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

Abstract

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.

Metabolic response of sheep skin to a chronic infusion of a variant of insulin-like growth factor I

“…Because of these similarities in structure, a number of studies have examined the effects of IGF-I on both food intake and glucose metabolism in large animals. It now seems clear that recombinant IGF-I has no effect on food intake in sheep, either when infused directly into the ventricle for 6 days [24] or when delivered by subcutaneous injection for 56 days [14]. The sheep in the present study showed a large variation in intake; however, during the first week of infusion of LR3IGF-I there was an indication of a decline in voluntary intake recovering to pretreatment intake after 8-9 days of treatment.…”

“…This suggests a direct response of insulin to circulating LR3IGF-I which over-rides any response to the initial reduction in endogenous IGF-I. A direct effect of IGF-I on insulin is reported in other studies by which treatment with IGF-I reduces plasma insulin concentrations when euglycaemia is maintained in dogs [6], rats [7], humans [8] and, in association with an increase in plasma glucose, sheep [14].…”

“…All of these studies were undertaken with starved animals, i.e. animals that were already in a catabolic state; one of the few long-term studies employing exogenous IGF-I in well-fed animals showed no change in carcass characteristics after 8 weeks of treatment [14]. Thus it is concluded that, with an adequate nutrient intake, the interactions between endocrine and paracrine mechanisms of IGF-I regulation return the body to normal homoeostasis as rapidly as possible.…”

“…In all of these studies, and many of the acute studies, two important points emerge: (1) animals are frequently in a catabolic state; (2) variants of IGF-I that are 'growth promoting' in rats have the opposite effect in pigs [13]. In addition, 56 days of IGF-I treatment of well-fed growing sheep resulted in little change in body weight and no effect on either carcass weight or wool production [14].…”

“…These infusions were only undertaken for 4 h and consequently it was not possible to assess whether the effects would be sustained over a longer term, and if so, whether there would be significant changes in the protein pools of the skin and therefore changes in wool production. Given the lack of response of wool production to the administration of exogenous IGF-I for 56 days [14], some caution needs to be exercised in extrapolating short-term results to longer-term effects of LR3IGF-I on skin metabolism and wool production. Therefore in the study reported here LR3IGF-I was infused into the skin of sheep for 21 days to allow measurement of wool production and any associated changes in wool-follicle characteristics such as bulb-cell replication rate.…”