Insulin-like growth factor (IGF) system in the bovine mammary gland and milk

Primary bovine mammary cells express the two IGF receptors (IGF-IR, IGF-IIR), insulin receptor, and four IGFBPs (IGFBP-2, -3, -4, and -5). Examination of the IGF-IR during the mammary gland lactation cycle shows that IGF-IR number declines at parturition, a change that coincides with decreases in the blood level of its ligand, IGF-I. IGF-II and IGF-IIR are largely unchanged. IGFBP-3 is the predominant mammary IGFBP and its concentration also declines in blood and milk during lactation compared to prepartum and involution periods. Time of lactation and pregnancy were the main determinants of milk but not blood IGFBP-3 levels. IGFBP-3 binds to membrane proteins of bovine mammary tissue; an IGFBP-3 binding protein has been identified as bovine lactoferrin. Lactoferrin has the capacity to compete with IGF binding to IGFBP-3. Appearance of both IGFBP-3 and lactoferrin in conditioned media of primary cultures of bovine mammary cells was stimulated by all trans retinoic acid (atRA). Furthermore, atRA was necessary for the entry of exogenously added lactoferrin into the mammary cell nucleus, while IGFBP-3 entry into the nuclei of atRA treated cells required the presence of lactoferrin. These findings reveal a novel role for lactoferrin, suggesting that lactoferrin is critically involved in the regulation of the IGF system during the involution period.