Heparin-binding epidermal growth factor-like growth factor is differentially regulated by progesterone and estradiol in rat uterine epithelial and stromal cells.
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) cDNA was isolated from a subtracted cDNA library that selected for progesterone-induced transcripts from rat uterine stromal cells. In this study, the effects of progesterone and estradiol on the expression of HB-EGF in mature rat uterine epithelial and stromal cells have been examined. RNase protection assays and in situ hybridization demonstrated that progesterone stimulated expression of HB-EGF in rat uterine stromal cells, but repressed levels of HB-EGF mRNA in luminal and glandular epithelial cells. In contrast, estradiol treatment strongly enhanced HB-EGF expression in epithelial cells, but had no effect on mRNA levels for this growth factor in stromal cells. Progesterone treatment followed by estradiol injection stimulated HB-EGF expression in stromal cells and repressed expression in luminal and glandular epithelium. Stimulation of HB-EGF expression in stromal cells by progesterone was not inhibited by treatment with cycloheximide, demonstrating that HB-EGF mRNA expression is a primary response of stromal cells to progesterone. These results reveal that expression of HB-EGF is stimulated in epithelial and stromal cells in vivo under the same hormonal conditions that induce cell proliferation in each of these cell types and strongly suggest that HB-EGF may mediate the mitogenic effects of steroid hormones in the rat uterus.
Zhang
Z
Z
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
Funk
C
C
Roy
D
D
Glasser
S
S
Mulholland
J
J
D000818:Animals; D004815:Epidermal Growth Factor / Q000032:analysis / Q000235:genetics*; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006493:Heparin / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000502:physiology; D014599:Uterus / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*
C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011374:Progesterone; D004958:Estradiol; D004815:Epidermal Growth Factor; D006493:Heparin