HORMONAL-REGULATION OF EPIDERMAL GROWTH-FACTOR RECEPTOR CONTENT AND SIGNALING IN BOVINE MAMMARY TISSUE

Mammary tissue from midpregnant heifers was cultured with epidermal gr owth factor (EGF) or transforming growth factor alpha for 1-3 days. Af ter 1 day, 10 nM EGF or transforming growth Factor alpha doubled DNA s ynthesis, whereas lower concentrations (0.1 or 1 nM) increased DNA syn thesis 2- to 3-fold after 2-3 days in culture. In other studies, bovin e mammary tissue was transplanted to ovariectomized athymic mice and t reated for 10 days with saline, estradiol (1 mu g/day), progesterone ( 1 mg/day), or estradiol + progesterone. Subsequent explant culture of the bovine tissue indicated that estradiol + progesterone augmented th e ability of EGF to stimulate DNA synthesis. The increased response to EGF was associated with increased EGF binding and with increased EGF- induced tyrosine kinase that paralleled the increased EGF binding. In other studies, athymic mice bearing xenografted bovine mammary tissue were primed for 10 days with estradiol and progesterone, followed by 2 -day treatment with saline (control), hydrocortisone (200 mu g/day), P RL (1 mg/day), or hydrocortisone + PRL. Hydrocortisone and PRL alone d ecreased, and PRL + hydrocortisone eliminated, EGF-induced DNA synthes is. EGF receptor content was unaffected by hydrocortisone but was redu ced by PRL or hydrocortisone + PRL. Furthermore, the ability of EGF to induce tyrosine kinase activity was decreased by PRL and by hydrocort isone + PRL. The decreased kinase activity was greater than the decrea se in receptor binding, suggesting a specific modulation of EGF recept or kinase activity in response to lactogenic hormones.