A proposed mechanism for progesterone regulation of trophoblast MMP2 transcription independent of classical progesterone response elements on its promoter

Open Access
Hypothesis

Abstract

Background

Progesterone receptor act as ligand-inducible transcription factor in the respective target cells by binding to specific progesterone response elements in the promoter of the target genes. However, despite the lack of the classical progesterone response elements on matrix-metalloproteinase-2 promoter, progesterone has been shown to decrease the activity of this promoter

Presentation of the hypothesis

It has recently been suggested that in addition to interacting with their classical co-activators and co-repressors, progesterone receptor are capable of binding to several transcription factors. By interacting with other classes of transcription factors, progesterone receptor is capable of transcriptional activation through the transcription factors cognate DNA binding site.

Testing the hypothesis

Exploring transcription factors and transcription binding sites, interacting with the progesterone receptor in modulation of the matrix-metalloproteinase promoter.

Implications of the hypothesis

Identification of additional endogenous progesterone target genes makes it possible to further explore the signaling mechanisms by which the hormone regulates biological actions. Furthermore, the concepts of ligand-driven conformational diversity and selective tissue actions can be exploited in the future for drug development which selectively regulate orphan receptors from the nuclear receptor family.

Notes

References

  1. 1.
    Gronemeyer H: Control of transcription activation by steroid hormone receptors. FASEB J. 1992, 6: 2524-2529. ReviewCrossRefGoogle Scholar
  2. 2.
    Leonhardt SA, Boonyaratanakornkit V, Edwards DP: Progesterone receptor transcription and non-transcription signaling mechanisms. Steroids. 2003, 68: 761-770. 10.1016/S0039-128X(03)00129-6. ReviewCrossRefPubMedGoogle Scholar
  3. 3.
    Conneely OM, Mulac-Jericevic B, Lydon JP: Progesterone-dependent regulation of female reproductive activity by two distinct progesterone receptor isoforms. Steroids. 68: 771-778. 10.1016/S0039-128X(03)00126-0. ReviewCrossRefGoogle Scholar
  4. 4.
    Wardell SE, Edwards DP: Mechanisms controlling agonist and antagonist potential of selective progesterone receptor modulators (SPRMs). Semin Reprod Med. 2005, 23: 9-21. 10.1055/s-2005-864030. ReviewCrossRefPubMedGoogle Scholar
  5. 5.
    Rayasam GV, Elbi C, Walker DA, Wolford R, Fletcher TM, Edwards DP, Hager GL: Ligand-specific dynamics of the progesterone receptor in living cells and during chromatin remodeling in vitro. Mol Cell Biol. 2005, 25: 2406-2418. 10.1128/MCB.25.6.2406-2418.2005.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Conneely OM, Lydon JP: Progesterone receptors in reproduction: functional impact of the A and B isoforms. Steroids. 2000, 65: 571-577. 10.1016/S0039-128X(00)00115-X. ReviewCrossRefPubMedGoogle Scholar
  7. 7.
    Li X, O'Malley BW: Unfolding the action of progesterone receptors. J Biol Chem. 2003, 278: 39261-39264. 10.1074/jbc.R300024200. ReviewCrossRefPubMedGoogle Scholar
  8. 8.
    Leonhardt SA, Boonyaratanakornkit V, Edwards DP: Progesterone receptor transcription and non-transcription signaling mechanisms. Steroids. 2003, 68: 761-770. 10.1016/S0039-128X(03)00129-6. ReviewCrossRefPubMedGoogle Scholar
  9. 9.
    Shibata H, Spencer TE, Onate SA, Jenster G, Tsai SY, Tsai MJ, O'Malley BW: Role of co-activators and co-repressors in the mechanism of steroid/thyroid receptor action. Recent Prog Horm Res. 1997, 52: 141-164. ReviewPubMedGoogle Scholar
  10. 10.
    Chua SS, Ma Z, Ngan E, Tsai SY: Cdc25B as a steroid receptor coactivator. Vitam Horm. 2004, 68: 231-256. ReviewCrossRefGoogle Scholar
  11. 11.
    Shupnik MA: Crosstalk between steroid receptors and the c-Src-receptor tyrosine kinase pathways: implications for cell proliferation. Oncogene. 2004, 23: 7979-7989. 10.1038/sj.onc.1208076. ReviewCrossRefPubMedGoogle Scholar
  12. 12.
    Agoulnik IU, Krause WC, Bingman WE, Rahman HT, Amrikachi M, Ayala GE, Weigel NL: Repressors of androgen and progesterone receptor action. J Biol Chem. 2003, 278: 31136-31148. 10.1074/jbc.M305153200.CrossRefPubMedGoogle Scholar
  13. 13.
    Wang D, Simons SS: Corepressor binding to progesterone and glucocorticoid receptors involves the activation function-1 domain and is inhibited by molybdate. Mol Endocrinol. 2005, 19: 1483-1500. 10.1210/me.2005-0012.CrossRefPubMedGoogle Scholar
  14. 14.
    Christian M, Pohnke Y, Kempf R, Gellersen B, Brosens JJ: Functional association of PR and CCAAT/enhancer-binding protein beta isoforms: promoter-dependent cooperation between PR-B and liver-enriched inhibitory protein, or liver-enriched activatory protein and PR-A in human endometrial stromal cells. Mol Endocrinol. 2002, 16: 141-154. 10.1210/me.16.1.141.CrossRefPubMedGoogle Scholar
  15. 15.
    Zhang XL, Zhang D, Michel FJ, Blum JL, Simmen FA, Simmen RC: Selective interactions of Kruppel-like factor 9/basic transcription element-binding protein with progesterone receptor isoforms A and B determine transcriptional activity of progesterone-responsive genes in endometrial epithelial cells. J Biol Chem. 2003, 278: 21474-21482. 10.1074/jbc.M212098200.CrossRefPubMedGoogle Scholar
  16. 16.
    Hewetson A, Chilton BS: An Sp1-NF-Y/progesterone receptor DNA binding-dependent mechanism regulates progesterone-induced transcriptional activation of the rabbit RUSH/SMARCA3 gene. J Biol Chem. 2003, 278: 40177-40185. 10.1074/jbc.M303921200.CrossRefPubMedGoogle Scholar
  17. 17.
    Young KA, Stouffer RL: Gonadotropin and steroid regulation of matrix metalloproteinases and their endogenous tissue inhibitors in the developed corpus luteum of the rhesus monkey during the menstrual cycle. Biol Reprod. 2004, 70: 244-252. 10.1095/biolreprod.103.022053.CrossRefPubMedGoogle Scholar
  18. 18.
    Di Nezza LA, Jobling T, Salamonsen LA: Progestin suppresses matrix metalloproteinase production in endometrial cancer. Gynecol Oncol. 2003, 89: 325-333. 10.1016/S0090-8258(03)00089-1.CrossRefPubMedGoogle Scholar
  19. 19.
    Huang HF, Hong LH, Tan Y, Sheng JZ: Matrix metalloproteinase 2 is associated with changes in steroid hormones in the sera and peritoneal fluid of patients with endometriosis. Fertil Steril. 2004, 81: 1235-1239. 10.1016/j.fertnstert.2003.10.027.CrossRefPubMedGoogle Scholar
  20. 20.
    Shimonovitz S, Hurwitz A, Hochner-Celnikier D, Dushnik M, Anteby E, Yagel S: Expression of gelatinase B by trophoblast cells: down-regulation by progesterone. Am J Obstet Gynecol. 1998, 178: 457-461. 10.1016/S0002-9378(98)70420-X.CrossRefPubMedGoogle Scholar
  21. 21.
    Goldman S, Shalev E: Difference in Progesterone Receptor Isoforms Ratio, Between Early and Late First Trimester Human Trophoblast, Is Associated with Differential Cell Invasion and Matrix Metalloproteinase2 (MMP2) Expression. Biol Reprod. 2006, 74: 13-22. 10.1095/biolreprod.105.044925.CrossRefPubMedGoogle Scholar
  22. 22.
    Qin H, Sun Y, Benveniste EN: The transcription factors Sp1, Sp3, and AP-2 are required for constitutive matrix metalloproteinase-2 gene expression in astroglioma cells. J Biol Chem. 1999, 274: 29130-29137. 10.1074/jbc.274.41.29130.CrossRefPubMedGoogle Scholar
  23. 23.
    Mertens PR, Harendza S, Pollock AS, Lovett DH: Glomerular mesangial cell-specific transactivation of matrix metalloproteinase 2 transcription is mediated by YB-1. J Biol Chem. 1997, 272: 22905-22912. 10.1074/jbc.272.36.22905.CrossRefPubMedGoogle Scholar
  24. 24.

Copyright information

© Goldman and Shalev; licensee BioMed Central Ltd. 2006

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Authors and Affiliations

  1. 1.Laboratory for Research in Reproductive Sciences, Department of Obstetrics and GynecologyHa'Emek Medical CenterAfulaIsrael
  2. 2.Rappaport Faculty of MedicineTechnion-Israel Institute of TechnologyHaifaIsrael

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