title: 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.
authors.affiliation: Veterinary Physiology, Vetsuisse Faculty, University of Bern, CH-3012 Bern, Switzerland. juerg.blum@itz.unibe.ch
authors.forename: J W
authors.initials: JW
authors.lastname: Blum
authors.forename: T H
authors.initials: TH
authors.lastname: Elsasser
authors.forename: D L
authors.initials: DL
authors.lastname: Greger
authors.forename: S
authors.initials: S
authors.lastname: Wittenberg
authors.forename: F
authors.initials: F
authors.lastname: de Vries
authors.forename: O
authors.initials: O
authors.lastname: Distl
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000662:veterinary; D002417:Cattle; D002418:Cattle Diseases / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004392:Dwarfism / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*; D005260:Female; D005934:Glucagon / Q000097:blood / Q000235:genetics; D013006:Growth Hormone / Q000097:blood / Q000235:genetics; D007150:Immunohistochemistry / Q000662:veterinary; D007328:Insulin / Q000097:blood / Q000235:genetics; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology; D010375:Pedigree; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000097:blood / Q000235:genetics / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000097:blood / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D013974:Thyroxine / Q000097:blood / Q000235:genetics; D014284:Triiodothyronine / Q000097:blood / Q000235:genetics
chemical_list: D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D014284:Triiodothyronine; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone; D005934:Glucagon; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D013974:Thyroxine