The insulin-like growth factor and epidermal growth factor families in mammary cell growth in ruminants: action and interaction with hormones.

Selective breeding and improved management have had major effects in increasing peak milk yields but relatively little effect on lactation persistency. In ruminants, cell loss appears to be largely responsible for the decline in milk yield. Little is known about the longevity of individual cells, but, in lactating dairy cows, few epithelial cells are in the S phase (DNA synthesis) of the cell cycle. The IGF and epidermal growth factor families are direct mitogens, stimulating DNA synthesis in cultures of ruminant mammary epithelial cells. Receptors that mediate the effects of these growth factors, the type 1 IGF receptor and the epidermal growth factor receptor, respectively, are present at similar levels in membranes prepared from the mammary glands of nonpregnant and pregnant sheep. Binding capacity falls by parturition and remains low during lactation. These findings suggest that the drive to mammary development in pregnancy comes from control of growth factors, and, in the case of IGF, modulating binding proteins, a control exerted by hormones, which, in general, are not themselves mitogens. A paracrine or autocrine mode of action and, therefore, local growth factor synthesis, are more likely to be important than systemic concentrations of growth factor. Stimulatory growth factors produced locally by the mammary gland include IGF-I, IGF-II, transforming growth factor-alpha, and amphiregulin. More information is needed on the control of stimulatory and inhibitory growth factors and on how growth factors control the cell cycle. Knowledge of these processes could result in strategies to improve lactation persistency by increasing secretory cell renewal or reducing cell loss during lactation.