Adult tissue angiogenesis: evidence for negative regulation by estrogen in the uterus.
Increased uterine vascular permeability and angiogenesis are two major events of embryo implantation and placentation during pregnancy. These latter processes require coordinated, uterine-specific interactions between progesterone (P4) and estrogen (E) signaling. Although roles of these steroids have long been suspected, definitive functions of E and/or P4 in uterine angiogenesis still remain elusive. We have therefore exploited the availability of reporter and mutant mice to explore the regulation of angiogenesis in response to steroid hormonal changes in vivo. We present here molecular, genetic, physiological, and pharmacological evidence that E and P4 have different effects in vivo: E promotes uterine vascular permeability but profoundly inhibits angiogenesis, whereas P4 stimulates angiogenesis with little effect on vascular permeability. These effects of E and P4 are mediated by differential spatiotemporal expression of proangiogenic factors in the uterus.
Ma
W
W
Department of Molecular and Integrative Physiology, Ralph L. Smith Research Center, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Tan
J
J
Matsumoto
H
H
Robert
B
B
Abrahamson
D R
DR
Das
S K
SK
Dey
S K
SK
D000818:Animals; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D005260:Female; D000077267:Fulvestrant; D006727:Hormone Antagonists / Q000494:pharmacology; D008222:Lymphokines / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D015735:Mifepristone / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology*; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D014599:Uterus / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D006727:Hormone Antagonists; D008222:Lymphokines; D011960:Receptors, Estrogen; D017978:Receptors, Growth Factor; D011981:Receptors, Prolactin; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000077267:Fulvestrant; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor