title: Effects of estradiol-17beta on expression of mRNA for seven angiogenic factors and their receptors in the endometrium of ovariectomized (OVX) ewes.
abstract: We have previously established an ovariectomized (OVX) ewe model to study how steroid removal and replacement affects uterine blood vessel and tissue growth. Using this model, endometrial expression of mRNA for 14 angiogenic factors (7 genes and their respective receptors) in caruncular (CAR) and intercaruncular (ICAR) endometrium were evaluated by quantitative real time RT-PCR at 0 (control), 2, 4, 8, 16, or 24 h after treating OVX ewes with an estradiol-17beta (E2) implant. In CAR and ICAR, compared to 0 h, the mRNA expression of vascular endothelial growth factor (VEGF), VEGF receptor (R)1, soluble guanylate cyclase (GUCY1B3; the R for nitric oxide [NO]), hypoxia inducible factor (HIF)1alpha, and placental growth factor (PlGF) increased by 4 h after E2-treatment, but basic fibroblast growth factor (FGF2), endothelial NO synthase (NOS3), angiopoietin (ANGPT)1, ANGPT2, ANGPT receptor Tie2 by 2 h after E2. Expression of mRNA for FGFR2 IIIc was increased at 2 h by E2-treatment in ICAR, but not in CAR. By contrast, expression of neuropilin (NP)1 mRNA was increased at 2 h in CAR, but not ICAR. The mRNA expression of VEGF, FGF2, HIF1 alpha, and PlGF was positively correlated with mRNA expression of NOS3, VEGFR1, and Tie2 suggesting some E2-stimulated interactions between these factors in promoting blood vessel growth. Thus, several major angiogenic factors and their receptors are increased within hours after E2-treatment, which indicates that E2 plays a role in regulation of angiogenesis in the uterus. By using the OVX ewe model, we may begin to understand the molecular basis of E2 effects on angiogenesis in the endometrium and, eventually, how angiogenesis is regulated in normal versus pathological conditions.
authors.affiliation: Department of Animal and Range Sciences, Cell Biology Center, North Dakota State University, Fargo, ND 58105-5727, USA. mary.lynn.johnson@ndsu.edu
authors.forename: Mary Lynn
authors.initials: ML
authors.lastname: Johnson
authors.forename: Anna T
authors.initials: AT
authors.lastname: Grazul-Bilska
authors.forename: Dale A
authors.initials: DA
authors.lastname: Redmer
authors.forename: Lawrence P
authors.initials: LP
authors.lastname: Reynolds
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism*; D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005786:Gene Expression Regulation; D006162:Guanylate Cyclase / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010052:Ovariectomy; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D042787:Receptor, TIE-2 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012044:Regression Analysis; D012756:Sheep; D000071756:Soluble Guanylyl Cyclase; D013997:Time Factors; D014599:Uterus / Q000473:pathology; D000099153:Pentraxins
chemical_list: D042501:Angiogenic Proteins; D002097:C-Reactive Protein; D004958:Estradiol; D016222:Fibroblast Growth Factor 2; D006162:Guanylate Cyclase; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009419:Nerve Tissue Proteins; D052250:Nitric Oxide Synthase Type III; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D042787:Receptor, TIE-2; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D000071756:Soluble Guanylyl Cyclase; D000099153:Pentraxins; C000605664:GUCY1B1 protein, human; C497442:HIF1A protein, human; C000608036:PGF protein, human