Hormonal Regulation of Epidermal Growth Factor Receptor Content and Signaling in Bovine Mammary Tissue**This work was supported by the University of Wisconsin College of Agricultural and Life Sciences, United States Department of Agriculture Hatch project WIS 3769, and NIH Grant HD-24094.

Abstract

Mammary tissue from midpregnant heifers was cultured with epidermal growth factor (EGF) or transforming growth factor alpha for 1-3 days. After 1 day, 10 nM EGF or transforming growth factor alpha doubled DNA synthesis, whereas lower concentrations (0.1 or 1 nM) increased DNA synthesis 2- to 3-fold after 2-3 days in culture. In other studies, bovine mammary tissue was transplanted to ovariectomized athymic mice and treated for 10 days with saline, estradiol (1 microg/day), progesterone (1 mg/day), or estradiol + progesterone. Subsequent explant culture of the bovine tissue indicated that estradiol + progesterone augmented the 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 microg/day), PRL (1 mg/day), or hydrocortisone + PRL. Hydrocortisone and PRL alone decreased, and PRL + hydrocortisone eliminated, EGF-induced DNA synthesis. EGF receptor content was unaffected by hydrocortisone but was reduced by PRL or hydrocortisone + PRL. Furthermore, the ability of EGF to induce tyrosine kinase activity was decreased by PRL and by hydrocortisone + PRL. The decreased kinase activity was greater than the decrease in receptor binding, suggesting a specific modulation of EGF receptor kinase activity in response to lactogenic hormones.

ERBB Receptors and Their Ligands in the Developing Mammary Glands of Different Species: Fifteen Characters in Search of an Author

“…In vivo LA growth [ 48 , 121 , 147 , 152 , 199 , 200 ] Mammary growth. In vitro-vivo DNA synthesis [ 143 , 160 ] EREG expression mRNA [ 9 ] function HBEGF expression mRNA [ 9 ] function TGFα expression mRNA (decreasing) [ 9 , 47 ] mRNA, protein (MEC, stroma) [ 62 , 198 ] Protein (cow) [ 72 , 73 ] mRNA [ 62 ] …”

“…In vitro-vivo DNA synthesis [ 143 , 160 ] EREG expression mRNA [ 9 ] function HBEGF expression mRNA [ 9 ] function TGFα expression mRNA (decreasing) [ 9 , 47 ] mRNA, protein (MEC, stroma) [ 62 , 198 ] Protein (cow) [ 72 , 73 ] mRNA [ 62 ] function LA growth [ 48 , 200 ] Mammary growth. In vitro-vivo DNA synthesis [ 143 , …”

“…Both TGFα and EGF are mitogenic for cultured MEC from pregnant cows [ 73 ]. Likewise, treating explants from midpregnant Holstein heifers with EGF or TGFα was sufficient to induce maximal DNA synthesis, despite suboptimal activation of ERBB1 [ 160 ]. In a similar way, MEC from pregnant ewes initiated DNA synthesis in response to EGF, TGFα, or AREG; what is more, TGFα compensated for the inhibition of DNA-synthesis induced by heparin.…”

“…In this model, PRL and HC, alone or synergistically, decreased EGF-dependent DNA-synthesis by affecting both abundance and kinase activity of ERBB1. An intriguing question that warrants investigation is whether PRL can simultaneously synergize with EGF to induce epithelial differentiation in the mammary glands of ruminants, as proposed in rodents [160][161][162].…”