Mediators of estradiol-stimulated mitosis in the rat uterine luminal epithelium.
The effects of estradiol treatment, which stimulates cell division in rat uterine epithelial cells, on the in vivo expression of heparin-binding epidermal growth factor (HB-EGF), cyclin D1, and cyclin B1 messenger RNA (mRNA) in these cells have been examined using ribonuclease protection assays. Estradiol gave rise to significant increases in steady state levels of HB-EGF 2 and 24 h after treatment. Cyclin D1 mRNA levels were elevated 8 and 10 h after estradiol administration, corresponding to the G1 phase of the mitotic cycle, and cyclin B1 mRNA was only expressed 16-24 h after estradiol treatment, which corresponds to the G2 and M phases of the rat uterine epithelial cell cycle. Estradiol-stimulated increases in HB-EGF mRNA were not affected by treatment with cycloheximide, but were inhibited by the estrogen antagonist compound, ICI 164,384, demonstrating that the estrogen-stimulated increase in HB-EGF mRNA is a primary, estrogen receptor-mediated response of rat uterine epithelium to estradiol. Progesterone treatment, which blocks epithelial cells in G1 of the cycle, suppressed levels of HB-EGF mRNA below those observed in ovariectomized rats. These results indicate that HB-EGF mediates the regulatory effects of both estradiol and progesterone on rat uterine epithelial cell proliferation through an effect on the production of G1 phase molecules such as cyclin D1.
Zhang
Z
Z
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Laping
J
J
Glasser
S
S
Day
P
P
Mulholland
J
J
D000818:Animals; D019926:Cyclin B / Q000235:genetics; D056744:Cyclin B1; D019938:Cyclin D1 / Q000235:genetics; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000235:genetics / Q000502:physiology*; D004848:Epithelium / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008938:Mitosis / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000166:cytology / Q000187:drug effects*
C534701:Ccnb1 protein, rat; D019926:Cyclin B; D056744:Cyclin B1; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D019938:Cyclin D1; D004958:Estradiol; D004815:Epidermal Growth Factor; D004247:DNA