title: Hormonal regulation of epidermal growth factor receptor content and signaling in bovine mammary tissue.
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.
authors.affiliation: Dairy Science Department, University of Wisconsin, Madison 53706, USA. lgsheffi@facstaff.wisc.edu
authors.forename: L G
authors.initials: LG
authors.lastname: Sheffield
mesh_terms: D000818:Animals; D002417:Cattle; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D066246:ErbB Receptors / Q000096:biosynthesis*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006728:Hormones / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009924:Organ Culture Techniques; D011233:Precipitin Tests; D011388:Prolactin / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D006728:Hormones; D004958:Estradiol; D011388:Prolactin; D004247:DNA; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D006854:Hydrocortisone