Hormonal Regulation of Gonadal Angiogenesis

  • H. William Schnaper
  • Constance E. Runyan
Part of the Cardiovascular Molecular Morphogenesis book series (CARDMM)


In the reproductive system, the rapid growth and regression of decidual tissue depends on concomitant increases and decreases in the extent of the vascular network supporting that tissue. This suggests that, like reproductive organ function, angiogenesis and vessel regression are regulated by gonadal steroids. This chapter considers the evidence supporting this hypothesis and discusses potential mechanisms by which these hormones may modulate vascular cell function.


Endothelial Cell Vascular Endothelial Growth Factor Menstrual Cycle Human Umbilical Vein Endothelial Cell Corpus Luteum 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Akashita, M., Kozaki, K., Eto, M., Yoshizumi, M., Ishkawa, M., and Toba, K. 1998. Estrogen attenuates endothelin-1 production by bovine endothelial cells via estrogen receptor. Biochem. Biophys. Res. Commun. 251:17–21.CrossRefGoogle Scholar
  2. Albuquerque, M. L. C., Akiyama, S. K., and Schnaper, H. W. 1998. Human coronary artery endothelial cell secretion of basic fibroblast growth factor is enhanced by matrix proteins, 113-estradiol, and a PKC signaling pathway. Exp. Cell Res. 245:163–169.PubMedCrossRefGoogle Scholar
  3. Alvarez, R. J., Gips, S. J., Moldovan, N., Wilhide, C. C., Milliken, E. E., and Hoang, A. T. 1997. 1713-estradiol inhibits apoptosis of endothelial cells. Biochem. Biophys. Res. Commun. 237:372–381.PubMedCrossRefGoogle Scholar
  4. Aronica, S. M., Kraus, W. L., and Katzenellenbogen, B. S. 1994. Estrogen action via the cAMP signaling pathway: stimulation of adenylate cyclase, and cAMP-regulated gene transcription. Proc. Natl. Acad. Sci. USA 91:8517–8521.PubMedCrossRefGoogle Scholar
  5. Attalla, H., Mäkela, T. P., Adlercreutz, H., and Anderson, L. C. 1996. 2-Methoxyestradiol arrests cells in mitosis without depolymerizing tubulin. Biochem. Biophys. Res. Commun. 228:467–473.PubMedCrossRefGoogle Scholar
  6. Augustin, H. G., Braun, K., Telemenakis, I., Modlich, U., and Kuhn, W. 1995. Ovarian angiogenesis. Phenotypic characterization of endothelial cells in a physiological model of blood vessel growth and regression. Am. J. Pathol. 147:339–351.PubMedGoogle Scholar
  7. Bagavandoss, P., Sage, E. H., and Vernon, R. B. 1998. Secreted protein, acidic and rich in cysteine (SPARC) and thrombospondin in the developing follicle and corpus luteum of the rat. J. Histochem. Cytochem. 46:1043–1049.PubMedCrossRefGoogle Scholar
  8. Banerjee, S. K., Campbell, D. R., Weston, A. P., and Banerjee, D. K. 1997. Biphasic estrogen response on bovine adrenal medulla capillary endothelial cell adhesion, proliferation and tube formation. Mol. Cell. Biochem. 177:97–105.PubMedCrossRefGoogle Scholar
  9. Bayard, F., Clamens, S., Delsol, G., Blaes, N., Maret, A., and Faye, J. C. 1995. Oestrogen synthesis, oestrogen metabolism and functional oestrogen receptors in bovine aortic endothelial cells. Ciba Found. Symp. 191:122–132.PubMedGoogle Scholar
  10. Brinkmann, A. O., Faber, P. W., van Rooij, H. C. J., Kuiper, G. G. J. M., Ris, C., Klassen, P., van der Korput, J. A., Voorhorst, M. M., van Laar, J. H., Mulder, E., et al. 1989. The human androgen receptor: domain structure, genomic organization and regulation of expression. J. Steroid Biochem. 34:307–310.PubMedCrossRefGoogle Scholar
  11. Brodie, A., Lu, Q., and Nakamura, J. 1997. Aromatase in the normal breast and breast cancer. J. Steroid Biochem. Mol. Biol. 61:281–286.PubMedCrossRefGoogle Scholar
  12. Brooks, P. C., Montgomery, A. M., Rosenfeld, M., Reisfeld, R. A., Hu, T., Klier, G., and Cheresh, D. A. 1994. Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell 79:1157–1164.PubMedCrossRefGoogle Scholar
  13. Chen, S.-J., Li, H., Durand, J., Oparil, S., and Chen, Y.-F. 1996. Estrogen reduces myointimal proliferation after balloon injury of rat carotid artery. Circulation 93:577–584.PubMedCrossRefGoogle Scholar
  14. Chen, Z., Yuhanna, I. S., Galcheva-Gargova, Z., Karas, R. H., Mendelsohn, M. E., and Shaul, P. W. 1999. Estrogen receptor a mediates the nongenomic activation of endothelial nitric oxide synthase by estrogen. J. Clin. Invest. 104:401–406.CrossRefGoogle Scholar
  15. Cid, M. C., Esparza, J., Schnaper, H. W, et al. 2000. Estradiol enhances endothelial cell interactions with extracellular matrix proteins via an increase in integrin expression and function. Angiogenesis 3:271–280.CrossRefGoogle Scholar
  16. Collins, W., Jurkovic, D., Bourne, T., Kurjak, A., and Campbell, S. 1991. Ovarian morphology, endocrine function and intra-follicular blood flow during the peri-ovulatory period. Hum. Reprod. 6:319–324.PubMedGoogle Scholar
  17. Cryns, V., and Yuan, J. 1998. Proteases to die for. Genes Dev. 12:1551–1570.PubMedCrossRefGoogle Scholar
  18. Darkow, D. J., Lu, L., and White, R. E. 1997. Estrogen relaxation of coronary artery smooth muscle is mediated by nitric oxide and cGMP. Am. J. Physiol. 272:H2765–H2773.PubMedGoogle Scholar
  19. Diano, S., Horvath, T. L., Mor, G., Register, T., Adams, M., Harada, N., and Naftoklin, F. 1999. Aromatase and estrogen receptor immunoreactivity in the coronary arteries of monjeys and human subjects. Menopause 6:21–28.PubMedCrossRefGoogle Scholar
  20. Duffy, D. M., Wells, T. R., Haluska, G. J., and Stouffer, R. L. 1997. The ratio of progesterone receptor isoforms changes in the monkey corpus lutuem during the luteal phase of the menstrual cycle. Biol. Reprod. 57:693–699.CrossRefGoogle Scholar
  21. Ferrara, N., Chen, H., Davis-Smyth, T., Gerber, H.-P., Nguyen, T.-N., Peers, D., Chisholm, V., Hillan, K. J., and Schwall, R. H. 1998. Vascular endothelial growth factor is essential for corpus luteum angiogenesis. Nat. Med. 4:336–340.Google Scholar
  22. Folkman, J., and Haudenschild, C. 1980. Angiogenesis in vitro. Nature 288:551–556. Franck-Lissbrant, I., Häggstrom, S., Damber, J.-E., and Bergh, A. 1998. Testosterone stimulates angiogenesis and vascular regrowth in the ventral prostate in castrated adult rats. Endocrinology 139:451–456.Google Scholar
  23. Fujimoto, J., Hori, M., Ichigo, S., Morishita, S., and Tamaya, T. 1996. Estrogen activates migration potential of endometrial cancer cells through basement membrane. Tumor Biol. 17:48–57.CrossRefGoogle Scholar
  24. Fujimoto, J., Sakaguchi, H., Hirose, R., and Tamaya, T. 1999. Expression of platelet-derived endothelial cell growth factor (PD-ECGF) related to angiogenesis in ovarian endometriosis. J. Clin. Endocrinol. Metab. 84:359–362.PubMedCrossRefGoogle Scholar
  25. Furlow, J. D., Murdoch, F. E., and Gorski, J. 1993. High affinity binding of the estrogen receptor to a DNA response element does not require homodimer formation or estrogen. J. Biol. Chem. 268:12519–12525.PubMedGoogle Scholar
  26. Goede, V., Schmidt, T., Kimmina, S., Kozian, D., and Augustin, H. G. 1998. Analysis of blood vessel maturation processes during cyclic ovarian angiogenesis. Lab. Invest. 78:1385–1394.Google Scholar
  27. Goetz, R. M., Thatte, H. S., Prabhakar, P., Cho, M. R., Michel, T., and Golan, D. E. 1999. Estradiol induces the calcium-dependent translocation of endothelial nitric oxide synthase. Proc. Natl. Acad. Sci. USA 96:2788–2793.PubMedCrossRefGoogle Scholar
  28. Greb, R. R., Heikinheimo, O., Williams, R. F., Hodgen, G. D., and Goodman, A. L. 1997. Vascular endothelial growth factor in primate endometrium is regualted by oestrogen-receptor and progesterone-receptor ligands in vivo. Hum. Reprod. 12:1280–1292.Google Scholar
  29. Green, S., Kumar, V., Krust, A., Walter, P., and Champon, P. 1986. Structural and functional domains of the estrogen receptor. Cold Spring Harb. Symp. Quant. Biol. 51:751–758.Google Scholar
  30. Greene, G. L., Gilna, P., Waterfield, M. A. B., Hort, Y., and Shine, J. 1986. Sequence and expression of human estrogen receptor complementary DNA. Science 231:1150–1154.PubMedCrossRefGoogle Scholar
  31. Grow, D. R., Reece, M. T., Hsiu, J. G., Adams, L., Newcomb, P., Williams, R. E, and Hodgen, G. D. 1998. Chronic antiprogestin therapy produces a stable atrophic endometrium with decreased fibroblast growth factor: a 1-year primate study on contraception and amenorrhea. Fertil. Steril. 69:936–943.CrossRefGoogle Scholar
  32. Halachmi, S., Marden, E., Martin, G., MacKay, H., Abbondanza, C., and Brown, M. 1994. Estrogen receptor-associated proteins: possible mediatros of hormone-induced transcription. Science 264:1455–1458.PubMedCrossRefGoogle Scholar
  33. Hashimoto, M., Akishita, M., Eto, M., Ishikawa, M., Kozaki, K., Toba, K., Sagara, Y., Taketani, Y., Orimo, H., and Ouchi, Y. 1995. Modulation of endothelium-dependent flow-mediated dilation of the brachial artery by sex and menstrual cycle. Circulation 92:3431–3435.PubMedCrossRefGoogle Scholar
  34. Hegele-Hartung, C., Fritzmeier, K.-H., and Diel, P. 1997. Effects of a pure antiestrogen on estrogen-mediated alterations of blood flow and progesterone receptor expression in the aorta of ovariectomized rabbits. J. Steroid Biochem. 63:237–249.CrossRefGoogle Scholar
  35. Hodges, Y. K., Richer, J. K., Horwitz, K. B., and Horwitz, L. D. 1999. Variant estrogen and progesterone receptor messages in human vascular smooth muscle. Circulation 99:2688–2693.PubMedCrossRefGoogle Scholar
  36. Hyder, S. M., Stancel, G. M., Chiapetta, C., Murthy, L., Boetter-Tong, H. L., and Makela, S. 1996. Uterine expression of vascular endothelial growth factor is increased by estradiol and tamoxifen. Cancer Res. 56:3954–3960.PubMedGoogle Scholar
  37. Iafrati, M. D., Karas, R. H., Aronovitz, M., King, M., Sullivan, T. R., Jr., Lubahn, D. B., O’Donnell, T. F., Korach, K. S., and Mendelsohn, M. E. 1997. Estrogen inhibits the vascular injury response in estrogen receptor a-deficient mice. Nat. Med. 3:545–548.PubMedCrossRefGoogle Scholar
  38. Iruela-Arispe, M., Porer, P., Bornstein, P., and Sage, E. H. 1996. Thrombospondin-1, an inhibitor of angiogenesis, is regulated by progesterone in the human endometrium. J. Clin. Invest. 97:403–412.PubMedCrossRefGoogle Scholar
  39. Jaggers, D. C., Collins, W. P., and Milligan, S. R. 1996. Potent inhibitory effects of steroids in an in vitro model of angiogenesis. J. Endocrinol. 150:457–464.PubMedCrossRefGoogle Scholar
  40. Joel, P. B., Traish, A. M., and Lannigan, D. A. 1998. Estradiol-induced phosphorylation of serine 118 in the estrogen receptor is independent of p42/p44 mitogen-activated protein kinase. J. Biol. Chem. 273:13317–13323.PubMedCrossRefGoogle Scholar
  41. Johns, A., Freay, A. D., Fraser, W., Korach, K. S., and Rubanyi, G. M. 1996. Disruption of estrogen receptor gene prevents 17 beta estradiol-induced angiogenesis in transgenic mice. Endocrinology 137:4511–4513.PubMedCrossRefGoogle Scholar
  42. Jones, G. S. 1991. Luteal phase defect. A review of pathophysiology. Curr. Opin. Obstet. Gynecol. 3:641–648.PubMedCrossRefGoogle Scholar
  43. Jun, S. S., Chen, Z., Pace, M. C., and Shaul, P. W. 1998. Estrogen upregulates cyclooxygenase1 gene expression in ovine fetal pulmonary artery endothelium. J. Clin. Invest. 102:176–183.Google Scholar
  44. Kaiserman-Abramof, I. R., and Padykula, H. A. 1989. Angiogenesis in the postovulatory primate endometrium: the coiled arteriolar system. Anat. Rec. 224:479–489.Google Scholar
  45. Kastner, P., Krust, A., Turcotte, B., Stropp, U., Tora, L., Gronemeyer, H., and Chambon, P. 1990. Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. EMBO J. 9:1603–1614.PubMedGoogle Scholar
  46. Kato, S., Endoh, H., Masuhiro, Y., Kitamoto, T., Uchiyama, S., Sasaki, H., Masushige, S., Gotoh, Y., Nishida, E., Kawashima, H., Metzger, D., and Chambon, P. 1995. Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science 270:1491–1494.PubMedCrossRefGoogle Scholar
  47. Keck, C., Herchenbach, D., Pfisterer, J., and Breckwoldt, M. 1998. Effects of 173-estradiol and progesterone on interleukin-6 production and proliferation of human umbilical vein endothelial cells. Exp. Clin. Endocrinol. Diabetes 106:334–339.PubMedCrossRefGoogle Scholar
  48. Kim-Schulze, S., Lowe Jr., W. L., and Schnaper, H. W. 1998. Estrogen induces mitogenactivated protein kinase (ERK 1/2) activity in endothelial cells via an autocrine loop involving basic fibroblast growth factor. Circulation 98:413–421.PubMedCrossRefGoogle Scholar
  49. Kim-Schulze, S., McGowan, K. A., Hubchak, S. C., Cid, M. C., Martin, M. B., Kleinman, H. K., Greene, G. L., and Schnaper, H. W. 1996. Expression of an estrogen receptor by human coronary artery and umbilical vein endothelial cells. Circulation 94:1402–1407.PubMedCrossRefGoogle Scholar
  50. Klauber, N., Parangi, S., Flynn, E., Hamel, E., and D’Amato, R. J. 1997. Inhibition of angiogenesis and breast cancer in mice by the microtubule inhibitors 2-methoxyestradiol and taxol. Cancer Res. 57:81–86.PubMedGoogle Scholar
  51. Kleinert, H., Wallerath, T., Euchenhofer, C., Ihrig-Biedert, I. Li H., and Förstermann, U. 1998. Estrogens incrase transcription of the human endothelial NO synthase gene. Analysis of the transcription factors involved. Hypertension 31:582–588.PubMedCrossRefGoogle Scholar
  52. Kraus, W. L., and Kadonaga, J. T. 1998. p300 and estrogen receptor cooperatively activate transcription via differential enhancement of initiation and reinitiation. Genes Dev. 12:331–342.PubMedCrossRefGoogle Scholar
  53. Kuiper, G. G., Carlsson, B., Grandien, K., Enmark, E., Haggblad, J., Nilsson, S., and Gustafsson, J. A. 1997. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 138:863–870.PubMedCrossRefGoogle Scholar
  54. Kumar, V., and Chambon, P. 1988. The estrogen receptor binds tightly to its responsive element as a ligand-induced homodimer. Cell 55:145–156.PubMedCrossRefGoogle Scholar
  55. Lansink, M., Koolwijk, P., van Hinsbergh, V., and Kooistra, T. 1998. Effect of steroid hormones and retinoids on the formation of capillary-like tubular structures of human microvascular endothelial cells in fibrin matrices is relatd to urokinse expression. Blood 92:927–938.PubMedGoogle Scholar
  56. Lee, H. S., Lee, I. S., Kang, T. C., Jeong, G. B., and Chang, S. I. 1999. Angiogenin is involved in morphological changes and angiogenesis in the ovary. Biochem. Biophys. Res. Commun. 257:182–186.Google Scholar
  57. Leung, B. S., and Potter, A. H. 1987. Mode of estrogen action on cell proliferation in CAMA-1 cells: II. Sensitivity of G1 phase population. J. Cell. Biochem. 34:213–225.PubMedCrossRefGoogle Scholar
  58. Loosfelt, H., Atger, M., Misrahi, M., Guichon-Mantel, A., Meriel, C. F. L., Logeat, F., Benarous, R., and Milgrom, E. 1986. Cloning and sequence analysis of rabbit progesterone-receptor complementary cDNA. Proc. Natl. Acad. Sci. USA 83:9045–9049.Google Scholar
  59. Losordo, D. W., Kearney, M., Kim, E. A., Jekanowski, J., and Isner, J. M. 1994. Variable expression of the estrogen receptor in normal and atherosclerotic coronary arteries of premenopausal women. Circulation 89:1501–1510.PubMedCrossRefGoogle Scholar
  60. Lowe, W. L., Pestell, R. G., Madison, L. D., and Jameson, J. L. 1998. Mechanisms of hormone action. In: Jameson, J. L., ed. Principles of Molecular Medicine. Humana Press, Totowa, NJ, pp. 419–431.Google Scholar
  61. Machiarelli, G., Nottola, S. A., Vizza, E., Kikuta, A., Murakami, T., and Motta, P. M. 1991. Ovarian microvasculature in normal and hCG stimulated rabbits. A study of vascular corrosion casts with particular regard to the interstitium. J. Submicrosc. Cytol. Pathol. 23:391–395.Google Scholar
  62. Mangelsdorf, D. J., Thummel, C., Beato, M., Herrlich, P., Schutz, G., Umesono, K., Blumberg, B., Kastner, P., Mark, M., Chambon, P., et al. 1995. The nuclear receptor superfamily: the second decade. Cell 83:835–839.PubMedCrossRefGoogle Scholar
  63. McDonnell, D. P., Clemm, D. L., Hermann, T., Goldman, M. E., and Pike, J. W. 1995. Analysis of estrogen receptor function in vitro reveals three distinct classes of antiestrogens. Mol. Endocrinol. 9:659–669.Google Scholar
  64. McGuire, J. K., and Schnaper, H. W. 1999. Estradiol induces cyclin-associated kinase activity in vascular endothelial cells. Pediatr. Res. 45:42A.Google Scholar
  65. Mendelsohn, M. E., and Karas, R. H. 1999. The protective effects of estrogen on the cardiovascular system. N. Engl. J. Med. 340:1801–1811.PubMedCrossRefGoogle Scholar
  66. Meyer, G. T., and McGeachie, J. K. 1988. Angiogenesis in the developing corpus luteum of pregnant rats: a stereologic and autoradiographic study. Anat. Rec. 222:18–25.Google Scholar
  67. Migliaccio, A., Di Domenico, M., Castoria, G., de Falco, A., Bontempo, P., Nola, E., and Auricchio, F. 1996. Tyrosine kinase/p21ras/MAP-kinase pathway activation by estradiolreceptor complex in MCF-7 cells. EMBO J. 15:1292–1300.PubMedGoogle Scholar
  68. Miller, V. M., and Vanhoutte, P. M. 1991. Progesterone and modulation of endothelium-dependent responses in canine coronary arteries. Am. J. Physiol. 261:R1022–R1027.PubMedGoogle Scholar
  69. Minshall, R. D., Stanczyk, F. Z., Miyagawa, K., Uchida, B., Axthelm, M., Novy, M., and Hermsmeyer, K. 1998. Ovarian steroid protection against coronary artery hyperreactivity in rhesus monkeys. J. Clin. Endocrinol. Metab. 83:649–659.PubMedCrossRefGoogle Scholar
  70. Morales, D. E., McGowan, K. A., Grant, D. S., Maheshwari, S., Bhartiya, D., Cid, M. C., Kleinman, H. K., and Schnaper, H. W. 1995. Estrogen promotes angiogenic activity in human umbilical vein endothelial cells in vitro and in a murine model. Circulation 91:755–763.PubMedCrossRefGoogle Scholar
  71. Musgrove, E. A., and Sutherland, R. L. 1994. Cell cycle control by steroid hormones. Semin. Cancer Biol. 5:381–389.Google Scholar
  72. Naftolin, F., and Tolis, G. 1978. Neuroendocrine regulation of the menstrual cycle. Clin. Obstet. Gynecol. 21:17–29.Google Scholar
  73. Nakamura, J., Lu, Q., Aberdeen, G., Albrecht, E., and Brodie, A. 1999. The effect of estrogen on aromatase and vascular endothjelial growth factor messenger ribonucleic acid in the normal nonhuman primate mammary gland. J. Clin. Endocrinol. Metab. 84:1432–1437.PubMedCrossRefGoogle Scholar
  74. Paech, K., Webb, P., Kuiper, G. G., Nilsson, S., Gustafsson, J., Kushner, P., and Scanlan, T. S. 1997. Differential ligand activation of estrogen receptors ERa and ER(3 at AP1 sites. Science 277:1508–1510.PubMedCrossRefGoogle Scholar
  75. Prendergast, P., Pan, Z., and Edwards, D. P. 1996. Progesterone receptor-induced bending of its target DNA: distinct effects of the A and B receptor forms. Mol. Endocrinol. 10:393–407.Google Scholar
  76. Raff, M. C., Barres, B. A., Burne, J. F., Coles, H., Ishizaki, Y., and Jacobson, M. D. 1993. Programmed cell death and the control of cell survival: lessons from the nervous system. Science 262:695–700.PubMedCrossRefGoogle Scholar
  77. Razandi, M., Pedram, A., Greene, G. L., and Levin, E. R. 1999. Cell membrane and nuclear estrogen receptors (ERs) originate from a single transcript: studies of ERa and ER(3 expressed in Chinese hamster ovary cells. Mol. Endocrinol. 13:307–319.Google Scholar
  78. Re, F., Zanetti, A., Sironi, M., Polentarutti, N., Lanfrancone, L., Dejana, E., and Colotta, A. 1994. Inhibition of anchorage-dependent cell spreading triggers apoptosis in cultured human endothelial cells. J. Cell Biol. 127:537–546.PubMedCrossRefGoogle Scholar
  79. Rodger, F. R., Young, F. M., Fraser, H. M., and Illingworth, P. J. 1997. Endothelial cell proliferation follows the mid-cycle luteinizing hormone surge, but not human chorionic gonadotropin rescue, in the human corpus luteum. Hum. Reprod. 12:1723–1729.Google Scholar
  80. Rogers, P. A. W., Lederman, F., and Taylor, N. 1998. Endometrial microvascular growth in normal and dysfunctional states. Hum. Reprod. Update 4:503–508.Google Scholar
  81. Rone, J. D., Halvorson, L. M., and Goodman, A. L. 1993. Ovarian angiogenesis in rabbits: endotheliotrophic chemoattractant activity from isolated follicles and dispersed granulosa cells. J. Reprod. Fertil. 97:359–365.PubMedCrossRefGoogle Scholar
  82. Russell, K. S., Haynes, M. P., Caulin-Glaser, T., et al. 2000. Estrogen stimulates heat shock protein 90 binding to endothelial nitric oxide synthase in human vascular endothelial cells. J. Biol. Chem. 275:5026–5030.PubMedCrossRefGoogle Scholar
  83. Rutqvist, L. E., and Mattson, A. 1993. Cardiac and thrombolic morbidity among postmenopausal women with early-stage breast cancer in a randomized trial of adjuvant tamoxifen. J. Natl. Cancer Inst. 85:1398–1406.PubMedCrossRefGoogle Scholar
  84. Saceda, M., Lippman, M. E., Chambon, P., and Lindsey, R. L., Ponglikitmongkol, M., Puente, M., and Martin, M. B. 1988. Regulation of the estrogen receptor in MCF-7 cells by estradiol. Mol. Endocrinol. 2:1157–1162.Google Scholar
  85. Savouret, J. F., Chauchereau, A., Misrahi, M., Lescop, P., Mantel, A., Bailly, A., and Milgrom, E. 1994. The progesterone receptor. Biological effects of progestins and antiprogestins. Hum. Reprod. 9(suppl):7–11.Google Scholar
  86. Schnaper, H. W. 1999. Estrogen: it’s not just for reproduction any more. Kidney Int. 55:1577–1579.PubMedCrossRefGoogle Scholar
  87. Schnaper, H. W, Albuquerque, M. L. C., McGuire, J., Kim-Schulze, S., Runyan, C., and Hubchak, S. C. 1999a. Modulation of endothelial cell function by estrogen. In: Rubanyi, G. M., ed. Angiogenesis in Health and Disease. Marcel Dekker, New York, pp. 175–190.Google Scholar
  88. Schnaper, H. W, McGuire, J., Runyan, C., and Hubchak, S. C. 1999b. Sex steroids and the endothelium. Curr. Med. Chem. 7:519–531.CrossRefGoogle Scholar
  89. Shiau, A. K., Barstad, D., Loria, P. M., Cheng, L., Kushner, P. J., Agard, D. A., and Greene, G. L. 1998. The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell 95:927–937.PubMedCrossRefGoogle Scholar
  90. Shifren, J. L., Tseng, J. F., Zaloudek, C. J., Ryan, I. P., Meng, Y. G., Ferrara, N., Jaffe, R. B., and Taylor, R. N. 1996. Ovarian steroid regulation of vascular endothelial growth factor in the human endometrium: implications for angiogenesis during the menstrual cycle and in the pathogenesis of endometriosis. J. Clin. Endocrinol. Metab. 81:3112–3118.Google Scholar
  91. Simoncini, T., Hafezi-Moghadam, A., Brazil, D. P., et al. 2000. Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature 407:538–541.PubMedCrossRefGoogle Scholar
  92. Spyridopoulos, I., Brogi, E., Kearney, M., Sullivan, A. B., Cetrulo, C., Isner, J. M., and Losorodo, D. W. 1997b. Vascular endothelial growth factor inhibits endothelial cell apoptosis induced by tumor necrosis factor-alpha: balance between growth and death signals. J. Mol. Cell. Cardiol. 29:1321–1330.CrossRefGoogle Scholar
  93. Spyridopoulos, I., Sullivan, A. B., Kearney, M., Isner, J. M., and Losordo, D. W. 1997a. Estrogen receptor-mediated inhibition of human endothelial cell apoptosis. Estradiol as a survival factor. Circulation 95:1505–1514.CrossRefGoogle Scholar
  94. Subakir, S. B., Hadisaputra, W., Handoyo, A. E., and Affandi, B. 1996. Endometrial angiogenic response in norplant users. Hum. Reprod. 11(suppl):51–55.Google Scholar
  95. Suzuki, T., Sasano, H., Takaya, R., Fukaya, T., Yajima, A., and Nagura, H. 1998. Cyclic changes of vasculature and vascular phenotypes in normal huan ovaries. Hum. Reprod. 13:953–959.Google Scholar
  96. Tempel, C., and Neeman, M. 1999. Perfusion of the rat ovary: application of pulsed arterial spin labeling MRI. Magn. Reson. Med. 41:113–123.Google Scholar
  97. Tsukamoto, A., Kaneko, Y., Yoshida, Y., Han, K., Ichinose, M., and Kimura, S. 1998. 2-Methoxyestradiol, an endogenous metabolite of estrogen, enhances apoptosis and ß-galactosidase expression in vascular endothelial cells. Biochem. Biophys. Res. Commun. 248:9–12.PubMedCrossRefGoogle Scholar
  98. Tsukuda, K., Matsushima, T., and Yamanaka, N. 1996. Neovascularization of the corpus luteum of rats during the estrus cycle. Pathol. Int. 46:408–416.Google Scholar
  99. Vazquez, F., Rodriguez-Manzaneque, J. C., Lydon, J. P., Edwards, D. P., O’Malley, B. W., and Iruela-Arispe, M. L. 1999. Progesterone regulates proliferation of endothelial cells. J. Biol. Chem. 274:2185–2192.PubMedCrossRefGoogle Scholar
  100. Venkov, C. D., Rankin, A. B., and Vaughan, D. E. 1996. Identification of authentic estrogen receptor in cultured endotehlial cells. A potential mechanism for steroid hormone regulation of endothelial function. Circulation 94:727–733.PubMedCrossRefGoogle Scholar
  101. White, R. E., Darkow, D. J., and Falvo Lang, J. L. 1995. Estrogen relaxes coronary arteries by opening BKCachannels through a cGMP-dependent mechanism. Circ. Res. 77:936–942.Google Scholar
  102. Williams, S., Leventhal, C., Lemmon, V., Nedergaard, M., and Goldman, S. A. 1999. Estrogen promotes the initial migration and inception of NgCAM-dependent calcium-signaling by new neurons of the adult songbird brain. Mol. Cell. Neurosci. 13:51–55.Google Scholar
  103. Xing, R. H., and Rabbani, S. A. 1999. Transcriptional regulation of urokinase (uPA) gene expression in breast cancer cells: role of DNA methylation. Int. J. Cancer 81:443–450.PubMedCrossRefGoogle Scholar
  104. Yamamoto, S., Konishi, I., Tsuruta, Y., Nanbu, K., Mandai, M., and Kuroda, H. 1997. Expression of vascular endothelual growth factor (VEGF) during follicular and corpus luteum formation in the human ovary. Gynecol. Endocrinol. 11:371–381.Google Scholar
  105. Yamamoto, T., Terada, N., Nishizawa, Y., and Petrow, V. 1994. Angiostatic activities of medroxyprogesterone acetate and its analogues. Int. J. Cancer 56:393–399.PubMedCrossRefGoogle Scholar
  106. Yasuda, Y., Masuda, S., Chikuma, M., Inoue, K., Nagao, M., and Sasaki, R. 1998. Estrogen-dependent production of erythropoietin in uterus and its implication in uterine angiogenesis. J. Biol. Chem. 273:25381–25387.PubMedCrossRefGoogle Scholar
  107. Yue, T.-L., Wang, X., Louden, C. S., Gupta, S., Pillarisetti, K., Gu, J.-L., Hart, T. K., Lysko, P. G., and Feuerstein, G. Z. 1997. 2-methoxyestradiol, an endogenous estrogen metabo-lite, induces apoptosis in endothelial cells and inhibits angiogenesis: possible role for stress-activated preotein kinase signaling pathway and Fas expression. Mol. Pharmacol. 51:951–962.PubMedGoogle Scholar
  108. Zhou, M., Sutliff, R. L., Paul, R. J., Lorenz, J. N., Hoying, J. B., Haudenschild, C. C., Yin, M., Coffin, J. D., Kong, L., Kranias, E. G., Luo, W., Boivin, G. P., Duffy, J. J., Pawlowski, S. A., and Doetschman, T. 1998. Fibroblast growth factor 2 control of vascular tone. Nat. Med. 4:201–207.Google Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • H. William Schnaper
  • Constance E. Runyan

There are no affiliations available

Personalised recommendations