Role of IGF-I in normal mammary development.

Growth hormone (GH) is now believed to be the pituitary factor that is responsible for mammary ductal morphogenesis. Mammary development at puberty occurs because of synergy between GH and estrogen on formation of terminal end buds (TEBs). TEBs extend into the substance of the mammary gland fat pad, resulting in ductal morphogenesis. Ultimately, the whole mammary fat pad accommodates a complex network of ducts. IGF-I or des(1-3) IGF-I mimic the actions of GH on TEB formation in hypophysectomized, gonadectomized rats. Since GH stimulates IGF-I mRNA within the mammary gland synergistically, we hypothesize that IGF-I partially mediates actions of GH in mammary gland development. Studies in transgenic mice overexpressing IGF-I, des(1-3) IGF-I, or IGFBP-3 show that IGF-I causes ductal hypertrophy in the lactating mouse and prevention of post-lactational mammary gland involution. One of the mechanisms for this effect involves apoptosis. The potential role of GH or IGF-I in mammary carcinogenesis, and the applicability of animal studies to humans, are discussed.