The effects of milking frequency on insulin-like growth factor I signaling within the mammary gland of dairy cows

In dairy cows, short-term changes of milking frequency (MF) in early lactation have been shown to produce both an immediate as well as a long-term effect on milk yield. The effect of MF on milk yield is controlled locally within mammary glands and could be a function of changes in either secretory mammary epithelial cell (MEC) number or their activity. Insulin-like growth factor I (IGF-I) signaling is one candidate factor that could mediate these effects, as it can be controlled locally within mammary glands and can effect both MEC number and activity by activating the phosphoinositide 3-kinase (PI3K)/Akt and extracellular-signal-regulated kinase (ERK)1/2 pathways. To investigate the relationship between MF and IGF-I signaling, udder halves of 17 dairy cows were milked either four times a day (4x) or once a day (1x) for 14 days in early lactation. On day 14 between 3 and 5 h following milking, mammary biopsies were obtained from 10 cows from both udder halves and changes in the expression of genes associated with IGF-I signaling and the activation of the PI3K/Akt and ERK1/2 pathways were measured. The mRNA abundance of IGF type I receptor, IGF binding protein (IGFBP)-3 and IGFBP-5 were lower following 4x milking relative to 1x milking. However, the mRNA abundance of IGF-I was not effected by MF. Both IGFBP3 and IGFBP5 are thought to inhibit IGF-I, so the decrease in their mRNA abundance may serve to stimulate the IGF-I signal in the 4x-milked mammary gland. The activation of PI3K/Akt pathway was lower in response to 4x milking relative to 1x, and the activation of the ERK1/2 was unaffected by MF, suggesting they do not mediate the effects of MF.