Role of the insulin-like growth factors and their binding proteins in lactation

Insulin-like growth factor (IGF)-I is thought to mediate a portion of the effects of bST on lactation in dairy cows. Serum concentrations of IGF-I are increased in lactating cows that were treated with bST, and IGF-I receptors are present in bovine mammary tissue. In addition, close arterial infusion of IGF-I into the mammary gland of goats increases milk yield. Little evidence exists to support a direct galactopoietic effect of IGF-I in ruminants. However, IGF-I is a potent mitogen for mammary epithelial cells and may also influence the inhibition of apoptosis of this cell type. The IGF are found in association with a family of individual binding proteins. The high affinity of the IGF for these proteins relative to the IGF receptor allows them to modulate IGF-I bioactivity in the mammary gland at the cellular level. Mammary epithelial cells synthesize multiple forms of IGF binding proteins, and one of these, IGF binding protein-3, is specifically regulated by the IGF. Stimulation of DNA synthesis by IGF-I is enhanced in bovine mammary epithelial cells that overexpress the IGF binding protein-3. These data indicate that IGF-I can stimulate the synthesis of an IGF binding protein, which enhances its own mitogenic activity. However, whether this mechanism is operative in the lactating mammary gland in vivo is unknown. Given the complexity of the interactions between the IGF and their binding proteins, more information is needed before the role of these growth factors in regulating growth, differentiation, and apoptosis of mammary epithelial cells is delineated.