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

TLDR

The authors profiled EGF and TGF‑α mRNA by primer‑directed amplification across virgin, pregnant, and lactating stages and demonstrated that implantation of EGF or TGF‑α pellets into regressed, ovariectomized glands re‑initiated end‑bud formation, confirming a steroid‑independent, receptor‑mediated growth pathway. EGF and TGF‑α transcripts were present in virgin and pregnant glands but only EGF was detected in 10‑day lactating tissue; immunolocalization showed distinct spatial patterns, and either ligand alone could stimulate normal ductal growth, indicating that the two polypeptides play separate, essential roles in mammary morphogenesis.

Abstract

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.