The influence of estradiol on nervous system function

Drug News and Perspectives

Volumn 18, Issue 10, 2005, Pages 631-637

  Boulware, Marissa I ^a   Mermelstein, Paul G ^a  

^a UNIVERSITY OF MINNESOTA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; ESTRADIOL; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; G PROTEIN COUPLED RECEPTOR; METABOTROPIC RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE;

CELL MEMBRANE; ESTROGEN RESPONSIVE ELEMENT; ESTROGEN SYNTHESIS; GENE ACTIVATION; GENE EXPRESSION; HUMAN; LEARNING; MEMORY; MOOD; MOTOR CONTROL; NERVE EXCITABILITY; NERVOUS SYSTEM FUNCTION; NOCICEPTION; NONHUMAN; REPRODUCTION; REVIEW; SEXUAL MATURATION; SIGNAL TRANSDUCTION; STEROID RELEASE; TRANSCRIPTION REGULATION;

BEHAVIOR; BRAIN; CREB-BINDING PROTEIN; ESTRADIOL; FEMALE; HUMANS; MALE; MODELS, BIOLOGICAL; NERVOUS SYSTEM PHYSIOLOGY; RECEPTORS, ESTROGEN;

EID: 33645054574     PISSN: 02140934     EISSN: None     Source Type: Journal    
DOI: 10.1358/dnp.2005.18.10.959577     Document Type: Review

References (108)

1. Beach, F. Hormones and Behavior. Hoeber, New York, 1948.
2. Couse, J.F. and Korach, K.S. Estrogen receptor null mice: what have we learned and where will they lead us? Endocr Rev 1999, 20: 358-417.
3. Klinge, C.M. Estrogen receptor interaction with estrogen response elements. Nucleic Acids Res 2001, 29: 2905-19.
4. Arnold, A.P. and Breedlove, S.M. Organizational and activational effects of sex steroids on brain and behavior: a reanalysis. Horm Behav 1985, 19: 469-98.
5. Williams, C.L. A reevaluation of the concept of separable periods of organizational and activational actions of estrogens in development of brain and behavior. Ann N Y Acad Sci 1986, 474: 282-92.
6. Pfaff, D.W., Schwartz-Giblin, S., McCarthy, M.M. and Kow, L.-M. Cellular and molecular mechanisms of female reproductive behaviors. Raven Press, Ltd., New York, 1994.
7. Pfaff, D. and Keiner, M. Atlas of estradiol concentrating cells in the central nervous system of the female rat. J Comp Neurol 1973, 151: 121-58.
8. Kuiper, G.G., Enmark, E., Pelto-Huikko, M., Nilsson, S. and Gustafsson, J.A. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci U S A 1996, 93: 5925-30.
9. Tremblay, G.B., Tremblay, A., Copeland, N.G. et al. Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor beta. Mol Endocrinol 1997, 11: 353-65.
10. Shughrue, P.J., Komm, B. and Merchenthaler, I. The distribution of estrogen receptor-beta mRNA in the rat hypothalamus. Steroids 1996, 61: 678-81.
11. Kuiper, G.G. and Gustafsson, J.A. The novel estrogen receptor-beta subtype: potential role in the cell- and promoter-specific actions of estrogens and anti-estrogens. FEBS Lett 1997, 410: 87-90.
12. Kuiper, G.G., Shughrue, P.J., Merchenthaler, I. and Gustafsson, J.A. The estrogen receptor beta subtype: a novel mediator of estrogen action in neuroendocrine systems. Front Neuroendocrinol 1998, 19: 253-86.
13. Laflamme, N., Nappi, R.E., Drolet, G., Labrie, C. and Rivest, S. Expression and neuropeptidergic characterization of estrogen receptors (ERalpha and ERbeta) throughout the rat brain: anatomical evidence of distinct roles of each subtype. J Neurobiol 1998, 36: 357-78.
14. Kastner, P., Krust, A., Turcotte, B. et al. Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. EMBO J 1990, 9: 1603-14.
15. Kraus, W.L., Montano, M.M. and Katzenellenbogen, B.S. Identification of multiple, widely spaced estrogen-responsive regions in the rat progesterone receptor gene. Mol Endocrinol 1994, 8: 952-69.
16. Kushner, P.J., Agard, D.A., Greene, G.L. et al. Estrogen receptor pathways to AP-1. J Steroid Biochem Mol Biol 2000, 74: 311-7.
17. Safe, S. Transcriptional activation of genes by 17 beta-estradiol through estrogen receptor-Sp1 interactions. Vitam Horm 2001, 62: 231-52.
18. Schultz, J.R., Petz, L.N. and Nardulli, A.M. Cell- and ligand-specific regulation of promoters containing activator protein-1 and Sp1 sites by estrogen receptors alpha and beta. J Biol Chem 2005, 280: 347-54.
19. McEwen, B.S. and Alves, S.E. Estrogen actions in the central nervous system. Endocr Rev 1999, 20: 279-307.
20. Nabekura, J., Oomura, Y., Minami, T., Mizuno, Y. and Fukuda, A. Mechanism of the rapid effect of 17 beta-estradiol on medial amygdala neurons. Science 1986, 233: 226-8.
21. Minami, T., Oomura, Y., Nabekura, J. and Fukuda, A. 17 beta-Estradiol depolarization of hypothalamic neurons is mediated by cyclic AMP. Brain Res 1990, 519: 301-7.
22. Aronica, S.M., Kraus, W.L. and Katzenellenbogen, B.S. Estrogen action via the cAMP signaling pathway: stimulation of adenylate cyclase and cAMP-regulated gene transcription. Proc Natl Acad Sci U S A 1994, 91: 8517-21.
23. Zhou, Y., Watters, J.J. and Dorsa, D.M. Estrogen rapidly induces the phosphorylation of the cAMP response element binding protein in rat brain. Endocrinology 1996, 137: 2163-6.
24. Gu, G., Rojo, A.A., Zee, M.C., Yu, J. and Simerly, R.B. Hormonal regulation of CREB phosphorylation in the anteroventral periventricular nucleus. J Neurosci 1996, 16: 3035-44.
25. Watters, J.J., Campbell, J.S., Cunningham, M.J., Krebs, E.G. and Dorsa, D.M. Rapid membrane effects of steroids in neuroblastoma cells: effects of estrogen on mitogen activated protein kinase signalling cascade and c-fos immediate early gene transcription. Endocrinology 1997, 138: 4030-3.
26. Singh, M., Setalo, G., Jr., Guan, X., Warren, M. and Toran-Allerand, C.D. Estrogen-induced activation of mitogen-activated protein kinase in cerebral cortical explants: convergence of estrogen and neurotrophin signaling pathways. J Neurosci 1999, 19: 1179-88.
27. Toran-Allerand, C.D., Singh, M. and Setalo, G., Jr. Novel mechanisms of estrogen action in the brain: new players in an old story. Front Neuroendocrinol 1999, 20: 97-121.
28. Mobbs, C.V., Kaplitt, M., Kow, L.M. and Pfaff, D.W. PLC-alpha: a common mediator of the action of estrogen and other hormones? Mol Cell Endocrinol 1991, 80: C187-91.
29. Qiu, J., Bosch, M.A., Tobias, S.C. et al. Rapid signaling of estrogen in hypothalamic neurons involves a novel G-protein-coupled estrogen receptor that activates protein kinase C. J Neurosci 2003, 23: 9529-40.
30. Chaban, V.V., Lakhter, A.J. and Micevych, P. A membrane estrogen receptor mediates intracellular calcium release in astrocytes. Endocrinology 2004, 145: 3788-95.
31. Weng, G., Bhalla, U.S. and Iyengar, R. Complexity in biological signaling systems. Science 1999, 284: 92-6.
32. Waltereit, R. and Weller, M. Signaling from cAMP/PKA to MAPK and synoptic plasticity. Mol Neurobiol 2003, 27: 99-106.
33. Deisseroth, K., Mermelstein, P.G., Xia, H. and Tsien, R.W. Signaling from synapse to nucleus: the logic behind the mechanisms. Curr Opin Neurobiol 2003, 13: 354-65.
34. Thomas, G.M. and Huganir, R.L. MAPK cascade signalling and synoptic plasticity. Nat Rev Neurosci 2004, 5: 173-83.
35. Wade, C.B. and Dorsa, D.M. Estrogen activation of cyclic adenosine 5′-monophosphate response element-mediated transcription requires the extracellularly regulated kinase/mitogen-activated protein kinase pathway. Endocrinology 2003, 144: 832-38.
36. Lee, S.J., Campomanes, C.R., Sikat, P.T., Greenfield, A.T., Allen, P.B. and McEwen, B.S. Estrogen induces phosphorylation of cyclic AMP response element binding (pCREB) in primary hippocampal cells in a time-dependent manner. Neuroscience 2004, 124: 549-60.
37. Boulware, M.I., Weick, J.P., Becklund, B.R., Kuo, S.P., Groth, R.D. and Mermelstein, P.G. Estradiol activates group I and II metabotropic glutamate receptor signaling, leading to opposing influences on cAMP response element-binding protein. J Neurosci 2005, 25: 5066-78.
38. Szego, C.M. and Pietras, R.J. Biochemical Actions of Hormones. Academic Press, New York, 1981.
39. Razandi, M., Pedram, A., Greene, G.L. and Levin, E.R. Cell membrane and nuclear estrogen receptors (ERs) originate from a single transcript: studies of ERalpha and ERbeta expressed in Chinese hamster ovary cells. Mol Endocrinol 1999, 13: 307-19.
40. Watson, C.S., Campbell, C.H. and Gametchu, B. Membrane oestrogen receptors on rat pituitary tumour cells: immunoidentification and responses to oestradiol and xenoestrogens. Exp Physiol 1999, 84: 1013-22.
41. Wade, C.B., Robinson, S., Shapiro, R.A. and Dorsa, D.M. Estrogen receptor (ER)alpha and ERbeta exhibit unique pharmacologic properties when coupled to activation of the mitogen-activated protein kinase pathway. Endocrinology 2001, 142: 2336-42.
42. Kelly, M.J. and Wagner, E.J. Estrogen modulation of G-protein-coupled receptors. Trends Endocrinol Metab 1999, 10: 369-74.
43. Mermelstein, P.G., Becker, J.B. and Surmeier, D.J. Estradiol reduces calcium currents in rat neostriatal neurons via a membrane receptor. J Neurosci 1996, 16: 595-604.
44. Abraham, I.M., Todman, M.G., Korach, K.S. and Herbison, A.E. Critical in vivo roles for classical estrogen receptors in rapid estrogen actions on intracellular signaling in mouse brain. Endocrinology 2004, 145: 3055-61.
45. Kahlert, S., Nuedling, S., van Eickels, M., Vetter, H., Meyer, R. and Grohe, C. Estrogen receptor alpha rapidly activates the IGF-1 receptor pathway. J Biol Chem 2000, 275: 18447-53.
46. Razandi, M., Pedram, A., Park, S.T. and Levin, E.R. Proximal events in signaling by plasma membrane estrogen receptors. J Biol Chem 2003, 278: 2701-12.
47. Chambliss, K.L., Yuhanna, I.S., Mineo, C. et al. Estrogen receptor alpha and endothelial nitric oxide synthase are organized into a functional signaling module in caveolae. Circ Res 2000, 87: E44-52.
48. Wyckoff, M.H., Chambliss, K.L., Mineo, C. et al. Plasma membrane estrogen receptors are coupled to endothelial nitric-oxide synthase through Galpha(i). J Biol Chem 2001, 276: 27071-6.
49. Razandi, M., Oh, P., Pedram, A., Schnitzer, J. and Levin, E.R. ERs associate with and regulate the production of caveolin: implications for signaling and cellular actions. Mol Endocrinol 2002, 16: 100-15.
50. Burgueno, J., Enrich, C., Canela, E.I. et al. Metabotropic glutamate type 1α receptor localizes in low-density caveolin-rich plasma membrane fractions. J Neurochem 2003, 86: 785-91.
51. Burgueno, J., Canela, E.I., Mallol, J., Lluis, C., Franco, R. and Ciruela, F. Mutual regulation between metabotropic glutamate type 1alpha receptor and caveolin proteins: from traffick to constitutive activity. Exp Cell Res 2004, 300: 23-34.
52. Gu, Q. and Moss, R.L. 17 beta-Estradiol potentiates kainate-induced currents via activation of the cAMP cascade. J Neurosci 1996, 16: 3620-9.
53. Lagrange, A.H., Ronnekleiv, O.K. and Kelly, M.J. Modulation of G protein-coupled receptors by an estrogen receptor that activates protein kinase A. Mol Pharmacol 1997, 51: 605-12.
54. Kelly, M.J., Lagrange, A.H., Wagner, E.J. and Ronnekleiv, O.K. Rapid effects of estrogen to modulate G protein-coupled receptors via activation of protein kinase A and protein kinase C pathways. Steroids 1999, 64: 64-75.
55. Beyer, C. and Karolczak, M. Estrogenic stimulation of neunte growth in midbrain dopaminergic neurons depends on cAMP/protein kinase A signalling. J Neurosci Res 2000, 59: 107-16.
56. Azcoitia, I., Sierra, A. and Garcia-Segura, L.M. Localization of estrogen receptor beta-immunoreactivity in astrocytes of the adult rat brain. Glia 1999, 26: 260-7.
57. Compagnone, N.A. and Mellon, S.H. Neurosteroids: biosynthesis and function of these novel neuromodulators. Front Neuroendocrinol 2000, 21: 1-56.
58. Garcia-Segura, L.M., Azcoitia, I. and DonCarlos, L.L. Neuroprotection by estradiol. Prog Neurobiol 2001, 63: 29-60.
59. Wehrenberg, U., Prange-Kiel, J. and Rune, G.M. Steroidogenic factor-1 expression in marmoset and rat hippocampus: co-localization with StAR and aromatase. J Neurochem 2001,76: 1879-86.
60. Prange-Kiel, J., Wehrenberg, U., Jarry, H. and Rune, G.M. Para/autocrine regulation of estrogen receptors in hippocampal neurons. Hippocampus 2003, 13: 226-34.
61. Amateau, S.K., Alt, J.J., Stamps, C.L. and McCarthy, M.M. Brain estradiol content in newborn rats: sex differences, regional het erogeneity, and possible de novo synthesis by the female telencephalon. Endocrinology 2004, 145: 2906-17.
62. Hojo, Y., Hattori, T.A., Enami, T. et al. Adult male rat hippocampus synthesizes estradiol from pregnenolone by cytochromes P45Q17alpha and P450 aromatase localized in neurons. Proc Natl Acad Sci U S A 2004, 101: 865-70.
63. Kretz, O., Fester, L., Wehrenberg, U. et al. Hippocampal synapses depend on hippocampal estrogen synthesis. J Neurosci 2004, 24: 5913-21.
64. Toran-Allerand, C.D., Tinnikov, A.A., Singh, R.J. and Nethrapalli, I.S. 17alpha-estradiol: a brain-active estrogen? Endocrinology 2005, 146: 3843-50.
65. Toran-Allerand, C.D., Guan, X., MacLusky, N.J. et al. ER-X: a novel, plasma membrane-associated, putative estrogen receptor that is regulated during development and after ischemic brain injury. J Neurosci 2002, 22: 8391-401.
66. Singh, M., Setalo, G., Jr., Guan, X., Frail, D.E. and Toran-Allerand, C.D. Estrogen-induced activation of the mitogen-activated protein kinase cascade in the cerebral cortex of estrogen receptor-alpha knock-out mice. J Neurosci 2000, 20: 1694-700.
67. Toran-Allerand, C.D. Estrogen and the Brain: Beyond ER-alpha, ER-beta, and 17beta-estradiol. Ann N Y Acad Sci 2005, 1052: 136-44.
68. Bryant, D.N., Bosch, M.A., Ronnekleiv, O.K. and Dorsa, D.M. 17-beta Estradiol rapidly enhances extracellular signal-regulated kinase 2 phosphorylation in the rat brain. Neuroscience 2005, 133: 343-52.
69. Abraham, I.M. and Herbison, A.E. Major sex differences in non-genomic estrogen actions on intracellular signaling in mouse brain in vivo. Neuroscience 2005, 131: 945-51.
70. MacLusky, N.J., Luine, V.N., Hajszan, T. and Leranth, C. The 17alpha and 17beta isomers of estradiol both induce rapid spine synapse formation in the CA1 hippocampal subfield of ovariectomized female rats. Endocrinology 2005, 146: 287-93.
71. Gould, E., Woolley, C.S., Frankfurt, M. and McEwen, B.S. Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood. J Neurosci 1990, 10: 1286-91.
72. Woolley, C.S. and McEwen, B.S. Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat. J Neurosci 1992, 12: 2549-54.
73. Woolley, C.S. and McEwen, B.S. Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat. J Comp Neurol 1993, 336: 293-306.
74. Wong, M. and Moss, R.L. Long-term and short-term electrophysiological effects of estrogen on the synoptic properties of hippocampal CA1 neurons. J Neurosci 1992, 12: 3217-25.
75. Weiland, N.G. Estradiol selectively regulates agonist binding sites on the N-methyl-D-aspartate receptor complex in the CA1 region of the hippocampus. Endocrinology 1992, 131: 662-8.
76. Woolley, C.S., Weiland, N.G., McEwen, B.S. and Schwartzkroin, P.A. Estradiol increases the sensitivity of hippocampal CA1 pyramidal cells to NMDA receptor-mediated synoptic input: correlation with dendritic spine density. J Neurosci 1997, 17: 1848-59.
77. Cordoba Montoya, D.A. and Carrer, H.F. Estrogen facilitates induction of long term potentiation in the hippocampus of awake rats. Brain Res 1997, 778: 430-8.
78. Foy, M.R., Xu, J., Xie, X., Brinton, R.D., Thompson, R.F. and Berger, T.W. 17beta-Estradiol enhances NMDA receptor-mediated EPSPs and long-term potentiation. J Neurophysiol 1999, 81: 925-9.
79. Kim, J.S., Kim, H.Y., Kim, J.H. et al. Enhancement of rat hippocampal long-term potentiation by 17 beta-estradiol involves mitogen-activated protein kinase-dependent and -independent components. Neurosci Lett 2002, 332: 65-9.
80. Smith, C.C. and McMahon, L.L. Estrogen-induced increase in the magnitude of long-term potentiation occurs only when the ratio of NMDA transmission to AMPA transmission is increased. J Neurosci 2005, 25: 7780-91.
81. Vouimba, R.M., Foy, M.R., Foy, J.G. and Thompson, R.F. 17beta-Estradiol suppresses expression of long-term depression in aged rats. Brain Res Bull 2000, 53: 783-7.
82. Zamani, M.R., Desmond, N.L. and Levy, W.B. Estradiol modulates long-term synaptic depression in female rat hippocampus. J Neurophysiol 2000, 84: 1800-8.
83. Desmond, N.L., Zhang, D.X. and Levy, W.B. Estradiol enhances the induction of homosynaptic long-term depression in the CA1 region of the adult, ovariectomized rat. Neurobiol Learn Mem 2000, 73: 180-7.
84. Shiroma, S., Yamaguchi, T. and Kometani, K. Effects of 17beta-estradiol on chemically induced long-term depression. Neuropharmacology 2005, 49: 97-102.
85. Solum, D.T. and Handa, R.J. Estrogen regulates the development of brain-derived neurotrophic factor mRNA and protein in the rat hippocampus. J Neurosci 2002, 22: 2650-9.
86. Wu, T.W., Wang, J.M., Chen, S. and Brinton, R.D. 17beta-Estradiol induced Ca2+ influx via L-type calcium channels activates the Src/ERK/cyclic-AMP response element binding protein signal pathway and BCL-2 expression in rat hippocampal neurons: A potential initiation mechanism for estrogen-induced neuroprotection. Neuroscience 2005, 135: 59-72.
87. Zhao, L., Chen, S., Ming Wang, J. and Brinton, R.D. 17beta-Estradiol induces Ca2+ influx, dendritic and nuclear Ca2+ rise and subsequent cyclic AMP response element-binding protein activation in hippocampal neurons: a potential initiation mechanism for estrogen neurotrophism. Neuroscience 2005, 132: 299-311.
88. Williams, C.L. Estrogen effects on cognition across the lifespan. Horm Behav 1998, 34: 80-4.
89. Dohanich, G.P. Gonadal steroids, learning and memory. Academic Press, San Diego, 2002.
90. Henderson, V.W., Paganini-Hill, A., Emanuel, C.K., Dunn, M.E. and Buckwalter, J.G. Estrogen replacement therapy in older women. Comparisons between Alzheimer's disease cases and nondemented control subjects. Arch Neurol 1994, 51: 896-900.
91. Paganini-Hill, A. and Henderson, V.W. Estrogen replacement therapy and risk of Alzheimer disease. Arch Intern Med 1996, 156: 2213-7.
92. Tang, M.X., Jacobs, D., Stern, Y. et al. Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet 1996, 348: 429-32.
93. Kawas, C., Resnick, S., Morrison, A. et al. A prospective study of estrogen replacement therapy and the risk of developing Alzheimer's disease: the Baltimore Longitudinal Study of Aging. Neurology 1997, 48: 1517-21.
94. Ivey, M.E. and Bardwick, J.M. Patterns of affective fluctuation in the menstrual cycle. Psychosom Med 1968, 30: 336-45.
95. May, R.R. Mood shifts and the menstrual cycle. J Psychosom Res 1976, 20: 125-30.
96. Becker, D., Creutzfeldt, O.D., Schwibbe, M. and Wuttke, W. Changes in physiological, EEG and psychological parameters in women during the spontaneous menstrual cycle and following oral contraceptives. Psychoneuroendocrinology 1982, 7: 75-90.
97. Hampson, E. and Kimura, D. Reciprocal effects of hormonal fluctuations on human motor and perceptual-spatial skills. Behav Neurosci 1988, 102: 456-9.
98. Hampson, E. Estrogen-related variations in human spatial and articulatory-motor skills. Psychoneuroendocrinology 1990, 15: 97-111.
99. Riley, J.L., 3rd, Robinson, M.E., Wise, E.A. and Price, D.D. A meta-analytic review of pain perception across the menstrual cycle. Pain 1999, 81: 225-35.
100. Frick, K.M., Fernandez, S.M. and Bulinski, S.C. Estrogen replacement improves spatial reference memory and increases hippocampal synaptophysin in aged female mice. Neuroscience 2002, 115: 547-58.
101. Becker, J.B., Snyder, P.J., Miller, M.M., Westgate, S.A. and Jenuwine, M.J. The influence of estrous cycle and intrastriatal estradiol on sensorimotor performance in the female rat. Pharmacol Biochem Behav 1987, 27: 53-9.
102. Smith, M.J., Adams, L.F., Schmidt, P.J., Rubinow, D.R. and Wassermann, E.M. Effects of ovarian hormones on human cortical excitability. Ann Neurol 2002, 51: 599-603.
103. Stoffel, E.C., Ulibarri, C.M. and Craft, R.M. Gonadal steroid hormone modulation of nociception, morphine antinociception and reproductive indices in male and female rats. Pain 2003, 103: 285-302.
104. Ji, R.R., Kohno, T., Moore, K.A. and Woolf, C.J. Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci 2003, 26: 696-705.
105. Lonze, B.E. and Ginty, D.D. Function and regulation of CREB family transcription factors in the nervous system. Neuron 2002, 35: 605-23.
106. Murphy, D.D. and Segal, M. Morphological plasticity of dendritic spines in central neurons is mediated by activation of cAMP response element binding protein. Proc Natl Acad Sci U S A 1997, 94: 1482-7.
107. Vasudevan, N., Kow, L.M. and Pfaff, D.W. Early membrane estrogenic effects required for full expression of slower genomic actions in a nerve cell line. Proc Natl Acad Sci U S A 2001, 98: 12267-71.
108. Kow, L.M. and Pfaff, D.W. The membrane actions of estrogens can potentiate their lordosis behavior-facilitating genomic actions. Proc Natl Acad Sci U S A 2004, 101: 12354-7.