Potential roles for the insulin-like growth factor binding proteins during development of the mouse mammary gland

Mammary gland development is an intricate and complex process that is influenced by many factors.; The bioavailability and bioactivity of IGF-I and IGF-II can be regulated by the insulin-like growth factor binding proteins. This family of six high-affinity binding proteins are synthesized in certain developing tissues, including the mammary gland, and function to regulate IGF bioavailability and transport during normal everyday life.; To investigate the normal expression of the IGFBPs during mammary development, we have examined the expression of the IGFBP mRNAs and protein during postnatal mammary development. Results from this study provide specific cellular localization of the IGFBPs and correlation of these expression patterns with precise developmental time points. These data substantiate a role for the IGFBPs as autocrine/paracrine factors that can influence IGF-mediated mammary gland growth.; IGFBP expression during pregnancy, lactation and involution was also investigated. Each IGFBP exhibited a unique pattern of expression that could be localized to either the epithelial or stromal compartments. IGFBP-5 was the most abundant IGFBP at each developmental stage. IGFBP-5 mRNA was localized to the epithelial compartment. Alternatively, expression for IGFBP-5 and IGFBP-2 protein was found to be the least abundant during lactation and early involution. IGFBP-3 mRNA was located in the outer layer of the ductal structures during pregnancy but at the later stages of lactation and involution the message became diffuse throughout the epithelial compartment. Both IGFBP-2 and IGFBP-4 mRNA were distributed throughout the stromal compartment. Interestingly, the presence of a large quantity of mRNA message for a particular binding protein did not always reflect the presence of excess protein.; Lastly, ductal development was analyzed in a mouse line that was overexpressing IGFBP-5. At five weeks of age, no significant differences were seen in the ductal tree progression. However, at later ages, 12 and 31 weeks, significant deficits were seen in the ductal tree. A testable hypothesis is that the excess IGFBP-5 binds the IGFs and prevents them from interacting with the IGF-IR, which results in retarded or incomplete development of the mammary gland.; The data presented in this study supports the concept of compartmentalization of the IGFBPs. Localized expression of the IGFBPs to either the stromal or epithelial tissues during distinct times of mammary development may help direct and control IGF-mediated growth. (Abstract shortened by UMI.)...