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

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.