TGF-BETA SUPPRESSES CASEIN SYNTHESIS IN MOUSE MAMMARY EXPLANTS AND MAY PLAY A ROLE IN CONTROLLING MILK LEVELS DURING PREGNANCY

Mammary explants from 14-15-d-pregnant mice synthesize and secrete milk proteins in culture in response to insulin, hydrocortisone, and prolactin. Here we demonstrate that transforming growth factor beta (TGFbeta) treatment suppresses, in a dose dependent and reversible manner, the ability of explants to synthesize and secrete milk caseins. TGFbeta does not affect the level of casein mRNA within explants but inhibits casein synthesis posttranscriptionally. We also show increased expression of TGFbeta2 and TGFbeta3 in intact mammary gland as pregnancy progresses, with reduced expression of all three TGFbetas at the onset of lactation. These findings suggest that endogenously produced TGFbeta may limit the accumulation of milk caseins that are produced in the mammary gland during pregnancy.