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Endocrine

, Volume 6, Issue 3, pp 301–307 | Cite as

Progesterone-dependent decidualization of the human endometrium is mediated by cAMP

  • Anoop K. Brar
  • Graeme R. Frank
  • Cherie A. Kessler
  • Marcelle I. Cedars
  • S. Handwerger
Original Articles

Abstract

Progesterone is a key factor in regulating endometrial cell decidualization, but the signal transduction pathways involved in mediating the effects of progesterone are not known. A role of the cAMP pathway in decidualization has been suggested by in vitro studies demonstrating that cAMP agonists can stimulate decidualization, in the absence of sex steroids. In this article, we have used an in vitro culture model of progesterone-dependent decidualization of human endometrial stromal cells to examine whether progesterone-induced decidualization is associated with activation of the cAMP signal transduction pathway in which the prolactin gene expression is a marker of decidualization. Following a lag period of approx 3 d, progesterone induced prolactin secretion and elevated intracellular cAMP levels. By d 15, cAMP and prolactin levels were approx 10- and 60-fold greater, respectively, than those on d 3. Changes in cAMP levels showed a positive correlation with prolactin secretion. Prostaglandin E2 (PGE2), which enhances progesterone-dependent decidualization, also increased both prolactin secretion and cAMP levels approx two- to fourfold on d 15 compared with d 3, whereas PGE2 alone, which does not induce decidualization, did not stimulate prolactin secretion or intracellular cAMP accumulation. Conversely, all-trans retinoic acid, which attenuates progesterone-dependent decidualization, significantly (p<0.05) decreased both prolactin secretion and cAMP levels. Furthermore, the protein kinase A (PKA) inhibitor, 8-bromoadenosine-3′,5′-cyclic monophosphorothioate, significantly (p<0.05) suppressed progesterone-dependent prolactin expression. Since activation of the PGE2 receptor subtype EP2 stimulates adenylate cyclase, reverse transcription-polymerase chain reaction (RT-PCR) analysis of endometrial cells was undertaken. Expression of EP2 mRNA was induced in cells treated with progesterone and estradiol alone or with PGE2, compared with untreated controls. The data suggest that the cAMP signal transduction cascade is activated during progesterone-dependent decidualization.

Key Words

Decidualization endometrium cAMP human progesterone 

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References

  1. 1.
    Tang, B., Guller, S., and Gurpide, E. (1993).Endocrinology 133, 2197–2203.PubMedCrossRefGoogle Scholar
  2. 2.
    Gellersen, B., Kempf, R., Telgmann, R., and DiMattia, G. E. (1994).Mol. Endocrinol. 8, 356–373.PubMedCrossRefGoogle Scholar
  3. 3.
    Tanaka, N., Miyazaki, K., Tashiro, H., Mizutani, H., and Okamura, H. (1993).J. Reprod. Fertil. 97, 33–39.Google Scholar
  4. 4.
    Bergamini, C. M., Pansini, F., Bettocchi, S., Jr., Segala, V., Dallocchio, F., Bagni, B., and Mollica, G. (1985).J. Steroid Biochem. 22, 299–303.PubMedCrossRefGoogle Scholar
  5. 5.
    Houserman, V. L., Todd, H. and Hertelendy, F. (1989).J. Reprod. Fert. 85, 195–202.CrossRefGoogle Scholar
  6. 6.
    Coleman, R. A., Smith, W. L., and Narumiya, S. (1994).Pharmacol. Rev. 46, 205–229.PubMedGoogle Scholar
  7. 7.
    Irwin, J. C., Utian, W. H., and Eckert, R. L. (1991).Endocrinology 129, 2385–2392.PubMedCrossRefGoogle Scholar
  8. 8.
    Brar, A. K., Frank, G. R., Richards, R. R., Meyer, A. J., Kessler, C. A., Cedars, M. I., Klein, D. J., and Handwerger, S. (1995).J. Cell. Physiol. 163, 30–37.PubMedCrossRefGoogle Scholar
  9. 9.
    Frank, G. R., Brar, A. K., Cedars, M. I., and Handwerger, S. (1993).Endocrinology 134, 258–263.CrossRefGoogle Scholar
  10. 10.
    Brar, A. K., Kessler, C. A., Meyer, A. J., Cedars, M. I., and Jikihara, H. (1996).Mol. Human Reproduction 2, 185–193.CrossRefGoogle Scholar
  11. 11.
    Frank, G. R., Brar, A. K., Jikihara, H., Cedars, M. I., and Handwerger, S. (1995).Biol. Reprod. 52, 184–191.PubMedCrossRefGoogle Scholar
  12. 12.
    Zhou, J., Dsupin, B. A., Giudice, L. A., and Bondy, C. A. (1994).J. Clin. Endocrinol. Metab. 79, 1723–1734.PubMedCrossRefGoogle Scholar
  13. 13.
    Telgmann, R., Maronde, E., Tasken, K., and Gellersen, B. (1997).Endocrinology 138, 929–937.PubMedCrossRefGoogle Scholar
  14. 14.
    Cho, H., Aronica, S. M., and Katzenellenbogen, B. S. (1994).Endocrinology 134, 658–664.PubMedCrossRefGoogle Scholar
  15. 15.
    Park-Sarge, O.-K. and Sarge, K. D. (1995).Endocrinology 136, 5430–5437.PubMedCrossRefGoogle Scholar
  16. 16.
    Sirotkin, A. V. and Nitray, J. (1993).J. Steroid Biochem. Mol. Biol. 46, 573–577.PubMedCrossRefGoogle Scholar
  17. 17.
    Beck, L., Mularoni, A., Cardis, P., Adessi, G. L., and Nicollier, M. (1995).Endocrinology 136, 1737–1743.PubMedCrossRefGoogle Scholar
  18. 18.
    Yee, G. M. and Kennedy, T. G. (1991).Biol. Reprod. 45, 163–171.PubMedCrossRefGoogle Scholar
  19. 19.
    Fortier, M. A., Boulanger, M., Boulet, A. P., and Lambert, R. D. (1987).Biol. Reprod. 36, 1025–1033.PubMedCrossRefGoogle Scholar
  20. 20.
    Regan, J. W., Bailey, T. J., Pepperl, D. J., Pierce, K. L., Bogardus, A. M., Donello, J. E., Fairbairn, C. E., Kedzie, K. M., Woodward, D. F., and Gil, D. W. (1994).Prostaglandins 47, 151–168.CrossRefGoogle Scholar
  21. 21.
    Negishi, M., Sugimoto, Y., and Ichikawa, A. (1995).J. Lipid Mediators Cell Signalling 12, 379–391.CrossRefGoogle Scholar
  22. 22.
    Kennedy, T. G., Martel, D., and Psychoyos, A. (1983).Biol. Reprod. 29, 556–564.PubMedCrossRefGoogle Scholar
  23. 23.
    de Bustros, A., Ball, D. W., Peters, R., Compton, D., and Nelkin, B. D. (1992).Biochem. Biophys. Res. Commun. 189, 1157–1164.PubMedCrossRefGoogle Scholar
  24. 24.
    Vallejo, M. (1994).J. Neuroendocrinol. 6, 587–596.PubMedCrossRefGoogle Scholar
  25. 25.
    Muro, A. F., Bernath, V. A., and Kornblihtt, A. R. (1992).J. Biol. Chem. 267, 12,767–12,774.Google Scholar
  26. 26.
    Kinane, T. B., Shang, C., Finder, J. D., and Ercolani, L. (1993).J. Biol. Chem. 268, 24,669–24,676.Google Scholar
  27. 27.
    Andersen, B., Kennedy, G. C., Hamernik, D. L., Bokar, J. A., Bohinski, R., and Nilson, J. H. (1990).Mol. Endocrinol. 4, 573–582.PubMedCrossRefGoogle Scholar
  28. 28.
    Boularand, S., Darmon, M. C., Ravassard, P., and Mallet, J. (1995).J. Biol. Chem. 270, 3757–3764.PubMedCrossRefGoogle Scholar
  29. 29.
    Markoff, E., Zeitler, P., Peleg, S., and Handwerger S. (1983).J. Clin. Endocrinol. Metab. 56, 962–968.PubMedCrossRefGoogle Scholar
  30. 30.
    Irwin, J. C., Kirk, D., King, R. J., Quigley, M. M. and Gwatkin, R. B. (1989).Fertil. Steril. 52, 761–768.PubMedGoogle Scholar
  31. 31.
    Golander, A., Hurley, T., and Handwerger, S. (1979).J. Endocrinol. 82, 263–267.PubMedCrossRefGoogle Scholar
  32. 32.
    Chomczynski, P. and Sacchi, N. (1987).Anal. Biochem. 162, 156–159.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 1997

Authors and Affiliations

  • Anoop K. Brar
    • 1
  • Graeme R. Frank
    • 1
  • Cherie A. Kessler
    • 1
  • Marcelle I. Cedars
    • 2
  • S. Handwerger
    • 1
  1. 1.Department of Pediatric EndocrinologyChildren's Hospital Medical CenterCincinnati
  2. 2.Department of Obstetrics and GynecologyUniversity of Cincinnati Medical CenterCincinnati

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