Making milk: A new link between STAT5 and Akt1.

Abstract

The transcription factor STAT5A is essential for two processes during mammary gland development. First, it controls the development of luminal progenitor cells from stem cells(1) and second, it has a role during pregnancy where it is required for alveologenesis(2) (,) (3) the production of clusters of luminal cells that synthesize and secrete milk during lactation. Thus, deletion of STAT5A in late pregnancy results in lactation failure. Alveologenesis requires the proliferation of a different lineage of luminal epithelial cells in response to the pregnancy hormones progesterone and prolactin, the latter of which activates STAT5. Prolactin is required additionally during lactation to ensure adequate milk production and the transcription of several milk protein genes has been shown to be regulated by STAT5.(4) (,) (5) On the other hand, the PI3K/Akt pathway is essential for the synthesis of other milk components such as lipids and lactose.(6) In recent elegant work from Lewis Chodosh's laboratory, published in Genes and Development, these two pathways are now shown to be directly linked.(7) More specifically, it is shown that the PI3K/Akt pathway induces autocrine prolactin production and that this is required for the initiation of lactation.