Systemic growth promoting actions of copper in weanling pigs

Abstract

The major objectives of this research were to examine whether copper (Cu) exerts its growth promoting actions systemically, to assess the role of feed intake in Cu-stimulated growth and to investigate the effect of Cu on the growth control system. An economical and convenient bioassay system using non-fusing myogenic BC₃H₁ cells and a MITT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide ) cell proliferation assay was developed, which measures serum mitogenic activity, an indicator for blood growth factor activity. The potential use of a previously reported cobalt-copper antagonism in reducing tissue Cu deposition in pigs fed high Cu diets was evaluated in two experiments using a total of 192 pigs. Feeding 150 or 300 ppm of inorganic cobalt (Co) as Cobalt Chloride reduced Cu deposition in the kidney, but failed to reduce Cu deposition in the liver and brain as reported in rats. Dietary Co of 150 ppm was found to be detrimental to weanling pigs. Therefore, inorganic Co feeding is of limited use in studying Cu-stimulated growth. The effect of intravenously injected Cu on growth was studied in two experiments with a total of 89 pigs. Amounts of Cu injected were calculated to simulate varying absorption rates in pigs fed 250 ppm of dietary Cu. Injecting appropriate amounts of Cu (calculated using digestibility of 5 % in Exp. 1 and 2-4 % in Exp. 2) promoted growth by 12-31 % (P < .05). Copper injections also stimulated serum mitogenic activity. Pituitary growth hormone (GH) mRNA was not significantly affected by Cu injections. This study suggests that Cu may stimulate growth systemically, without acting in the gastrointestinal tract as proposed by the antimicrobial hypothesis. The importance of feed intake in Cu-stimulated growth was examined in two experiments with a total of 138 pigs. Pair-feeding (Exp. 1) and restricted feeding (Exp. 2) were used to equalize the feed intake of pigs fed high Cu diets to that of pigs fed basal diets. Both experiments showed that Cu-stimulated growth was greatly reduced when Cu-fed pigs were restricted to have the same amount of feed as the control, which indicates that enhancing feed intake is an important part of the growth promoting mechanism of Cu. Copper feeding also enhanced serum mitogenic activity and increased pituitary GH mRNA concentration, independently of feed intake. This suggests that Cu feeding also affects the growth control system directly. In Exp. 2, Cu-lysine (providing 200 ppm dietary Cu) was found to be more effective than Cu sulfate in promoting growth. This benefit of Cu-lysine was largely from an increase in feed intake. This research demonstrated that Cu is able to promote growth systemically; and identified the importance of feed intake and the growth control system for Cu-stimulated growth, which opens new areas for future research.