Developmental Changes in Insulin-like Growth Factor I Receptor Gene Expression in the Mouse Mammary Gland

The insulin-like growth factor I receptor (IGF-IR), which mediates the mitogenic action of IGF-I, has been shown to play an essential role in normal growth and development. However, the precise role of IGF-IR in the growth and differentiation of the mammary gland has not been elucidated. This study examines the profile of the IGF-IR gene and protein expression during normal postnatal mammary gland development in order to gain further insight into the role of the IGF-I IGF-IR during mammary gland morphogenesis. Gene and protein expression were examined in developing mouse mammary glands (virgin, pregnant, lactating, involuting) by real time PCR analysis and Western blotting. Both IGF-IR gene and protein expression levels were high during early pregnancy. Interestingly, the level of gene expression was significantly down-regulated during late pregnancy (5.4 fold) and lactation (9-13 fold) and significantly up-regulated (3.9 fold) during late involution, to the level observed in the virgin mammary gland. By in situ hybridization, the IGF-IR transcripts were localized to the proliferating ductal epithelium of the mammary glands of virgin mice and to the differentiating ductal and alveolar epithelium of the mammary glands during pregnancy and lactation. In the involuting gland, the transcripts were localized to the regressing ductal epithelium. These data are direct evidence that IGF-IR expression is important for alveolar cell proliferation and suggest that the progression of involution may require the down-regulation of IGF-IR gene expression. Altogether, these results demonstrate that a developmental IGF-IR gene expression pattern exists in the mouse mammary gland and that increases in gene expression at specific phases of development may reflect an important role for IGF-I IGF-IR at those phases of development.