Expression and functional properties of transforming growth factor a and epidermal growth factor during mouse mammary gland

Primer-directed enzyme amplification was used to examine epidermal growth factor (EGF) and trans- forming growth factor a (TGF-a) mRNA transcripts in mam- mary glands of young virgin, mature virgin, midpregnant, and midlactating mice. Transcripts for both EGF and TGF-a mRNA were detected in virgin and pregnant mice, whereas transcripts for EGF mRNA but not TGF-a mRNA were expressed in 10-day lactating mice. TGF-a was localized in the epithelial cap-cell layer of the advancing terminal end bud and in the stromal fibroblasts at the base of the terminal end bud; EGF was localized in the inner layers of the terminal end bud and in ductal cells of mammary epithelium. Implantation of pellets containing EGF or TGF- a into the regressed mammary gland of ovariectomized mice stimulated the reappearance of end buds; contralateral glands implanted with pellets contain- ing albumin or insulin were not affected. These results indicate that an EGF-receptor-mediated pathway remained intact in the mammary gland epithelium in the absence of ovarian steroids and that local availability of either EGF or TGF- a is sufficient to stimulate the pattern of normal ductal growth. The detection of EGF and TGF- a transcripts at different stages of mammary gland development and the different patterns of immunolocal- ization suggest that each polypeptide plays a different role in normal mammary gland morphogenesis. C ~~~~~D