Local IGF-I axis in peripubertal ruminant mammary development

The regulation of mammary growth and development in heifers is accomplished by complex interactions of hormones, growth factors, and extracellular matrix molecules. Many of these growth stimulators are believed to be locally produced in the mammary gland and to be affected by developmental and nutritional status. Although estrogen and growth hormone are considered critical to pubertal mammogenesis, results summarized in this review suggest that IGF-I-6 and IGF binding proteins are especially important locally-produced growth regulators in peripubertal ruminants. This assertion is supported by studies of ovariectomized heifers, in which increased stromal IGFBP-3 and reduced IGF-I correspond with a failure of udder development. Similarly, reduced mammary development with overfeeding coincides with reduced mitogenic activity of mammary tissue extracts and altered concentrations of IGF-I and IGFBPs. In vitro studies convincingly demonstrate that much of the mitogenic activity of mammary extracts or serum can be attributed to IGF-I and that alterations in IGFBP-3 modulate its effectiveness. Thus by analogy to second messenger mechanisms of action for protein hormones, focal mammary-derived growth factors likely explain many of the effects attributed to the classic mammogenic hormones.