Advertisement

Estradiol and Progesterone Receptors in Human Endometrium

  • Paul Robel
  • Rodrigue Mortel
  • Etienne Emile Baulieu

Abstract

In the last two decades, the development of saturation analysis methods has permitted specific and accurate measurement of circulating sex steroid hormones and documentation of their cyclic changes during the menstrual cycle. The large body of evidence accumulated over the past ten years indicates that hormones interact with a receptor system before triggering cellular responses. Hormone receptors were first identified and studied physiochemically for steroids, particularly estradiol, in the rat uterus. Once reliable measurements of hormone receptors became available in animal models, correlations between receptor concentrations and circulating levels of various hormones:were attempted. It was discovered that the concentration of receptor molecules is not fixed and varies with the physiological state of animals. Variations in the concentration and subcellular distribution of receptors were observed during the estrus cycle and could be mimicked in hormone-deprived animals by injecting estradiol and progesterone (Baulieu et al., 1975).

Keywords

Progesterone Receptor Menstrual Cycle Endometrial Carcinoma Receptor Site Human Endometrium 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Anderson, J., Clark, J.H., and Peck, E.J., 1972, Oestrogen and nuclear binding sites. Determination of specific sites by [3H]oestradiol exchange, Biochem. J., 126: 561.PubMedGoogle Scholar
  2. Batra, S., Grundsell, H., and Sjöberg, N.-O., 1977, Estradiol-173 and progesterone concentrations in human endometrium during the menstrual cycle, Contraception, 16:217.CrossRefGoogle Scholar
  3. Baulieu, E.E., Atger, M., Best-Belpomme, M., Corvol, P., Courvalin, J.C., Mester, J., Milgrom, E., Robel, P., Rochefort, H., and De Catalogne, D., 1975, Steroid hormone receptors, Vitam. Horm., 33:649.PubMedCrossRefGoogle Scholar
  4. Bayard, F., Louvet, J.P., Monrozies, M., Boulard, A., and Pontonnier, G., 1975, Endometrial progesterone concentrations during the menstrual cycle, J. Endocrinol. Metab., 41:412.CrossRefGoogle Scholar
  5. Bayard, F., Damilano, S., Robel, P., and Baulieu, E.E., 1978, Cytoplasmic and nuclear estradiol and progesterone receptors in human endometrium, J. Clin. Endocrinol. Metab., 46:635.PubMedCrossRefGoogle Scholar
  6. Brenner, R.M., Resko, J.A., and West, N.B., 1974, Cyclic changes in ovaductal morphology and residual cytoplasmic estradiol binding capacity induced by sequential estradiol-progesterone treatment of spayed rhesus monkeys, Endocrinology, 95:1094.PubMedCrossRefGoogle Scholar
  7. Brush, M.G., Taylor, R.W., and King, R.J.B., 1967, The uptake of [6,7- H]oestradiol by the normal human female reproductive tract, J. Endocrinol., 39:599.PubMedCrossRefGoogle Scholar
  8. Brush, M.G., King, R.J.B., and Taylor, R.W., 1978, “Endometrial Cancer,” Baillière Tindall, London.Google Scholar
  9. Collins, J.A., and Jewkes, D.M., 1974, Progesterone metabolism by proliferative and secretory human endometrium, Am. J. Obstet. Gynecol., 118:179.PubMedGoogle Scholar
  10. Crocker, S.G., Milton, P.J.D., and King, R.J.B., 1974, Uptake of [6,73-H]oestradiol-173 by normal and abnormal human endometrium, J. Endocrinol., 62:145.PubMedCrossRefGoogle Scholar
  11. Davis, M.E., Wiener, M., Jacobson, H.I., and Jensen, E.V., 1963, Estradiol metabolism in pregnant and nonpregnant women, Am. J. Obstet. Gynecol., 87:979.Google Scholar
  12. Evans, L.H., and Hähnel, R., 1971, Oestrogen receptors in human uterine tissue, J . Endocrinol., 50:209.PubMedCrossRefGoogle Scholar
  13. Evans, L.H., Martin, J.D., and Hahnel, R., 1974, Estrogen receptor concentration in normal and pathological human uterine tissues, J. Clin. Endocrinol. Metab., 38:23.PubMedCrossRefGoogle Scholar
  14. Feil, P.D., Glasser, S.R., Toft, D.O., and O’Malley, B.W., 1972, Progesterone binding in the mouse and rat uterus, Endocrinology, 91:738.PubMedCrossRefGoogle Scholar
  15. Guerrero, R., Landgren, B.-M., Monteil, R., Cekan, Z., and Diczfalusy, E., 1975, Unconjugated steroids in the human endometrium, Contraception, 11:169.PubMedCrossRefGoogle Scholar
  16. Gurpide, E., Gusberg, S., and Tseng, L., 1976, Estradiol binding and metabolism in human endometrial hyperplasia and adenocarcinoma, J. Steroid Biochem., 7:891.PubMedCrossRefGoogle Scholar
  17. Gurpide, E., Tseng, L., and Gusberg, S.B., 1977, Estrogen metabolism in normal and neoplastic endometrium, Am. J. Obstest. Gynecol., 129:809.Google Scholar
  18. Gusberg, S., 1976, The individual at high risk for endometrial carcinoma, Am. J. Obstet. Gynecol., 126:535.PubMedGoogle Scholar
  19. Hahnel, R., 1971, Properties of the estrogen receptor in the soluble fraction of human uterus, Steroids, 17:105.PubMedCrossRefGoogle Scholar
  20. Haukkamaa, M., 1974, Binding of progesterone by rat myometrium during pregnancy and by human myometrium in late pregnancy, J. Steroid Biochem., 5:73.PubMedCrossRefGoogle Scholar
  21. Haukkamaa, M., and Luukkainen, T., 1974, The cytoplasmic progesterone receptor of human endometrium during the menstrual cycle, J. Steroid Biochem, 5:447.PubMedCrossRefGoogle Scholar
  22. Heyns, W., and De Moor, P., 1971, The binding of 17β-hydroxy-5α-androstan-3-one to the steroid-binding β-globulin in human plasma, as studied by means of ammonium sulfate precipitation, Steroids, 18:709.PubMedCrossRefGoogle Scholar
  23. Hsueh, A.J., Peck, E.J., and Clark, J.H., 1975, Progesterone antagonism of the oestrogen receptor and oestrogen-induced uterine growth, Nature, 254:337.PubMedCrossRefGoogle Scholar
  24. Illingworth, D.V., Wood, G.P., Flickinger, G.L., and Mikhail, G., 1975, Progesterone receptor of the human myometrium, J. Clin. Endocrinol. Metab., 40:1001.PubMedCrossRefGoogle Scholar
  25. Jänne, O., Kontula, K., Luukkainen, T., and Vihko, R., 1975, Oestrogen-induced progesterone receptor in human uterus, J. Steroid Biochem., 6:501.PubMedCrossRefGoogle Scholar
  26. Janne, O., Kontula, K., and Vihko, R., 1976, Progestin receptors in human tissues: concentrations and binding kinetics, J. Steroid Biochem., 7:1061.PubMedCrossRefGoogle Scholar
  27. Koenders, A.J., Geurts-Moespot, J., Kho, K.H., and Benraad, Th.J., 1978, Estradiol and progesterone receptor activities in stored lyophilised target tissue, J. Steroid Biochem., 9:947.PubMedCrossRefGoogle Scholar
  28. Kontula, K., 1975, Progesterone-binding protein in human myometrium. Binding site concentration in relation to endogenous proges-terine and estradiol-17β levels, J. Steroid Biochem., 7:1555.CrossRefGoogle Scholar
  29. Kreitmann, B., Derache, B., and Bayard, F., 1978, Measurement of the corticosteroid-binding globulin, progesterone, and progesterone “receptor” content in the human endometrium, J. Clin. Endocrinol. Metab., 47:350.PubMedCrossRefGoogle Scholar
  30. Krishnan, A.R., Hingorani, V., and Laumas, K.R., 1973, Binding of 3H-oestradiol with receptors in the human endometrium and myometrium, Acta Endocrinol., 74:756.PubMedGoogle Scholar
  31. Levy, C., Robel, P., Gautray, J.P., de Brux, J., Verma, U., 1980a, Estradiol and progesterone receptors in human endometrium, normal and abnormal menstrual cycles and early pregnancy, Am. J. Obstet. Gynecol., 136:646.Google Scholar
  32. Levy, C., Mortel, R., Eychenne, B., Robel, P., and Baulieu, E.E., 1980, Unoccupied nuclear oestradiol-receptor sites in normal human endometrium, Biochem. J., 185:733.PubMedGoogle Scholar
  33. Lippman, M., Huff, K., Bolan, G., and Neifeld, J.P., 1977, Interactions of R5020 with progesterone and glucorticoid receptors in breast cancer and peripheral blood lymphocytes in vitro, in; “Progesterone Receptors in Normal and Neoplastic Tissues,” W.L. McGuire, J.P. Raynaud, and E.E. Baulieu, ed., Raven Press, New York, p. 193.Google Scholar
  34. Lunan, C.B., and Green, B., 1975, Oestradiol-17β uptake in vitro into the nuclei of endometrium from different regions of the human uterus, Acta Endocrinol., 78:353.PubMedGoogle Scholar
  35. McGuire, W.L., Raynaud, J.P., and Baulieu, E.E., 1977, Progesterone receptors: introduction and overview, in: “Progesterone Receptors in Normal and Neoplastic Tissues,” W.L. McGuire, J.P. Raynaud, and E.E. Baulieu, ed., Raven Press, New York, p. 1.Google Scholar
  36. MacLaughlin, D.T., and Richardson, G.S., 1976, Progesterone binding by normal and abnormal human endometrium, J. Clin. Endocrinol. Metab., 42:667.CrossRefGoogle Scholar
  37. Makler, A., and Eisenfeld, A.J., 1974, In vitro binding of 3H-estradiol to macromolecules from the human endometrium, J. Clin. Endocrinol. Metab., 38:628.CrossRefGoogle Scholar
  38. Mercier-Bodard, C., Alfsen, A., and Baulieu, E.E., 1970, Sex steroid binding plasma protein (SBP), Acta Endocrinol., 147:204.Google Scholar
  39. Mester, I., Martel, D., Psychoyos, A., and Baulieu, E.E., Hormonal control of oestrogen receptor in uterus and receptivity for ovoimplantation in the rat, Nature, 250:776.Google Scholar
  40. Milgrom, E., and Baulieu, E.E., 1970, Progesterone in uterus and plasma. I. Binding in rat uterus 105,000g supernatant, Endocrinology, 87:276.PubMedCrossRefGoogle Scholar
  41. Milgrom, E., Atger, M., Perrot, M., and Baulieu, E.E., 1972, Progesterone in uterus plasma. VI. Uterine progesterone receptors during the estrus cycle and implantation in the guinea pig, Endocrinology, 90:1071.PubMedCrossRefGoogle Scholar
  42. Milgrom, E., Thi, M.L., Atger, M., and Baulieu, E.E., 1973, Mechanisms regulating the concentration and the conformation of progesterone receptor(s) in the uterus, J. Biol. Chem., 248:6366.PubMedGoogle Scholar
  43. Philibert, D., and Raynaud, J.P., 1974, Binding of progesterone and R 5020, a highly potent progestin, to human endometrium and myometrium, Contraception, 10:457.PubMedCrossRefGoogle Scholar
  44. Pollow, K., Lübbert, H., Boquoi, E., Kreutzer, G., and Pollow, B., 1975a, Characterization and comparison of receptors of 17ß-estradiol and progesterone in human proliferative and endometrial carcinoma, Endocrinology, 96:319.CrossRefGoogle Scholar
  45. Pollow, K., Lübbert, H., Boquoi, E., Kreutzer, G., Jeske, R., and Pollow, B., 1975b, Studies on 17β-hydroxysteroid dehydrogenase in human endometrium and endometrial carcinoma. I. Subcellular distribution and variations of specific enzyme activity, Acta Endocrinol., 79:134.Google Scholar
  46. Pollow, K., Lübbert, H., Boquoi, E., and Pollow, B., 1975c, Progesterone metabolism in normal endometrium during the menstrual cycle in endometrial carcinoma, J. Clin. Endocrinol. Metab., 41:729.CrossRefGoogle Scholar
  47. Pollow, K., Boquoi, E., Schmidt-Gollwitzer, M., and Pollow, B., 1976, The nuclear estradiol and progesterone receptors of human endometrium and endometrial carcinoma, J. Mol. Med., 1:325.Google Scholar
  48. Pollow, K., Schmidt-Gollwitzer, M., Boquoi, E., and Pollow, B., 1978, Influence of estrogens and gestagens on 17β-hydroxy-steroid dehydrogenase in human endometrium and endometrial carcinoma, J. Mol. Med., 3:81.Google Scholar
  49. Powell, B., Garola, R.E., Chamness, G.C., and McGuire, W.L., 1979, Measurement of progesterone receptor in human breast cancer biopsies, Cancer Res., 39:1678.PubMedGoogle Scholar
  50. Rao, B.R., Wiest, W.G., and Allen, W.M., 1974, Progesterone “receptor” in human endometrium, Endocrinology, 95:1275.Google Scholar
  51. Raynaud, J.P., 1977, R 5020, a tag for the progestin receptor, in: “Progesterone Receptors in Normal and Neoplastic Tissues,” W.L. McGuire, J.P. Raynaud, and E.E. Baulieu, ed., Raven Press, New York, p. 9.Google Scholar
  52. Raynaud, J.P., Martin, P.M., Bouton, M.M., and Ojasoo, T., 1978, llβ-methoxy-17-ethynyl-l,3,5(10)-estratriene-3,17ß-diol (Moxestrol), a tag for estrogen receptor binding sites in human tissues, Cancer Res., 38:3044.PubMedGoogle Scholar
  53. Richardson, G.S., and MacLaughlin, E.T., 1978, “Hormonal Biology of Endometrial Cancer,” Vol. 42, UICC Technical Reports Series, Geneva.Google Scholar
  54. Robel, P., Levy, C., Wolff, J.P., Nicolas, J.C., and Baulieu, E.E., 1978, Réponse à un anti-oestrogène comme critère d’hormono-sensibilité du cancer de l’endomètre, C.R. Acad. Sci. Paris, 287:1353.Google Scholar
  55. Robertson, D.M., Mester, J., Beilby, J., Steele, S.J., and Kellie, A.E., 1971, The measurement of high-affinity oestradiol receptors in human uterine endometrium and myometrium, Acta Endocrinol., 68:534.PubMedGoogle Scholar
  56. Sanborn, B.M., Kuo, H.S., and Held, B., 1978, Estrogen and progestogen binding site concentrations in human endometrium and cervix throughout the menstrual cycle and in tissue from women taking oral contraceptives, J. Steroid Biochem., 9:951.PubMedCrossRefGoogle Scholar
  57. Schmidt-Gollwitzer, M., Genz, T., Schmidt-Gollwitzer, K., Pollow, B., and Pollow, K., 1978, Correlation between oestradiol and progesterone receptor levels, 17β-hydroxysteroid dehydrogenase activity and endometrial tissue levels of oestradiol, pestrone and progesterone in women, in: “Endometrial Cancer,” M.G. Brush, R.J.B. King, and R.W. Taylor, ed., Baillière-Tindall, London, p. 227.Google Scholar
  58. Scublinski, A., Marin, C., and Gurpide, E., 1976, Localization of estradiol 173 dehydrogenase in human endometrium, J. Steroid Biochem., 7:745.CrossRefGoogle Scholar
  59. Seematter, R.J., Hoffman, P.G., Kuhn, R.W., Lockwood, L.C., and Siiteri, P.K., 1978, Comparison of [3H] progesterone and [6,7–3H]-17, 21-dimethyl-19-norpregna-4,9-diene-3,20-dione for the measurement of progesterone receptors in human malignant tissue, Cancer Res., 38:2800.PubMedGoogle Scholar
  60. Sutherland, R., Mester, J., and Baulieu, E.E., 1977, Tamoxifen is a potent ‘pure’ anti-oestrogen in the chick oviduct, Nature, 267:434.PubMedCrossRefGoogle Scholar
  61. Sweat, M.L., and Bryson, M.J., 1970, Comparative metabolism of progesterone in proliferative human endometrium and myometrium, Am. J. Obstet. Gynecol., 106:193.PubMedGoogle Scholar
  62. Syrjälä, P., Kontula, K., Jämie, O., Kauppila, A., and Vihko, R., 1978, Steroid receptors in normal and neoplastic human uterine tissue, in: “Endometrial Cancer,” M.G. Brush, R.J.B. King, and R.W. Taylor, ed., Baillière-Tindall, London, p. 242.Google Scholar
  63. Trams, G., Engel, B., Lehmann, F., and Maass, H., 1973, Specific binding of oestradiol in human uterine tissue, Acta Endocrinol., 72:351.PubMedGoogle Scholar
  64. Tseng, L., and Gurpide, E., 1972a, Nuclear concentration of estradiol in superfused slices of human endometrium, Am. J. Obstet. Gynecol., 114:995.Google Scholar
  65. Tseng, L., and Gurpide, E., 1972b, Changes in the in vitro metabolism of estradiol by human endometrium during the menstrual cycle, Am. J. Qbstet. Gynecol., 114:1002.Google Scholar
  66. Tseng, L., and Gurpide, E., 1974, Estradiol and 20a-dihydroproges-terone dehydrogenase activities in human endometrium during the menstrual cycle, Endocrinology, 94:419.PubMedCrossRefGoogle Scholar
  67. Tseng, L., and Gurpide, E., 1975a, Induction of human endometrial estradiol dehydrogenase by progestins, Endocrinology, 97:825.CrossRefGoogle Scholar
  68. Tseng, L., and Gurpide, E., 1975b, Effects of progestins on estradiol receptor levels in human endometrium, J. Clin. Endocrinol. Metab., 41:402.CrossRefGoogle Scholar
  69. Tseng, L., Gusberg, S.B., and Gurpide, E., 1977, Estradiol receptor and 17β-dehydrogenase in normal and abnormal human endometrium, Ann. N.Y. Acad. Sci., 286:190.PubMedCrossRefGoogle Scholar
  70. Tsibris, J.C.M., Cazenave, C.R., Cantor, B., Notelovitz, M., Kalra, P.S., and Spellacy, W.N., 1978, Distribution of cytoplasmic estrogen and progesterone receptors in human endometrium, Am. J. Qbstet. Gynecol., 132:449.Google Scholar
  71. Verma, U., and Laumas, K.R., 1973, In vitro binding of progesterone to receptors in the human endometrium and the myometrium, Biochem. Biophys. Acta, 317:403.PubMedGoogle Scholar
  72. Wiest, W.G., and Rao, B.R., 1971, in: “Advances in the Biosciences,” G. Raspe, ed., Vol. VII, p. 251.Google Scholar
  73. Young, P.C.M., and Cleary, R.E., 1974, Characterization and properties of progesterone-binding components in human endometrium, J. Clin. Endocrinol. Metab., 39:425.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • Paul Robel
    • 1
  • Rodrigue Mortel
    • 1
  • Etienne Emile Baulieu
    • 1
  1. 1.Unité de Recherches sur le Métabolisme Moléculaire et la Physio-pathologie des StéroidesL’institut National de la Sante et de la Recherche, Médicale, (U 33 INSERM) and ER 125 CNRSBicetreFrance

Personalised recommendations