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

Nihar R. Nayak, Hilary O D Critchley, Ov Slayden, Andreas Menrad, Kristof Chwalisz, David T. Baird, Robert M. Brenner

    Research output: Contribution to journalArticle

    55 Citations (Scopus)

    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 up-regulation 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.

    Original languageEnglish (US)
    Pages (from-to)3442-3452
    Number of pages11
    JournalJournal of Clinical Endocrinology and Metabolism
    Volume85
    Issue number9
    StatePublished - 2000

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    Vascular Endothelial Growth Factor Receptor-2
    Menstruation
    Macaca
    Stromal Cells
    Endometrium
    Vascular Endothelial Growth Factor A
    Progesterone
    Up-Regulation
    Matrix Metalloproteinases
    Vascular Endothelial Growth Factor Receptor-1
    Matrix Metalloproteinase 1
    Vascular Endothelial Growth Factor Receptor
    Vascular Endothelium
    Primates
    Endothelium
    In Situ Hybridization
    Blood Vessels
    Epithelium
    Immunohistochemistry
    Cells

    ASJC Scopus subject areas

    • Biochemistry
    • Endocrinology, Diabetes and Metabolism

    Cite this

    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. / Nayak, Nihar R.; Critchley, Hilary O D; Slayden, Ov; Menrad, Andreas; Chwalisz, Kristof; Baird, David T.; Brenner, Robert M.

    In: Journal of Clinical Endocrinology and Metabolism, Vol. 85, No. 9, 2000, p. 3442-3452.

    Research output: Contribution to journalArticle

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