HEREGULIN INDUCES IN-VIVO PROLIFERATION AND DIFFERENTIATION OF MAMMARY EPITHELIUM INTO SECRETORY LOBULOALVEOLI

Mammary gland development and differentiation is mediated through the combined activities of systemic hormones and locally synthesized growt h factors. To determine the in vivo response of mammary epithelium to heregulin (HRG), we implanted Elvax pellets containing HRG alpha or HR G beta within the mammary glands of prepubescent female mice in the pr esence or absence of exogenous estradiol and progesterone (E/P), Mice treated in the same way with transforming growth factor alpha (TGF-alp ha) were included as a positive control. Each growth factor treatment induced epithelial ductal branching in the presence or absence of E/P, In the absence of E/P, HRG beta did not affect terminal end bud forma tion, mammary epithelium branching, or ductal migration, In contrast, TGF-alpha and HRG alpha induced ductal branching and HRG alpha induced ductal migration in the absence of E/P. The overall mammary response to growth factors was potentiated by the concomitant presence of E/P, In every case, the in vivo mammary epithelial responses to HRG alpha w ere more robust than TGF-alpha, Limited lobuloalveolar development was also observed in growth factor-treated mammary glands when E/P was pr esent, Histological examination of growth factor-induced lobuloalveoli revealed secretory products within the lumen of HRG alpha and HRG bet a lobuloalveoli. TGF-alpha-induced lobuloalveoli lacked similar secret ory products.