PHYSIOLOGY AND ENDOCRINOLOGY SYMPOSIUM: Effects of insulin on mammary gland differentiation during pregnancy and lactation.

Differentiation of the mammary gland during pregnancy and the first several days following parturition is required for the establishment of a normal lactation. The expansion and development of the secretory compartment into lobuloalveloar structures that secrete milk is a complex process that is under the tight control of an array of hormones and growth factors that interact at multiple levels. Of the many factors that are required to orchestrate functional differentiation during pregnancy, insulin is often overlooked. This is likely related to the difficulty in manipulating insulin without disrupting its widespread systemic effects on metabolism. In addition, crosstalk with the IGF type 1 receptor (IGF-1R) and activation of similar downstream signaling pathways through the insulin receptor (IR) and IGF-1R often make it difficult to specifically link biological outcomes to insulin. The objective of this review is to summarize the available data that address a role for insulin in secretory differentiation of the mammary gland. Much of these data focus on a role for insulin in milk protein synthesis. However, data using conditional knockout of the IR in the mammary epithelium during mid pregnancy as well as transcriptomic approaches are discussed to present an expanded understanding of a role for insulin in functional differentiation that includes both transcriptional and post-transcriptional regulation of multiple genes involved in the process.