Insulin-like growth factor type-1 receptor down-regulation associated with dwarfism in Holstein calves

Abstract

Perturbations in endocrine functions can impact normal growth. Endocrine traits were studied in three dwarf calves exhibiting retarded but proportionate growth and four phenotypically normal half-siblings, sired by the same bull, and four unrelated control calves. Plasma 3,5,3′-triiodothyronine and thyroxine concentrations in dwarfs and half-siblings were in the physiological range and responded normally to injected thyroid-releasing hormone. Plasma glucagon concentrations were different (dwarfs, controls > half-siblings; P < 0.05). Plasma growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin concentrations in the three groups during an 8-h period were similar, but integrated GH concentrations (areas under concentration curves) were different (dwarfs > controls, P < 0.02; half-siblings > controls, P = 0.08). Responses of GH to xylazine and to a GH-releasing-factor analogue were similar in dwarfs and half-siblings. Relative gene expression of IGF-1, IGF-2, GH receptor (GHR), insulin receptor, IGF-1 type-1 and -2 receptors (IGF-1R, IGF-2R), and IGF binding proteins were measured in liver and anconeus muscle. GHR mRNA levels were different in liver (dwarfs < controls, P < 0.002; dwarfs < half-siblings, P = 0.06; half-siblings < controls, P = 0.08) but not in muscle. IGF-1R mRNA abundance in liver in half-siblings and controls was 2.4- and 2.5-fold higher ( P = 0.003 and P = 0.001, respectively) and in muscle tissue was 2.3- and 1.8-fold higher ( P = 0.01 and P = 0.08, respectively) than in dwarfs. Hepatic IGF-1R protein levels (Western blots) in muscle were 2.5-fold higher ( P < 0.05) and in liver and muscle (quantitative immunohistochemistry) were higher ( P < 0.02 and P < 0.07, respectively) in half-siblings than in dwarfs. The reduced presence of IGF-1R may have been the underlying cause of dwarfism in studied calves.