ARS | Publication request: Insulin-Like Growth Factor Type-1 Receptor Down-Regulation Associated with Dwarfism in Holstein Calves

Submitted to: Domestic Animal Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 18, 2006
Publication Date: June 12, 2006
Citation: Blum, J.W., Elsasser, T.H., Greger, D.L., Wittenberg, S., de Vries, F., Distl, O. 2006. Insulin-like growth factor type-1 receptor down-regulation associated with dwarfism in Holstein calves. Domestic Animal Endocrinology. Available:http://dx.doi.org/doi:10.1016/j.domaniend.2006.05/007/

Interpretive Summary: Genetically inheritable altering growth is a problem in the animal production industry. In order to accurately determine the cause of such problems, knowledge and information on the underlying cause is necessary so that animals harboring these defects can be identified and culled from breeding populations. The present study documents cases of dwarfism occurring naturally in a population of European cattle. We have assessed several endocrine hormone traits and determined that the defect is not an insufficient supply of naturally occurring hormones that regulate growth, but rather a problem inherent in the animal¿s cells associated with the inability for the cells to respond to the growth signals. The exact problem is caused by a problem in the expression of receptors for a class of growth regulating hormones called insulin-like growth factors.

Technical Abstract: A phenotypic presentation of dwarfism in calves was studied to define perturbations in the endocrine interactions that impact normal growth. Three red and white German Holstein dwarf calves exhibiting retarded but proportionate growth were studied in addition to 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 and 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-hour period were similar, but the integrated GH concentration content (area under curve) were different (dwarfs > controls; P < 0.02; half-siblings > controls; P = 0.08). Relative gene expression of GH, 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 skeletal (anconeus) muscle by real-time RT PCR. Hepatic GHR mRNA levels were different (dwarfs < controls, P < 0.002; dwarfs < half-siblings, P = 0.06; half-siblings < controls, P = 0.08), but not in muscle. Hepatic IGF-1R mRNA abundance in half-siblings and controls were 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 ligand blot) were 2.5 times higher (P < 0.05) in half-siblings than in dwarfs. This was in agreement with the differences in IGF-1R content obtained by quantitative immunohistochemistry. (liver, P < 0.02; muscle, P < 0.07, dwarfs v. half-sisters, respectively). The data are consistent with the concept that a reduced presence of IGF-1R may be significant as an underlying cause of perturbed growth in calves and associated effects on the function of other somatotropic axis components.