Endocrine and paracrine regulation of endometrial angiogenesis.
The human endometrium is a complex tissue comprised of different cell types, including epithelial, stromal, inflammatory, perivascular, and blood vessel cells. The hormonal receptivity and distribution of these cell populations change during the menstrual cycle. Cyclical endometrial growth is dependent on its ability to regenerate a vascular capillary network, which grows in parallel with the proliferation and differentiation of the endometrial lining. Natural hormonal effects on the endometrium and endocrine manipulation of this tissue, in response to the use of exogenous steroid therapies, can affect endometrial capillary proliferation and function, leading to clinical abnormalities of uterine bleeding. We propose that the regulation of endometrial angiogenesis is mediated indirectly via complex interactions among cell types. Our laboratory has focused on a prototypical member of the angiogenic proteins, vascular endothelial growth factor (VEGF)-A. In this paper we present data demonstrating that VEGF-A expression in normal endometrial epithelial and stromal cells and in Ishikawa adenocarcinoma cells is increased by an ovarian steroid, estradiol. Infiltrating immune cells, particularly polymorphonuclear granulocytes, also are sources of VEGF-A. In inflammatory conditions involving the endometrium (e.g., endometriosis), a proinflammatory cytokine, IL-1beta, can mediate neoangiogenesis by inducing VEGF-A gene transcription. Thus, endometrial vascularization is effected by both endocrine and paracrine pathways.
Taylor
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RN
Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco 94143-0556, USA. rtaylor@socrates.ucsf.edu
Lebovic
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DI
Hornung
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D
Mueller
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MD
D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004703:Endocrine System / Q000502:physiology*; D004717:Endometrium / Q000098:blood supply* / Q000166:cytology; D016228:Endothelial Growth Factors / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019899:Paracrine Communication / Q000502:physiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013256:Steroids / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016207:Cytokines; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D013256:Steroids; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors