Expression of the insulin-like growth factor binding proteins during postnatal development of the murine mammary gland

IGF-I and IGF-II have known roles in postnatal development of the mammary gland. In contrast, the function of the high-affinity IGF binding proteins (IGFBPs) in mammary growth and differentiation is largely unknown. The goal of these studies was to determine the patterns and levels of IGFBP expression during postnatal growth of the murine mammary gland. IGFBP-1 to -5 proteins were detected in mammary tissue by immunoblotting during both pubertal and pregnancy-induced growth; however, the regulation of each IGFBP was distinct through these developmental periods. IGFBP-2 to -5 mRNAs were readily detectable in the developing gland by in situ hybridization analyses but were expressed in distinct cellular sites. IGFBP-3 and -5 mRNAs were expressed in the developing epithelial structures and in isolated stromal cells during ductal growth and alveolar differentiation. In the terminal end buds (TEBs), IGFBP-3 mRNA expression was consistent with its localization in the cap cells, whereas IGFBP-5 was highly expressed in the body cells of the TEB. In contrast, IGFBP-2 and -4 mRNAs were expressed predominantly in stromal cells. IGFBP-2 mRNA was localized to restricted sites in the neck of the TEB and along the ductal structures, whereas IGFBP-4 mRNA was widely expressed in the stroma surrounding the epithelial structures. Protein and mRNA expression for most of the IGFBPs decreased during lactational ages. Levels of IGFBP-2 and -5 protein increased after pup removal during forced involution. Taken together, these data suggest important functions for the family of IGFBPs during postnatal growth and differentiation of the mammary epithelium.