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 i ncreasing peak milk yields but relatively little effect on lactation p ersistency. 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 a re in the S phase (DNA synthesis) of the cell cycle. The IGF and epide rmal growth factor families are direct mitogens, stimulating DNA synth esis in cultures of ruminant mammary epithelial cells. Receptors that mediate the effects of these growth factors, the type 1 IGF receptor a nd the epidermal growth factor receptor, respectively, are present at similar levels in membranes prepared from the mammary glands of nonpre gnant and pregnant sheep. Binding capacity falls by parturition and re mains low during lactation. These findings suggest that the drive to m ammary development in pregnancy comes from control of growth factors, and, in the case of IGF, modulating binding proteins, a control exerte d by hormones, which, in general, are not themselves mitogens. A parac rine or autocrine mode of action and, therefore, local growth factor s ynthesis, 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-cy, an d amphiregulin. More information is needed on the control of stimulato ry and inhibitory growth factors and on how growth factors control the cell cycle. Knowledge of these processes could result in strategies t o improve lactation persistency by increasing secretory cell renewal o r reducing cell loss during lactation.