Expression and functional properties of transforming growth factor alpha and epidermal growth factor during mouse mammary gland ductal morphogenesis.

Primer-directed enzyme amplification was used to examine epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) mRNA transcripts in mammary glands of young virgin, mature virgin, midpregnant, and midlactating mice. Transcripts for both EGF and TGF-alpha mRNA were detected in virgin and pregnant mice, whereas transcripts for EGF mRNA but not TGF-alpha mRNA were expressed in 10-day lactating mice. TGF-alpha 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-alpha into the regressed mammary gland of ovariectomized mice stimulated the reappearance of end buds; contralateral glands implanted with pellets containing 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-alpha is sufficient to stimulate the pattern of normal ductal growth. The detection of EGF and TFF-alpha transcripts at different stages of mammary gland development and the different patterns of immunolocalization suggest that each polypeptide plays a different role in normal mammary gland morphogenesis.