Local IGF-I Axis in Peripubertal Ruminant Mammary Development

The regulation of mammary growth and development in heifers is accomplished by complexinteractions of hormones, growth factors, and extracellular matrix molecules. Many of thesegrowth stimulators are believed to be locally produced in the mammary gland and to beaffected by developmental and nutritional status. Although estrogen and growth hormone areconsidered critical to pubertal mammogenesis, results summarized in this review suggest thatIGF-I⁶ and IGF binding proteins are especially important locally-produced growth regulatorsin peripubertal ruminants. This assertion is supported by studies of ovariectomized heifers, inwhich increased stromal IGFBP-3 and reduced IGF-I correspond with a failure of udderdevelopment. Similarly, reduced mammary development with overfeeding coincides withreduced mitogenic activity of mammary tissue extracts and altered concentrations of IGF-Iand IGFBPs. In vitro studies convincingly demonstrate that much of the mitogenic activity ofmammary extracts or serum can be attributed to IGF-I and that alterations in IGFBP-3 modulateits effectiveness. Thus by analogy to second messenger mechanisms of action for proteinhormones, local mammary-derived growth factors likely explain many of the effects attributedto the classic mammogenic hormones.