Advertisement

Local Production of Estrogen and its Rapid Modulatory Action on Synaptic Plasticity

  • Suguru Kawato
  • Yasushi Hojo
  • Hideo Mukai
  • Gen Murakami
  • Mari Ogiue-Ikeda
  • Hirotaka Ishii
  • Tetsuya Kimoto

It has long been a common sense that sex hormones are synthesized in the gonads, and reach the brain via the blood circulation. In contrast with this view, the authors demonstrate that estrogen and androgen are also synthesized locally in the hippocampus of adult animals, from cholesterol through dehydroepiandrosterone in hippocampal neurons. These neurosteroids are synthesized by cytochrome P450s and hydroxysteroid dehydrogenases and 5α-reductase. The expression levels of enzymes are as low as 1/200–1/50,000 of those in endocrine organs, preventing quantitative investigations. Localization of P450(17α) and P450arom is observed in synapses of principal glutamatergic neurons, in addition to endoplasmic reticulum, suggesting synaptocrine machanisms.

Because several nanomolar estrogen and androgen are observed in the hippocampus, they are expected to have physiological functions. Estrogen modulates memory-related synaptic plasticity not only slowly, but also rapidly in the hippocampus. Molecular mechanisms of rapid action via membrane receptors have not been well elucidated in comparison with those of delayed action via genomic processes. We here describe rapid modulation of representative synaptic plasticity, i.e., long-term depression (LTD), long-term potentiation (LTP) and spinogenesis, by 17β-estradiol, selective estrogen agonists.

We demonstrate that 1–10 nM estradiol induced rapid enhancement of LTD within 1 h in CA1, CA3 and dentate gyrus (DG). On the other hand, the modulation of LTP by estradiol is not statistically significant. The total density of spines is increased in CA1 pyramidal neurons, within 2 h after application of estradiol. The total density of thorns (postsynaptic spine-like structure) is, however, decreased by estradiol in CA3 pyramidal neurons. Both the increase of spines in CA1 and the decrease of thorns in CA3 are driven by Erk MAP kinase. Only agonist of estrogen receptor ERalpha induces the same enhancement/suppression effect as estradiol on both LTD and spinogenesis in CA1 and CA3. ERbeta agonist induces completely different results.

Estrogen receptor ERalpha localizes in spines and presynapses of principal glutamatergic neurons in CA1, CA3 and DG. The same ERalpha is also located in nuclei. Identification of ERalpha is successfully performed using purified RC-19 antibody. Attention must be paid to the fact that non-purified ERalpha antisera often react significantly with unknown proteins, resulting in wrong staining different from real ERalpha distribution. Identification of kinases/phosphatases in downstream of ERalpha as well as other synaptic estrogen receptors is essential to advance the field.

Keywords

Estradiol estrogen androgen neurosteroid synaptic plasticity estrogen receptor hippocampus LTP LTD 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Kimoto T, Tsurugizawa T, Ohta Y, et al. Neurosteroid synthesis by cytochrome p450-containing systems localized in the rat brain hippocampal neurons: N-methyl-D-aspartate and calcium-dependent synthesis. Endocrinology 2001; 142:3578–3589.PubMedCrossRefGoogle Scholar
  2. 2.
    Kawato S, Hojo Y, Kimoto T. Histological and metabolism analysis of P450 expression in the brain. Methods Enzymol 2002; 357:241–249.PubMedCrossRefGoogle Scholar
  3. 3.
    Kawato S, Yamada M, Kimoto T. Brain neurosteroids are 4th generation neuromessengers in the brain: cell biophysical analysis of steroid signal transduction. Adv Biophys 2003; 37:1–48.PubMedCrossRefGoogle Scholar
  4. 4.
    Hojo Y, Hattori TA, Enami T, et al. Adult male rat hippocampus synthesizes estradiol from pregnenolone by cytochromes P45017alpha and P450 aromatase localized in neurons. Proc Natl Acad Sci USA 2004; 101:865–870.PubMedCrossRefGoogle Scholar
  5. 5.
    Kretz O, Fester L, Wehrenberg U, et al. Hippocampal synapses depend on hippocampal estrogen synthesis. J Neurosci 2004; 24:5913–5921.PubMedCrossRefGoogle Scholar
  6. 6.
    Baulieu EE. Neurosteroids: of the nervous system, by the nervous system, for the nervous system. Recent Prog Horm Res 1997; 52:1–32.PubMedGoogle Scholar
  7. 7.
    Corpechot C, Robel P, Axelson M, et al. Characterization and measurement of dehydroepiandrosterone sulfate in rat brain. Proc Natl Acad Sci USA 1981; 78:4704–4707.PubMedCrossRefGoogle Scholar
  8. 8.
    Robel P, Bourreau E, Corpechot C, et al. Neuro-steroids: 3 beta-hydroxy-delta 5-derivatives in rat and monkey brain. J Steroid Biochem 1987; 27:649–655.PubMedCrossRefGoogle Scholar
  9. 9.
    Warner M, Gustafsson JA. Cytochrome P450 in the brain: neuroendocrine functions. Front Neuroendocrinol 1995; 16:224–236.PubMedCrossRefGoogle Scholar
  10. 10.
    Baulieu EE, Robel P. Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) as neuroactive neurosteroids. Proc Natl Acad Sci USA 1998; 95:4089–4091.PubMedCrossRefGoogle Scholar
  11. 11.
    Le Goascogne C, Sananes N, Gouezou M, et al. Immunoreactive cytochrome P-450(17 alpha) in rat and guinea-pig gonads, adrenal glands and brain. J Reprod Fertil 1991; 93:609–622.PubMedGoogle Scholar
  12. 12.
    Mellon SH, Deschepper CF. Neurosteroid biosynthesis: genes for adrenal steroidogenic enzymes are expressed in the brain. Brain Res 1993; 629:283–292.PubMedCrossRefGoogle Scholar
  13. 13.
    Bi R, Broutman G, Foy MR, et al. The tyrosine kinase and mitogen-activated protein kinase pathways mediate multiple effects of estrogen in hippocampus. Proc Natl Acad Sci USA 2000; 97:3602–3607.PubMedCrossRefGoogle Scholar
  14. 14.
    Foy MR, Xu J, Xie X, et al. 17beta-estradiol enhances NMDA receptor-mediated EPSPs and long-term potentiation. J Neurophysiol 1999; 81:925–929.PubMedGoogle Scholar
  15. 15.
    Pozzo-Miller LD, Inoue T, Murphy DD. Estradiol increases spine density and NMDA-dependent Ca2+ transients in spines of CA1 pyramidal neurons from hippocampal slices. J Neurophysiol 1999; 81:1404–1411.PubMedGoogle Scholar
  16. 16.
    Shibuya K, Takata N, Hojo Y, et al. Hippocampal cytochrome P450s synthesize brain neurosteroids which are paracrine neuromodulators of synaptic signal transduction. Biochim Biophys Acta 2003; 1619:301–316.PubMedGoogle Scholar
  17. 17.
    Woolley CS. Estrogen-mediated structural and functional synaptic plasticity in the female rat hippocampus. Horm Behav 1998; 34:140–148.PubMedCrossRefGoogle Scholar
  18. 18.
    Woolley CS, McEwen BS. Estradiol regulates hippocampal dendritic spine density via an N-methyl-D-aspartate receptor-dependent mechanism. J Neurosci 1994; 14:7680–7687.PubMedGoogle Scholar
  19. 19.
    Sanne JL, Krueger KE. Expression of cytochrome P450 side-chain cleavage enzyme and 3 beta-hydroxysteroid dehydrogenase in the rat central nervous system: a study by polymerase chain reaction and in situ hybridization. J Neurochem 1995; 65:528–536.PubMedCrossRefGoogle Scholar
  20. 20.
    Murakami G, Tanabe N, Ishii HT, et al. Role of cytochrome p450 in synaptocrinology: endogenous estrogen synthesis in the brain hippocampus. Drug Metab Rev 2006; 38:353–369.PubMedCrossRefGoogle Scholar
  21. 21.
    Furukawa A, Miyatake A, Ohnishi T, Ichikawa Y. Steroidogenic acute regulatory protein (StAR) transcripts constitutively expressed in the adult rat central nervous system: colocalization of StAR, cytochrome P-450SCC (CYP XIA1), and 3beta-hydroxysteroid dehydrogenase in the rat brain. J Neurochem 1998; 71:2231–2238.PubMedGoogle Scholar
  22. 22.
    King SL, Marks MJ, Grady SR, et al. Conditional expression in corticothalamic efferents reveals a developmental role for nicotinic acetylcholine receptors in modulation of passive avoidance behavior. J Neurosci 2003; 23:3837–3843.PubMedGoogle Scholar
  23. 23.
    Zwain IH, Yen SS. Neurosteroidogenesis in astrocytes, oligodendrocytes, and neurons of cerebral cortex of rat brain. Endocrinology 1999; 140:3843–3852.PubMedCrossRefGoogle Scholar
  24. 24.
    Zwain IH, Yen SS. Dehydroepiandrosterone: biosynthesis and metabolism in the brain. Endocrinology 1999; 140:880–887.PubMedCrossRefGoogle Scholar
  25. 25.
    Compagnone NA, Bulfone A, Rubenstein JL, Mellon SH. Steroidogenic enzyme P450c17 is expressed in the embryonic central nervous system. Endocrinology 1995; 136:5212–5223.PubMedCrossRefGoogle Scholar
  26. 26.
    Wehrenberg U, Prange-Kiel J, Rune GM. Steroidogenic factor-1 expression in marmoset and rat hippocampus: co-localization with StAR and aromatase. J Neurochem 2001; 76:1879–1886.PubMedCrossRefGoogle Scholar
  27. 27.
    Ivanova T, Beyer C. Ontogenetic expression and sex differences of aromatase and estrogen receptor-alpha/beta mRNA in the mouse hippocampus. Cell Tissue Res 2000; 300:231–237.PubMedCrossRefGoogle Scholar
  28. 28.
    Beyenburg S, Watzka M, Blumcke I, et al. Expression of mRNAs encoding for 17beta-hydroxisteroid dehydrogenase isozymes 1, 2, 3 and 4 in epileptic human hippocampus. Epilepsy Res 2000; 41:83–91.PubMedCrossRefGoogle Scholar
  29. 29.
    Jung-Testas I, Hu ZY, Baulieu EE, Robel P. Neurosteroids: biosynthesis of pregnenolone and progesterone in primary cultures of rat glial cells. Endocrinology 1989; 125:2083–2091.PubMedCrossRefGoogle Scholar
  30. 30.
    Koenig HL, Schumacher M, Ferzaz B, et al. Progesterone synthesis and myelin formation by Schwann cells. Science 1995; 268:1500–1503.PubMedCrossRefGoogle Scholar
  31. 31.
    Tsutsui K, Ukena K, Usui M, et al. Novel brain function: biosynthesis and actions of neurosteroids in neurons. Neurosci Res 2000; 36:261–273.PubMedCrossRefGoogle Scholar
  32. 32.
    Jakab RL, Horvath TL, Leranth C, et al. Aromatase immunoreactivity in the rat brain: gonadectomy-sensitive hypothalamic neurons and an unresponsive “limbic ring” of the lateral septum-bed nucleus-amygdala complex. J Steroid Biochem Mol Biol 1993; 44:481–498.PubMedCrossRefGoogle Scholar
  33. 33.
    Shinzawa K, Ishibashi S, Murakoshi M, et al. Relationship between zonal distribution of microsomal cytochrome P-450s (P-450(17) alpha, lyase and P-450C21) and steroidogenic activities in guinea-pig adrenal cortex. J Endocrinol 1988; 119:191–200.PubMedCrossRefGoogle Scholar
  34. 34.
    Le Goascogne C, Robel P, Gouezou M, et al. Neurosteroids: cytochrome P-450scc in rat brain. Science 1987; 237:1212–1215.PubMedCrossRefGoogle Scholar
  35. 35.
    Mensah-Nyagan AG, Do-Rego JL, Beaujean D, et al. Neurosteroids: expression of steroidogenic enzymes and regulation of steroid biosynthesis in the central nervous system. Pharmacol Rev 1999; 51:63–81.PubMedGoogle Scholar
  36. 36.
    Kibaly C, Patte-Mensah C, Mensah-Nyagan AG. Molecular and neurochemical evidence for the biosynthesis of dehydroepiandrosterone in the adult rat spinal cord. J Neurochem 2005; 93:1220–1230.PubMedCrossRefGoogle Scholar
  37. 37.
    Wang MD, Wahlstrom G, Backstrom T. The regional brain distribution of the neurosteroids pregnenolone and pregnenolone sulfate following intravenous infusion. J Steroid Biochem Mol Biol 1997; 62:299–306.PubMedCrossRefGoogle Scholar
  38. 38.
    Kawato S, Ogiue-Ikeda M, Tanabe N, et al. Rapid modlulation of long-term depression and spinogenesis by endocrine disrupters in adult rat hippocampus. In 4th International Meeting Steroids and Nerbous System. Torino, 2007.Google Scholar
  39. 39.
    Liu S, Sjovall J, Griffiths WJ. Neurosteroids in rat brain: extraction, isolation, and analysis by nanoscale liquid chromatography-electrospray mass spectrometry. Anal Chem 2003; 75:5835–5846.PubMedCrossRefGoogle Scholar
  40. 40.
    Higashi T, Sugitani H, Yagi T, Shimada K. Studies on neurosteroids XVI. Levels of pregnenolone sulfate in rat brains determined by enzyme-linked immunosorbent assay not requiring solvolysis. Biol Pharm Bull 2003; 26:709–711.PubMedCrossRefGoogle Scholar
  41. 41.
    Liere P, Akwa Y, Weill-Engerer S, et al. Validation of an analytical procedure to measure trace amounts of neurosteroids in brain tissue by gas chromatography-mass spectrometry. J Chromatogr B Biomed Sci Appl 2000; 739:301–312.PubMedCrossRefGoogle Scholar
  42. 42.
    Vallee M, Mayo W, Darnaudery M, et al. Neurosteroids: deficient cognitive performance in aged rats depends on low pregnenolone sulfate levels in the hippocampus. Proc Natl Acad Sci USA 1997; 94:14865–14870.PubMedCrossRefGoogle Scholar
  43. 43.
    Wu FS, Gibbs TT, Farb DH. Pregnenolone sulfate: a positive allosteric modulator at the N-methyl-D-aspartate receptor. Mol Pharmacol 1991; 40:333–336.PubMedGoogle Scholar
  44. 44.
    Hojo Y, Nakajima K, Nakanishi H, et al.: Synthesis brain steroids and localization of P450s in the hippocampal neurons. In 20th IUBMB International Congress of Biochemistry and Molecular Biology, 2006:2PA-311.Google Scholar
  45. 45.
    Gu Q, Moss RL. 17 beta-Estradiol potentiates kainate-induced currents via activation of the cAMP cascade. J Neurosci 1996; 16:3620–3629.PubMedGoogle Scholar
  46. 46.
    Ito K, Skinkle KL, Hicks TP. Age-dependent, steroid-specific effects of oestrogen on long-term potentiation in rat hippocampal slices. J Physiol 1999; 515 (Pt 1):209–220.PubMedCrossRefGoogle Scholar
  47. 47.
    Mukai H, Tsurugizawa T, Ogiue-Ikeda M, et al. Local neurosteroid production in the hippocampus: influence on synaptic plasticity of memory. Neuroendocrinology 2006; 84:255–263.PubMedCrossRefGoogle Scholar
  48. 48.
    Teyler TJ, Vardaris RM, Lewis D, Rawitch AB. Gonadal steroids: effects on excitability of hippocampal pyramidal cells. Science 1980; 209:1017–1018.PubMedCrossRefGoogle Scholar
  49. 49.
    Mukai H, Tsurugizawa T, Murakami G, et al. Rapid modulation of long-term depression and spinogenesis via synaptic estrogen receptors in hippocampal principal neurons. J Neurochem 2007; 100:950–967.PubMedCrossRefGoogle Scholar
  50. 50.
    Kawato S. Endocrine disrupters as disrupters of brain function: a neurosteroid viewpoint. Environ Sci 2004; 11:1–14.PubMedGoogle Scholar
  51. 51.
    Migaud M, Charlesworth P, Dempster M, et al. Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein. Nature 1998; 396:433–439.PubMedCrossRefGoogle Scholar
  52. 52.
    Lee HK, Kameyama K, Huganir RL, Bear MF. NMDA induces long-term synaptic depression and dephosphorylation of the GluR1 subunit of AMPA receptors in hippocampus. Neuron 1998; 21:1151–1162.PubMedCrossRefGoogle Scholar
  53. 53.
    Harrington WR, Sheng S, Barnett DH, et al. Activities of estrogen receptor alpha- and beta-selective ligands at diverse estrogen responsive gene sites mediating transactivation or transrepression. Mol Cell Endocrinol 2003; 206:13–22.PubMedCrossRefGoogle Scholar
  54. 54.
    Yang SN, Tang YG, Zucker RS. Selective induction of LTP and LTD by postsynaptic [Ca2+]i elevation. J Neurophysiol 1999; 81:781–787.PubMedGoogle Scholar
  55. 55.
    Lisman J. A mechanism for the Hebb and the anti-Hebb processes underlying learning and memory. Proc Natl Acad Sci USA 1989; 86:9574–9578.PubMedCrossRefGoogle Scholar
  56. 56.
    Ogiue-Ikeda M, Tanabe N, Mukai H, et al. Rapid Modulation of Synaptic Plasticity by Estrogens as well as Endocrine Disrupters in Hippocampal Neurons. Brain Res Rev 2007 (in press).Google Scholar
  57. 57.
    Komatsuzaki Y, Murakami G, Tsurugizawa T, et al. Rapid spinogenesis of pyramidal neurons induced by activation of glucocorticoid receptors in adult male rat hippocampus. Biochem Biophys Res Commun 2005; 335:1002–1007.PubMedCrossRefGoogle Scholar
  58. 58.
    Murakami G, Tsurugizawa T, Hatanaka Y, et al. Comparison between basal and apical dendritic spines in estrogen-induced rapid spinogenesis of CA1 principal neurons in the adult hippocampus. Biochem Biophys Res Commun 2006; 351:553–558.PubMedCrossRefGoogle Scholar
  59. 59.
    Tsurugizawa T, Mukai H, Tanabe N, et al. Estrogen induces rapid decrease in dendritic thorns of CA3 pyramidal neurons in adult male rat hippocampus. Biochem Biophys Res Commun 2005; 337:1345–1352.PubMedCrossRefGoogle Scholar
  60. 60.
    Mukai H, Tsurugizawa, T, Murakami G, Kominami S, Ishii T, Ogiue-Ikeda M, Takata N, Tanabe N, Furukawa A, Hojo Y, Morrison JH, Janssen WGM, Rose JA, Chambon P, Kato S, Izumi S, Yamazaki T, Kimoto T, Kawato S. Rapid Modulation of Long-term Depression and Spinogenesis Depending on Synaptic Estrogen Receptors in Principal Neurons of Hippocampus. J. Neurochem. 2007; 100:950–967.PubMedCrossRefGoogle Scholar
  61. 61.
    Ishii H, Shibuya K, Ohta Y, et al. Enhancement of nitric oxide production by association of nitric oxide synthase with N-methyl-D-aspartate receptors via postsynaptic density 95 in genetically engineered Chinese hamster ovary cells: real-time fluorescence imaging using nitric oxide sensitive dye. J Neurochem 2006; 96:1531–1539.PubMedCrossRefGoogle Scholar
  62. 62.
    Monaghan DT, Holets VR, Toy DW, Cotman CW. Anatomical distributions of four pharmacologically distinct 3H-L-glutamate binding sites. Nature 1983; 306:176–179.PubMedCrossRefGoogle Scholar
  63. 63.
    Baude A, Nusser Z, Molnar E, et al. High-resolution immunogold localization of AMPA type glutamate receptor subunits at synaptic and non-synaptic sites in rat hippocampus. Neuroscience 1995; 69:1031–1055.PubMedCrossRefGoogle Scholar
  64. 64.
    Fritschy JM, Weinmann O, Wenzel A, Benke D. Synapse-specific localization of NMDA and GABA(A) receptor subunits revealed by antigen-retrieval immunohistochemistry. J Comp Neurol 1998; 390:194–210.PubMedCrossRefGoogle Scholar
  65. 65.
    Reid CA, Fabian-Fine R, Fine A. Postsynaptic calcium transients evoked by activation of individual hippocampal mossy fiber synapses. J Neurosci 2001; 21:2206–2214.PubMedGoogle Scholar
  66. 66.
    Reid CA. The role of dendritic spines: comparing the complex with the simple. Eur J Pharmacol 2002; 447:173–176.PubMedCrossRefGoogle Scholar
  67. 67.
    Leranth C, Petnehazy O, MacLusky NJ. Gonadal hormones affect spine synaptic density in the CA1 hippocampal subfield of male rats. J Neurosci 2003; 23:1588–1592.PubMedGoogle Scholar
  68. 68.
    Leranth C, Shanabrough M, Horvath TL. Hormonal regulation of hippocampal spine synapse density involves subcortical mediation. Neuroscience 2000; 101:349–356.PubMedCrossRefGoogle Scholar
  69. 69.
    MacLusky NJ, Luine VN, Hajszan T, 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; 146:287–293.PubMedCrossRefGoogle Scholar
  70. 70.
    Gould E, Woolley CS, Frankfurt M, McEwen BS. Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood. J Neurosci 1990; 10:1286–1291.PubMedGoogle Scholar
  71. 71.
    Woolley CS, Gould E, Frankfurt M, McEwen BS. Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons. J Neurosci 1990; 10:4035–4039.PubMedGoogle Scholar
  72. 72.
    Woolley CS, McEwen BS. Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat. J Neurosci 1992; 12:2549–2554.PubMedGoogle Scholar
  73. 73.
    Gu Q, Korach KS, Moss RL. Rapid action of 17beta-estradiol on kainate-induced currents in hippocampal neurons lacking intracellular estrogen receptors. Endocrinology 1999; 140:660–666.PubMedCrossRefGoogle Scholar
  74. 74.
    Couse JF, Curtis SW, Washburn TF, et al. Analysis of transcription and estrogen insensitivity in the female mouse after targeted disruption of the estrogen receptor gene. Mol Endocrinol 1995; 9:1441–1454.PubMedCrossRefGoogle Scholar
  75. 75.
    Kos M, Denger S, Reid G, et al. Down but not out? A novel protein isoform of the estrogen receptor alpha is expressed in the estrogen receptor alpha knockout mouse. J Mol Endocrinol 2002; 29:281–286.PubMedCrossRefGoogle Scholar
  76. 76.
    Pendaries C, Darblade B, Rochaix P, et al. The AF-1 activation-function of ERalpha may be dispensable to mediate the effect of estradiol on endothelial NO production in mice. Proc Natl Acad Sci USA 2002; 99:2205–2210.PubMedCrossRefGoogle Scholar
  77. 77.
    Dupont S, Krust A, Gansmuller A, et al. Effect of single and compound knockouts of estrogen receptors alpha (ERalpha) and beta (ERbeta) on mouse reproductive phenotypes. Development 2000; 127:4277–4291.PubMedGoogle Scholar
  78. 78.
    Pedram A, Razandi M, Levin ER. Nature of functional estrogen receptors at the plasma membrane. Mol Endocrinol 2006; 20:1996–2009.PubMedCrossRefGoogle Scholar
  79. 79.
    Razandi M, Pedram A, Greene GL, Levin ER. 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; 13:307–319.PubMedCrossRefGoogle Scholar
  80. 80.
    Milner TA, Ayoola K, Drake CT, et al. Ultrastructural localization of estrogen receptor beta immunoreactivity in the rat hippocampal formation. J Comp Neurol 2005; 491:81–95.PubMedCrossRefGoogle Scholar
  81. 81.
    Thomas P, Pang Y, Filardo EJ, Dong J. Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells. Endocrinology 2005; 146:624–632.PubMedCrossRefGoogle Scholar
  82. 82.
    Revankar CM, Cimino DF, Sklar LA, et al. A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science 2005; 307:1625–1630.PubMedCrossRefGoogle Scholar
  83. 83.
    Brailoiu E, Dun SL, Brailoiu GC, et al. Distribution and characterization of estrogen receptor G protein-coupled receptor 30 in the rat central nervous system. J Endocrinol 2007; 193:311–321.PubMedCrossRefGoogle Scholar
  84. 84.
    Papadopoulos V. Peripheral-type benzodiazepine/diazepam binding inhibitor receptor: biological role in steroidogenic cell function. Endocr Rev 1993; 14:222–240.PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, B.V 2008

Authors and Affiliations

  • Suguru Kawato
    • 1
  • Yasushi Hojo
    • 1
  • Hideo Mukai
    • 1
  • Gen Murakami
    • 1
  • Mari Ogiue-Ikeda
    • 1
  • Hirotaka Ishii
    • 1
  • Tetsuya Kimoto
    • 1
  1. 1.Department of Biophysics and Life SciencesUniversity of TokyoJapan

Personalised recommendations