Effect of angiogenesis inhibitors on oestrogen-mediated endometrial endothelial cell proliferation in the ovariectomized mouse
| Autor: | Kenneth Lipson, Bam Bang Heryanto, Peter Rogers |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Vascular Endothelial Growth Factor A
Embryology medicine.medical_specialty Platelet-derived growth factor Indoles Angiogenesis Ovariectomy Angiogenesis Inhibitors Mice Inbred Strains Endothelial Growth Factors Fibroblast growth factor chemistry.chemical_compound Endometrium Mice Endocrinology Internal medicine medicine Animals Pyrroles Receptor Fibroblast Growth Factor Type 1 Progesterone Platelet-Derived Growth Factor Lymphokines biology Vascular Endothelial Growth Factors Immune Sera Obstetrics and Gynecology Receptor Protein-Tyrosine Kinases Kinase insert domain receptor Estrogens Cell Biology Receptors Fibroblast Growth Factor Vascular Endothelial Growth Factor Receptor-2 Angiogenesis inhibitor Vascular endothelial growth factor Fibroblast Growth Factors Vascular endothelial growth factor A Reproductive Medicine chemistry biology.protein Intercellular Signaling Peptides and Proteins Female Endothelium Vascular Platelet-derived growth factor receptor Cell Division |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1470-1626 |
| Popis: | It has been suggested that endometrial angiogenesis in response to the sex steroids oestrogen and progesterone is mediated at a local level via compounds such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF), acting through their respective tyrosine kinase receptors. The aim of the present study was to use SUGEN tyrosine kinase receptor angiogenic inhibitor compounds SU5416, SU5402, SU11652 and SU11685, to determine whether VEGF, FGF or PDGF play a role in mediating endometrial endothelial cell proliferation after administration of oestrogen and progesterone. Endometrial endothelial cell proliferation was induced in adult ovariectomized mice by either oestrogen alone for 24 h (E1), or a regimen using oestrogen alone, then progesterone with low dose oestrogen, followed by progesterone with high-dose oestrogen (PE) over a total of 7 days. Each angiogenesis inhibitor compound was injected daily for 4 days (100 mg kg(-1) day(-1), s.c.) before endometrial tissue collection at either the E1 or PE stage. This study also evaluated the effect of VEGF antiserum (0.2 ml, i.p.) on endothelial cell proliferation at the E1 stage. All four angiogenic inhibitor compounds significantly reduced endothelial cell proliferation activity at the E1 and PE stages. The greatest reduction in the endothelial cell proliferative index was at the E1 stage in the group treated with the VEGF receptor inhibitor SU5416 (2.5 +/- 0.7% versus 27.9 +/- 1.1%, P < 0.001), with a reduction of similar magnitude in the group treated with anti-VEGF antibody. At the PE stage, all four inhibitors significantly reduced endothelial cell proliferation to a similar extent, indicating that VEGF, FGF and PDGF are all involved. These results demonstrate that endometrial angiogenesis after acute oestrogen treatment is primarily mediated by VEGF, but that under the influence of combined oestrogen and progesterone, FGF and PDGF are also probably involved. |
| Databáze: | OpenAIRE |
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