Short Communication: A Milk Trait-Associated Polymorphism in the Bovine Growth Hormone Receptor Gene Does Not Affect Receptor Signaling

Abstract

Growth hormone (GH), also known as somatotropin, stimulates milk production in cows. At the tissue level, the action of GH is mediated by the GH receptor (GHR) and the receptor-activated intracellular signaling pathway involving Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5). A T/A nucleotide variation in exon 8 of the bovine GHR gene, resulting in a phenylalanine to tyrosine change in the transmembrane domain of the GHR protein, has been reported to be associated with a major effect on milk yield in cows. The objective of this study was to determine whether the 2 versions of GHR differ in mediating GH-induced STAT5 activation of gene expression. We created cDNA expression plasmids for the 2 versions of GHR and cotransfected each of them with a STAT5 expression plasmid and a luciferase reporter gene construct containing STAT5 binding sites into 2 different cell lines. Treatment of the transfected cells with various concentrations of GH triggered a dose-dependent increase in luciferase activity. However, the GH-induced luciferase activity was not different between the 2 GHR expression plasmids, indicating that the 2 GHR forms did not differ in mediating GH-induced STAT5 activation of gene expression. Thus, if the T/A polymorphism in exon 8 of the GHR gene has a causative effect on milk production, this effect is unlikely to be mediated by the JAK2-STAT5 pathway, the currently known major signaling pathway from the growth hormone receptor.

Exploring polymorphisms and effects on milk traits of the DGAT1, SCD1 and GHR genes in four cattle breeds

“…Several mutations have been located within GHR, both in the 5′ UTR (Ohkubo et al, 2006) and in the coding region (Blott et al, 2003;Viitala et al, 2006). A nonsynonymous SNP in exon 8, causing the substitution of phenylalanine with tyrosine (F279Y) showed significant effects on milk composition and it seems that the effects of this mutation are consistent across breeds and populations even if the exact mechanism by which the F279Y amino acid change influences milk parameters is not clear (Zho and Jiang, 2006).…”

Growth Hormone Can Induce Expression of Four Major Milk Protein Genes in Transfected MAC-T Cells

“…The MAC-T cells at ∼60% confluency in 100-mm dishes were transfected with 10 g of a bovine GHR expression plasmid (Wang and Jiang, 2005) and 10 g of a STAT5 expression plasmid using transfection reagent FuGENE 6 (Roche Applied Science, Indianapolis, IN) as described previously (Zhou and Jiang, 2006). Twenty-four hours after the transfection, the cells (i.e., the MAC-T cells overexpressing GHR, or MAC-T-GHR cells) were split and seeded in 96-well plates at 1 × 10 4 cells/well.…”

Associations between newly discovered polymorphisms in the Bos taurusgrowth hormone receptor gene and performance traits in Holstein-Friesian dairy cattle

“…The action of GH is mediated by the transmembrane GH receptor (GHR), which comprises a 24‐amino acid single transmembrane domain, an extracellular binding domain and a long cytoplasmic domain (Kopchick & Andry 2000). Binding of GH to GHR activates an intracellular signalling pathway (Zhou & Jiang 2006) that induces the transcription of many genes including the insulin like growth factor‐1 (IGF‐1) gene (Jiang et al. 2007).…”