PHILADELPHIA — The hormone prolactin is produced by the pituitary gland in the brain and then travels via the bloodstream to cells throughout the body, where it exerts multiple reproductive and metabolic effects, most notably on the breast where it is the master regulator of lactation. In recent years researchers have found that prolactin is also produced by some tissues outside the brain, however little is known about the functions of extra-pituitary prolactin or how its production is regulated in these tissues.

Now, the laboratory of Lewis A. Chodosh, MD, PhD, chair of the Department of Cancer Biology at the Perelman School of Medicine, University of Pennsylvania, reports in Genes & Development that activation of the PI3K-Akt oncogenic signaling pathway in the mammary glands of mice rapidly induces cells in the breast itself to produce prolactin. This, in turn, triggers Stat5 activation, mammary epithelial differentiation and milk production in virgin mice within a matter of hours.

“Remarkably, these changes occur in the absence of any of the complex hormonal changes or developmental programs that normally accompany pregnancy” explains Chodosh.

Consistent with a physiological role for prolactin outside of the brain, the Penn team found that mice bearing mutant Akt genes fail to activate Stat5 or initiate lactation when they give birth due to an inability to synthesize and secrete prolactin in the mammary gland, despite normal levels of circulating prolactin in the blood.    

These findings provide the first demonstration that the synthesis and secretion of mammary gland prolactin is regulated by PI3K-Akt signaling and identify a physiological function for extra-pituitary prolactin during a critical developmental stage that is essential for the survival of mammalian offspring.

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