Regulation of mammary growth and function by TGF-beta.
We have previously shown that TGF-beta 1 rapidly and reversibly inhibits ductal growth in vivo when administered by miniature slow-release plastic implants. A possible role for endogenous TGF-beta 1 was suggested by the observation that the normal gland displayed substantial, developmentally regulated levels of TGF-beta 1 transcripts and protein. These studies have now been extended to include the other two mammalian TGF-beta isoforms. When tested with slow-release plastic implants, TGF-beta 2 and TGF-beta 3 also caused disappearance of the proliferating mammary stem cell layer, with rapid involution of ductal end buds and cessation of glandular growth. None of the isoforms was active in inhibiting alveolar morphogenesis. We conclude that under the conditions of these tests, the three mammalian isoforms are functionally equivalent. However, striking differences in patterns of gene expression and in the distribution of immunoreactive peptides suggest that TGF-beta 2 was expressed only at low levels, and mainly during pregnancy. TGF-beta 3 was expressed in ductal stroma and epithelium, and was the only isoform detected in myoepithelial cells. Developing alveolar tissue and its associated ducts displayed striking TGF-beta 3 gene expression and immunostaining, which were greatly reduced during lactation. We are now investigating the possibility that the observed high levels of TGF-beta expression in pregnancy, particularly of TGF-beta 3, and the absence of substantial expression of any isoform during lactation, may indicate a role for the TGF-beta in regulating functional differentiation or the onset of milk secretion.
Daniel
C W
CW
Department of Biology, University of California, Thimann Laboratories, Santa Cruz 95064.
Robinson
S D
SD
D000818:Animals; D008321:Mammary Glands, Animal / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*
D016212:Transforming Growth Factor beta