Progesterone Withdrawal Up-Regulates Vascular Endothelial Growth Factor Receptor Type 2 in the Superficial Zone Stroma of the Human and Macaque Endometrium: Potential Relevance to Menstruation
Abstract
Several reports indicate that vascular endothelial growth factor (VEGF) expression is increased in endometrial glands and stroma during the menstrual phase in the human endometrium. Here we report that VEGF receptor type 2 (KDR), normally expressed only in the vascular endothelium, was dramatically up-regulated in the stromal cells of the superficial endometrial zones during the premenstrual phase in both human and macaque endometrium. This increase was detectable by Northern analysis, in situ hybridization, and immunocytochemistry and was cell specific, zone specific, cycle phase specific, and VEGF receptor type specific. That is, it only occurred during the premenstrual/menstrual phase, did not occur in glandular epithelium, endothelium, or stromal cells of the deepest endometrial zones, and was not observed for VEGF receptor type 1. The upregulation of stromal KDR was induced by progesterone (P) withdrawal in both women and macaques, and adding back P 24 h after P withdrawal in macaques blocked stromal, but not vascular, endothelial KDR expression. Promatrix metalloproteinase-1 (MMP-1) was coordinately up-regulated in the same stromal cell population by P withdrawal. Because of reports that VEGF can enhance MMP expression, we hypothesize that VEGF-KDR interactions may influence MMP expression in the superficial zones of the primate endometrium during the premenstrual phase, and that these interactions play a role in the induction of menstruation.
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VEGF and its receptor VEGFR-2/KDR are markedly up-regulated in superficial endometrial stromal cells in human and non-human primate models.
“VEGF and its receptor VEGFR-2 kinase insert domain receptor (KDR) are markedly up-regulated in superficial endometrial stromal cells in human and non-human primate models”
From Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications (2011) · cites this paper as Nayak et al., 2000
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- Authors
- Nayak, N. R.
- Affiliations
- Oregon National Primate Research Center (US)
- ORCID
- Nayak, N. R.
- Venue
- Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2000-09-01
- Volume
- 85
- Issue
- 9
- Pages
- 3442-3452
- ISSN
- 0021-972X (ISSN-L)
- OpenAlex
- W2070456737
- Cited by
- 66
- References
- 0
- Citations by year
- 2024: 2 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 2 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 1
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Funders
- U.S. Public Health Service (U5418185)
- National Center for Research Resources (RR-00163.)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD19182, R01HD019182)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Menstrual Health and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- progesterone withdrawal, KDR, endometrial stroma, menstruation, premenstrual phase, MMP-1, vascular endothelial growth factor, human endometrium, menstrual cycle
- MeSH terms
- Adult, Animals, Antibody Specificity, Endometrium, Female, Humans, Immunohistochemistry, Macaca mulatta, Menstruation, Progesterone, Proto-Oncogene Proteins, RNA, Messenger, Steroids, Substance Withdrawal Syndrome, Blotting, Northern, Cell Hypoxia, Up-Regulation, Stromal Cells, In Situ Hybridization, Receptors, Growth Factor, Reverse Transcriptase Polymerase Chain Reaction, Receptor Protein-Tyrosine Kinases, Receptors, Vascular Endothelial Growth Factor, Vascular Endothelial Growth Factor Receptor-1
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