FUNCTIONAL RESCUE OF STAT5A-NULL MAMMARY TISSUE THROUGH THE ACTIVATION OF COMPENSATING SIGNALS INCLUDING STAT5B

Prolactin induces mammopoiesis and lactogenesis through the Janus kina se-signal transducers and activators of transcription pathway, with St at5a being a principal and obligate cytoplasmic and nuclear signaling molecule. Mice from which the Stat5a gene has been deleted fail to dev elop functional mammary tissue during their first pregnancy. Lobuloalv eolar outgrowth is curtailed, and epithelial cells fail to progress to functional differentiation, Here, we investigate whether the effect o f Stat5a deficiency is restricted to the epithelium and whether the gl and has the capacity to activate alternative signaling pathways that c ould restore development and function. Mammary gland transplant experi ments showed that Stat5a-deficient epithelium does not differentiate i n wild-type stroma, thus demonstrating a cell-autonomous role for Stat 5a. The capacity of Stat5a-deficient mammary tissue to develop and sec rete milk was measured after consecutive pregnancies and with postpart um suckling. Neither of these regimens could independently restore lac tation. However, the combination of several pregnancies and suckling s timuli resulted in a partial establishment of lactation and an increas e of Stat5b activity. These experiments demonstrate that the mammary g land has inherent plasticity that allows it to use different signals t o achieve its ultimate purpose, the production of milk to nurture newb orn offspring.