limit the local synthesis of IGF-I and could explain why IGF-I treatment had little e ffect on the growth rate of the sheep, although it did increase nitrog en digestibility of the feed consumed and decreased the fat content of the hind leg. It also differentially promoted the growth of the splee n, thymus, and mandibular salivary gland and increased blood counts of eosinophils. It is concluded that IGF-I does not have marked effects on growth rate or body composition in sheep fed a near-maintenance die t. Possible reasons include the associated suppression of GH secretion and action, which limits the ability of treated animals to repartitio n absorbed nutrients.