Pérez-Rivero JJ, Aguilar-Setién A, Villa-Godoy A, Serrano H

Idioma: Español/Inglés
Referencias bibliográficas: 49
Paginas: 437-452
Archivo PDF: 575.28 Kb.

RESUMEN

La exquisita regulación de la función ejercida por los estrógenos en diversos aspectos de la reproducción animal, se debe básicamente a los receptores con los que interactúan en los órganos blanco. El uso de técnicas moleculares bioquímicas y de genética ha permitido dilucidar la estructura modular de los receptores nucleares, entre los que se encuentran los estrogénicos. Cada módulo del receptor tiene características estructurales particulares que le permiten interactuar con una diversidad de moléculas. Como resultado de la interacción entre el receptor y diversas moléculas, desencadena efectos tan diferentes como una inhibición de la acción hormonal, hiperactivación de ésta, reflejada en el aumento en la tasa de trascripción de genes específicos o, incluso, reacciones inesperadas resultantes de la interacción con compuestos sintéticos que presentan una estructura tridimensional reconocible por el receptor. Con esta interacción se puede alterar la propia estructura tridimensional del receptor, permitiéndole ejercer funciones no descritas en los artículos recapitulativos clásicos. En esta revisión hemos establecido una correlación entre la estructura, función y regulación de los receptores nucleares, en especial, los estrogénicos, para ofrecer de manera accesible estos aspectos.

REFERENCIAS (EN ESTE ARTÍCULO)

1. Egea PF, Klaholz BP, Moras D. Ligand protein interactions in nuclear receptor hormones. FEBS Lett 2000; 476: 62-67

2. Heinlein CA, Chang C. Androgen receptor (AR) coregulators: An Overview. Endocr Rev 2002; 23: 175-200.

3. DeFranco DB. Navigating steroid hormone receptors through the nuclear compartment. Mol Endocrinol 2002; 16:1449-1455

4. Nadal A, Ropero AB, Fuentes E , Soria B. The plasma membrane estrogen receptor: nuclear or unclear? Trends Pharmacol Sci 2001; 22: 597- 599

5. Cowley SM, Parker MG. A comparison of transcriptional activation by ER and ER . J Steroid Biochem Mol Biol 1999;69:165-175

6. Bunone G, Briand PA,Miksicek RJ, Picard D. Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation. EMBO J 1996;15:2174-2183.

7. Freedman LP. Anatomy of the steroid receptor zink finger region. Endocr Rev 1992; 13: 129-145.

8. Black BE, Holaska JM, Rastinejad F, Paschal BM. DNA binding domains in diverse nuclear receptor function as nuclear export signal. Curr Biol 2001; 11: 1749-1758

9. Bapat AR, Frail DE. Full-length estrogen receptor and its ligand-binding domain adopt different conformations upon binding ligand. J Steroid Biochem Mol Biol 2003; 86:143-149.

10. Onate SA, Boonyaratanakornkit V, Spencer TE, Tsai SY, Tsai M, Edwards DP et al. The steroid receptor coactivator-1 contains multiple receptor interacting and activation domains that cooperatively enhance the activation function 1 (AF1) and AF2 domains of steroid receptors. J Biol Chem 1998;279 :12101-12108.

11. Weihua Z, Andersson S, Cheng G, Simpson ER, Warner M, Gustafsson J. Update on estrogen signaling. FEBS Lett 2003 ; 546:17-24.

12. Mosselman J, Polman R. Dijkema, ER: identification and characterization of a novel human estrogen receptor. FEBS lett 1996;392: 49-53.

13. Westin S, Kurokawa R, Nolte RT, Wisely GB, McInerney EM, Rose DW, et al. Interactions controlling the assembly of nuclear receptor heterodimers and co-activators. Nature 1998;395:199-202.

14. Brozozowski AM, Pike AC, Dauter Z, Hubbard RD, Bonn T,Engström O et al. Mollecular basis of agonism and antagonism in the estrogen receptor. Nature 1977;389:753-758.

15. Hu X, Lazar MA. The CoRNR motif controls.The recruitment of corepressors by nuclear hormone receptors. Nature 1999;402:93-96

16. Nillson S, Mäkelä S, Treuter E, Tujague M, Thomsen J, Anderson G et al. Mechanisms of estrogen action. Physiol Rev 2001;81:1535-1565.

17. Montano MM, Müller V, Trobaugh A, Katzenellenbogen BS. The carboxyterminal F domain of the human estrogen receptor: role in the transcriptional activity of the receptor and the effectiveness of antiestrogens as estrogen antagonists. Mol Endocrinol 1995;9:814- 825.

18. Knoblauch R, Garabedian MJ. Role for Hsp90-Asociated cochaperone p23 in estrogen receptor signal transduction. Mol Cell Biol 1999;19:3748-3759.

19. Klinge CM. Estrogen receptor interaction with co-activators and co-repressors. Steroids 2000; 65:227-251.

20. Forbes DJ. Structure and function of the nuclear pore complex. Annu Rev Cell Biol 1992; 8:495-527.

21. Aronica SM, Katzenellenbogen BS. Stimulation of estrogen receptor-mediated transcription and alteration in the phosphorylation state of the rat uterine estrogen receptor by estrogen, cyclic adenosine monophosphate, and insulin-like growth factor-I. Mol Endocrinol 1993;7:743-752.

22. Arnold SF, Obourn JD, Jaffe H, Notides AC. Phosphorylation of the human estrogen receptor on tyrosine 537 in vivo and by src family tyrosine kinases in vivo. Mol Endocrinol 1995;9:24-33.

23. LeGoff P, Montano MM, Schodin DJ, Katze-nellenbogen BS. Phosphorylation of the human estrogen receptor. Identification of hormone-regulated sites and examination of their influence on transcrip-tional activity. J Biol Chem 1994;269:4458-4466.

24. Arnold SF, Obourn JD, Jaffe H, Notides AC. Phosphorylation of the human estrogen receptor by mitogen-activated protein kinase and casein kinase II: consequence DNA binding. J Steroid Biochem Mol Biol 1995;55:163-172.

25. Ignar-Trowbridge DM, Pimentel M, Parker MG, McLachlan JA, Korach KS. Peptide growth factor cross-talk with the estrogen receptor requires the A/B domain and occurs independently of protein kinase C or estradiol. Endocrinology 1996;137:1735-1744.

26. Trowbridge JM, Rogatsky I, Garabedian MJ. Regulation of estrogen receptor transcriptional enhancement by the cyclin A/Cdk2 complex. Proc Natl Acad Sci USA. 1997;94:10132-10137.

27. Maniatis T, Reed R. An extensive network of coupling among gene expression machines. Nature 2002; 416:499-506.

28. Hewitt SC, Korach KS. Oestrogen receptor knockout mice: roles for estrogen receptors and in reproductive tissues. Reproduction 2003 ; 125 : 143-149.

29. Levin ER. Genome and hormones: Gender differences in physiology. Invited Review: Cell localization, physiology and nongenomic actions of estrogen receptors. J Appl Physiol 2001;91:1860-1867.

30. Maniatis T, Tasic B. Alternative pre-mRNA splicing and proteome expansion in metazoas. Nature 2002;418:236-243.

31. Ogawa S, Inoue S, Watanabe T, Orimo A, Hosoi T, Ouchi Y et al. Molecular cloning and characterization of human estrogen receptor?: a potential inhibitor of estrogen action in human. Nucleic Acid Res 1998;26:3505-3512.

32. Cowley SM, Hoare S, Mosselman S, Parker MG. Estrogen receptor and form heterodimers an DNA. J Biol Chem 1997;272:19858-19862.

33. Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci U S A 1996; 93: 5925-5930.

34. Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT et al. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 1998;139: 4252-4263.

35. Fasor J, Barnett DH, Danes JM, Hess R, Parlow AF, Katzenellenbogen BS. Response-specific and ligand dose-dependent modulation of estrogen receptor (ER) activity by ER in the uterus. Endocrinology 2003; 144 : 3159-3166.

36. Weihua Z, Saji S, Makinen S, Cheng G, Jensen EV, Warner M et al. Estrogen receptor (ER) beta, a modulator of ER alpha in the uterus. Proc Natl Acad Sci U S A 2000;97: 5936-5941

37. Hess RA, Bunick D, Lee K, Bahr J, Taylor JA, Korach KS et al. A role for oestrogens in the male reproductive system. Nature 1997;390: 509-511

38. Lee K, Jessop H, Suswillo R, Zaman G, Lanyon L. Bone adaptation requires oestrogen receptor. Nature 2003; 424: 389.

39. Vasudevan N, Ogawa S, Pfaff D. Estrogen and thyroid hormone receptor interactions: Physiological flexibility by molecular specificity. Physiol Rev 2002;82:923-944.

40. Rodriguez-Medina MA, Reyes A, Chavarria ME, Vergara-Onofre M, Canchola E, Rosado A. Asymmetric calmodulin distribution in the hypothalamus: role of sexual differentiation in the rat. Pharmacol Biochem Behav 2000; 72:189-195.

41. Wang L, Andersson S, Warner M, Gustafsson JA. Morphological abnormalities in the brains of estrogen receptor beta knockout mice. Proc Natl Acad Sci U S A 2001; 98:2792-2796.

42. Pare G, Krust A, Karas RH, Dupont S, Arnovitz M, Chambon P et al. Estrogen receptor- mediates the protective effect of estrogen against vascular injury. Circ Res. 2002;90:1087-1092.

43. Luconi M, Forti G, Baldi E. Genomic and nongenomic effects of estrogens:molecular mechanisms of action and clinical implications for male reproduction. J Steroid Biochem Mol Biol 2002;80: 369-381.

44. Moggs JG, Orphanides G. Estrogen receptors: orchestators of pleiotropic cellular responses. EMBO rep 2001;2:775-781.

45. Ho KJ, Liao JK. Non-nuclear actions of estrogen: New targets for prevention and treatment of cardiovascular disease. Mol interv 2002; 2:219-228.

46. Wong C, McNally C, Nickbarg E, KommBS, Cheskis B. Estrogen receptor-interacting protein that modulates its nongenomic activity-crosstalk with Src/Erk phosphorylation cascade. Proc Natl Acad Sci USA 2002;99:14783-14788.

47. Khosla S. Estrogen, selective estrogen receptor modulators and now mechanism-specific ligands of the estrogen or androgen receptor? Trend Pharmacol Sci 2003;24:261-263.

48. Macgregor JI, Jordan VC. Basic guide to the mecha-nism of antiestrogen action. Pharmacol Rev 1998;50:151-196.

49. Delmas PD, Bjarnason NH, Mitlak BH et al. Effects of raloxifene on body mineral density, serum cholesterol concentrations and uterine endometrium in postmenopausal women. N Engl J Med 1997; 337: 1641-1647.