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Dairy Science Department, University of Wisconsin, Madison, Wisconsin 53706
Address all correspondence and requests for reprints to: Dr. Lewis G. Sheffield, Dairy Science Department, University of Wisconsin, 1675 Observatory Drive, Madison, Wisconsin 53706.
Mammary tissue from midpregnant heifers was cultured with epidermal
growth factor (EGF) or transforming growth factor
for 13
days. After 1 day, 10 nM EGF or transforming growth factor
doubled DNA synthesis, whereas lower concentrations (0.1 or 1
nM) increased DNA synthesis 2- to 3-fold after 23 days in
culture. In other studies, bovine mammary tissue was transplanted to
ovariectomized athymic mice and treated for 10 days with saline,
estradiol (1 µg/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 µg/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.
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