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Estrogens and the Brain

Implications for the Treatment of Postmenopausal Women

  • Chapter
Selective Estrogen Receptor Modulators

Part of the book series: Contemporary Endocrinology ((COE))

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Abstract

The actions of estrogens in the brain go well beyond the regulation of reproduction and include effects upon mood, cognitive function, motor coordination, pain, and protection of the brain from certain forms of damage. Multiple receptor mechanisms are believed to be involved, including at least two types of intracellular estrogen receptors (ERα and ERβ) and nonnuclear, nongenomic actions of estrogens that may involve a form of the intracellular receptors or other as-yet-unidentified receptor types. Selective estrogen response modulators (SERMs) interact with these many mechanisms of estrogen action in different ways, acting primarily as agonists or antagonists or having no effects in some cases. For this reason, it is difficult to imagine that SERMs or any other substitute for estradiol itself will mimic all of the brain effects of 17-β estradiol itself. Rather, the challenge is to develop therapeutic strategies that emphasize particular beneficial effects of estrogens on the brain, such as neuroprotection, while minimizing the possible antagonism of other estrogen actions that are beneficial.

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References

  1. Pfaff DW. Estrogens and Brain Function. New York: Springer-Verlag 1980.

    Book  Google Scholar 

  2. McEwen BS, Alves SH. Estrogen Actions in the Central Nervous System. Endocrine Rev 1999; 20: 279–307.

    Article  CAS  Google Scholar 

  3. Jensen E, Jacobson H. Basic guides to the mechanism of estrogen action. Rec Prog Horm Res 1962; 18: 387–408.

    CAS  Google Scholar 

  4. Smith EP, Boyd J, Frank RG, et al. Estrogen Resistance Caused By A Mutation In The Estrogen-Receptor Gene In A Man. N Engl J Med 1994; 331: 1056–1061.

    Article  PubMed  CAS  Google Scholar 

  5. Kuiper GGJM, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson J-A. Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 1996; 93: 5925–5930.

    Article  PubMed  CAS  Google Scholar 

  6. Tremblay GB, Tremblay A, Copeland NG, Gilbert DJ, Jenkins NA, Labrie F, Giguere V. Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor P. Mol Endocrinol 1997; 11: 353–365.

    Article  PubMed  CAS  Google Scholar 

  7. Pettersson K, Grandien K, Kuiper GGJM, Gustafsson J-A. Mouse estrogen receptor (3 forms estrogen response element-binding heterodimers with estrogen receptor a. Mol Endocrinol 1997; 11: 1486 1496.

    Google Scholar 

  8. Chu S, Fuller PJ. Identification of a splice variant of the rat estrogen receptor beta gene. Mol Cell Endocrinol 1997; 132: 195–199.

    Article  PubMed  CAS  Google Scholar 

  9. Maruyama K, Endoh H, Sasaki-Iwaoka H, et al. A novel isoform of rat estrogen receptor beta with 18 amino acid insertion in the ligand binding domain as a putative dominant negative regular of estrogen action. Biochem Biophys Res Commun 1998; 246: 142–147.

    Article  PubMed  CAS  Google Scholar 

  10. Korach KS. Insights from the Study of Animals Lacking Functional Estrogen Receptor. Science 1994; 266: 1524–1527.

    Article  PubMed  CAS  Google Scholar 

  11. Smith EP, Boyd J, Frank GR, et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med 1994; 331: 1056–1061.

    Article  PubMed  CAS  Google Scholar 

  12. Krege JH, Hodgin JB, Couse JF, et al. Generation and reproductive phenotypes of mice lacking estrogen receptor P. Proc Natl Acad Sci USA 1998; 95: 15677–15682.

    Article  PubMed  CAS  Google Scholar 

  13. Ogawa S, Chan J, Chester AE, Gustafsson J-A, Korach KS, Pfaff DW. Survival of reproductive behaviors in estrogen receptor, gene-deficient (ERKO) male and female mice. Proc Natl Acad Sci USA 1999; 96: 12887–12892.

    Article  PubMed  CAS  Google Scholar 

  14. Kuiper GGJM, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S, Gustafsson J-A. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors a and p. Endocrinology 1997; 138: 863–870.

    Article  PubMed  CAS  Google Scholar 

  15. Pfaff DW, Keiner M. Atlas of estradiol-concentrating cells in the central nervous system of the female rat. J Comp Neurol 1973; 151: 121–158.

    Article  PubMed  CAS  Google Scholar 

  16. Stumpf WE, Sar M. Steroid hormone target sites in the brain: The differential distribution of estrogen, progestin, androgen and glucocorticosteoroid. J Steroid Biochem 1976; 7: 1163–1170.

    Article  PubMed  CAS  Google Scholar 

  17. Shughrue PJ, Scrimo PJ, Merchenthaler I. Estrogen binding and estrogen receptor characterization (ERa and ER(3), in the cholinergic neurons of the rat basal forebrain. Neuroscience 2000; 96: 41–49.

    Article  PubMed  CAS  Google Scholar 

  18. Kuiper GGJM, Shughrue PJ, Merchenthaler I, Gustafsson J-A. The estrogen receptor [3 subtype: A novel mediator of estrogen action in neuroendocrine systems. Front Neuroendocrinol 1998; 19: 253–286.

    Article  PubMed  CAS  Google Scholar 

  19. Shughrue PJ, Lane MV, Merchenthaler I. Comparative distribution of estrogen receptor-a and -(3 mRNA in the rat central nervous system. J Comp Neurol 1997; 388: 507–525.

    Article  PubMed  CAS  Google Scholar 

  20. Paech K, Webb P, Kuiper GGJM, et al. Differential ligand activation of estrogen receptors ERa and ER(3 at API sites. Science 1997; 277: 1508–1510.

    Article  PubMed  CAS  Google Scholar 

  21. Hrabovszky E, Kallo I, Hajszan T, Shughrue PJ, Merchenthaler I, Liposits Z. Expression of estrogen receptor-(3 messenger ribonucleic acid in oxytocin and vasopressin neurons of the rat supraoptic and paraventricular nuclei. Endocrinology 1998; 139: 2600–2604.

    Article  PubMed  CAS  Google Scholar 

  22. Roy E, MacLusky N, McEwen BS. Antiestrogen inhibits the induction of progestin receptors by estradiol in the hypothalamus, pituitary and uterus. Endocrinology 1979; 104: 1333–1336.

    Article  PubMed  CAS  Google Scholar 

  23. Meisel R, Dohanich G, McEwen BS, Pfaff DW. Antagonism of sexual behavior in female rats by ventromedial hypothalamic implants of antiestrogen. Neuroencrinol 1987; 45: 201–207.

    Article  CAS  Google Scholar 

  24. Luine V, McEwen BS. Effects of an estrogen antagonist on enzyme activities and 3H estradiol nuclear binding in uterus, pituitary and brain. Endocrinology 1977; 100: 903–910.

    Article  PubMed  CAS  Google Scholar 

  25. Winsberg ME, Sachs N, Tate DL, Adalsteinsson E, Spielman D, Ketter TA. Decreased dorsolateral prefrontal N-acetyl aspartate in bipolar disorder. Biol Psychiat 2000; 47: 475–481.

    Article  PubMed  CAS  Google Scholar 

  26. Goy R, McEwen BS. Sexual Differentiation of the Brain. Cambridge, MA: MIT Press 1980; p. 223.

    Google Scholar 

  27. Naftolin F. Brain aromatization of androgens. J Reprod Med 1994; 39: 257–261.

    PubMed  CAS  Google Scholar 

  28. Schneider LS, Farlow MR, Henderson VW, Pogoda JM. Effects of estrogen replacement therapy on response to tacrine in patients with Alzheimer’s disease. Neurology 1996; 46: 1580–1584.

    Article  PubMed  CAS  Google Scholar 

  29. Bethea CL, Pecins-Thompson M, Schutzer WE, Gundlah CLZN. Ovarian steroids and serotonin neural function. Mol Neurobiol 1999; 18: 87–123.

    Article  Google Scholar 

  30. Schmidt Pi, Nieman LK, Danaceau MA, Adams LF, Rubinow DR. Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. N Engl J Med 1998; 338: 209–216.

    Article  Google Scholar 

  31. Schneider LS, Small GW, Hamilton SH, Bystritsky A, Nemeroff CB. Meyers BS. Estrogen replacement and the response to fluoxetine in a multicenter geriatric depression trial. Am J Geriatr Psych 1997; 5: 97–106.

    CAS  Google Scholar 

  32. Mermelstein PG, Becker JB, Surmeier DJ. Estradiol reduces calcium currents in rat neostriatal neurons via a membrane receptor. J Neurosci 1996; 16: 595–604.

    PubMed  CAS  Google Scholar 

  33. Tseng JY, Kolb PE, Raskind MA, Miller MA. Estrogen regulates galanin but not tyrosine hydroxylase gene expression in the rat locus coeruleus. Mol Brain Res 1997; 50: 100–106.

    Article  PubMed  CAS  Google Scholar 

  34. Weiland NG. Glutamic Acid Decarboxylase Messenger Ribonucleic Acid Is Regulated by Estradiol and Progesterone in the Hippocampus. Endocrinology 1992; 131: 2697–2702.

    Article  PubMed  CAS  Google Scholar 

  35. Weiland NG, Orikasa C, Hayashi S, McEwen BS. Localization of Estrogen Receptors in the Hippo-campus of Male and Female Rats. Abstract, Soc Neurosci 1996; 22: 618.

    Google Scholar 

  36. Murphy DD, Cole NB, Greenberger V, Segal M. Estradiol increases dendritic spine density by reducing GABA neurotransmission in hippocampal neurons. J Neurosci 1998; 18: 2550–2559.

    PubMed  CAS  Google Scholar 

  37. Murphy DD, Cole NB, Segal M. Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons. Proc Natl Acad Sci USA 1998; 95: 11412–11417.

    Article  PubMed  CAS  Google Scholar 

  38. Amandusson A, Hermanson, O, Blomqvist A. Colocalization of oestrogen receptor immunoreactivity and preproenkephalin mRNA expression to neurons in the superficial laminae of the spinal and medullary dorsal horn of rats. Eur J Neuro 1996; 8: 2440–2445.

    Article  CAS  Google Scholar 

  39. Mogil JS, Sternberg WF, Kest B, Marek P, Liebeskind JC. Sex differences in the antagonism of swim stress-induced analgesia: effects of gonadectomy and estrogen replacement. Pain 1993; 53: 17–25.

    Article  PubMed  CAS  Google Scholar 

  40. Mogil JS, Richards SP, O’Toole LA, et al. Identification of a sex-specific quantitative trait locus mediating nonopioid stress-induced analgesia in female mice. J Neurosci 1997; 17: 7995–8002.

    PubMed  CAS  Google Scholar 

  41. Sternberg WF, Mogil JS, Kent B, et al. Neonatal testosterone exposure influences neurochemistry of swim stress-induced analgesia in adult mice. Pain 1996; 63: 321–326.

    Article  Google Scholar 

  42. Langub MC, Watson RE. Estrogen receptor-immunoreactive glia, endothelia, and ependyma in guinea pig preoptic area and median eminence: electron microscopy. Endocrinology 1992; 130: 364–372.

    Article  PubMed  CAS  Google Scholar 

  43. Shi J, Simpkins JW. 1713-estradiol modulation of glucose transporter 1 expression in blood-brain barrier. Am J Physiol 1997; 272: E1016 - E1022.

    PubMed  CAS  Google Scholar 

  44. McEwen BS. Ovarian steroids have diverse effects on brain structure and function. In: The Modern Management of the Menopause. ( Berg G, Hammar M, eds), pp. 269–278. New York: Parthenon 1994.

    Google Scholar 

  45. Rubinow DR. The premenstrual syndrome: New views. JAMA 1992; 268: 1908–1912.

    Article  PubMed  CAS  Google Scholar 

  46. Klaiber EL, Brovermann DM, Vogel W, Peterson LG, Snyder MB. Individual differences in changes in mood and platelet monoamine oxidase (MAO) activity during hormonal replacement therapy in menopausal women. Psychoneuronendocrinology 1996; 21: 575–592.

    Article  CAS  Google Scholar 

  47. Kendall DA, Stancel GM, Enna SJ. The influence of sex hormones on antidepressant-induced alterations in neurotransmitter receptor binding. J Neurosci 1982; 2: 354–360.

    PubMed  CAS  Google Scholar 

  48. Terasawa E, Timiras P. Electrical activity during the estrous cycle of the rat: cyclic changes in limbic structures. Endocrinology 1968; 83: 207–216.

    Article  PubMed  CAS  Google Scholar 

  49. Gee K. Steroid modulation of the GABA/Benzodiazepine Receptor-Linked Chloride Ionophore. Mol Neurobiol 1988; 2: 291–317.

    Article  PubMed  CAS  Google Scholar 

  50. Bonuccelli U, Melis GB, Paoletti AM, Fioretti P, Muni L, Muratoria A. Unbalanced progesterone and estradiol secretion in catamenial epilepsy. Epilepsy Res 1989; 3: 100–106.

    Article  PubMed  CAS  Google Scholar 

  51. Herzog AG. Reproductive endocrine considerations and hormonal therapy for women with epilepsy. Epilepsy 1991; 62: S27 - S33.

    Article  Google Scholar 

  52. Kimura D. Sex differences in the brain. Scientific American 1992; 267: 119–125.

    Article  Google Scholar 

  53. Gu Q, Korach KS, Moss RL. Rapid action of 1713-estradiol on kainate-induced currents in hippocampal neurons lacking intracellular estrogen receptors. Endocrinology 1999; 140: 660–666.

    Article  PubMed  CAS  Google Scholar 

  54. Woolley C, McEwen BS. Estradiol regulates hippocampal dendritic spine density via an N-methylD-aspartate receptor dependent mechanism. J Neurosci 1994; 14: 7680–7687.

    PubMed  CAS  Google Scholar 

  55. Woolley CS, Weiland NG, McEwen BS, Schwartzkroin PA. Estradiol increases the sensitivity of hippocampal CA1 pyramidal cells to NMDA receptor-mediated synaptic input: correlation with dendritic spine density. J Neurosci 1997; 17: 1848–1859.

    PubMed  CAS  Google Scholar 

  56. Woolley C, McEwen BS. 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.

    Article  PubMed  CAS  Google Scholar 

  57. Sherwin BB, Tulandi T. “Add-Back” Estrogen Reverses Cognitive Deficits Induced by a Gonadotropin-Releasing Hormone Agonist in Women with Leiomyomata Uteri. J Clin Endocrinol Metab 1996; 81: 2545–2549.

    Article  PubMed  CAS  Google Scholar 

  58. Garcia-Segura LM, Chowen JA. Endocrine glia-roles of glial-cells in the brain actions of steroid and thyroid-hormones and in the regulation of hormone secretion. Front Neuroendocrinol 1996; 17: 180–211.

    Article  PubMed  CAS  Google Scholar 

  59. Woolley C, Gould E, Frankfurt M, McEwen BS. Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons. J Neurosci 1990; 10: 4035–4039.

    PubMed  CAS  Google Scholar 

  60. Wise PM, Dubai DB, Wilson ME, Rau S, Liu Y. Estrogens: a trophic and protective factor in the adult brain. Front Neuroendocrinol 2001; 22: 33–66.

    Article  PubMed  CAS  Google Scholar 

  61. Hall ED, Braughler JM. Free radicals in CNS injury. 81–105. New York: Raven 1993.

    Google Scholar 

  62. Scogin FR. Assessment of depression in older adults: a guide for practitioners. pp 61–80. Washington: American Psychological Association 1994.

    Google Scholar 

  63. Koenig HG, Blazer DG. Minor depression in late life. Am J Geriatr Psych 1996; 4: 514 - S21.

    Google Scholar 

  64. Carlson LE, Sherwin BB, Chertkow HM. Relationship between mood and estradiol (E2) levels of Alzheimer’s disease (AD) patients. J Gerontol 2000; 55B: P47 - P53.

    Article  CAS  Google Scholar 

  65. Sherwin BB. Estrogenic Effects on Memory in Women. Ann NY Acad Sci 1994; 743: 213–231.

    Article  PubMed  CAS  Google Scholar 

  66. Green RA. Cerebral blood flow. Fertility and Sterility 2000; 143–73.

    Google Scholar 

  67. Bishop J, Simpkins JW. Estradiol enhances brain glucose uptake in ovariectomized rats. Brain Res Bull 1995; 36: 315–320.

    Article  PubMed  CAS  Google Scholar 

  68. Nappi RE, Sinforiani E, Mauri M, Bond G, Polatti F, Nappi G. Memory functioning at menopause: impact of age in ovariectomized women. Gyn Ob Invest 1999; 47: 29–36.

    Article  CAS  Google Scholar 

  69. Matthews KA, Cauley J, Yaffe K, Zmuda JM. Estrogen replacement therapy and cognitive decline in older community women. J Am Geriat Soc 1999; 47: 518–523.

    PubMed  CAS  Google Scholar 

  70. Steffens DC, Notelovitz M, Plassman BL, et al. Enhanced cognitive performance with estrogen use in non-demented community-dwelling older women. J Am Geriat Soc 1999; 47: 1171–1175.

    PubMed  CAS  Google Scholar 

  71. Jacobs D, Tang MX, Stern Y, et al. Cognitive function in nondemented older women who took estrogen after menopause. Neurol 1998; 50: 368–373.

    Article  CAS  Google Scholar 

  72. Fedor-Freyberg P. The influence of oestrogens on the well being and mental performance in climateric and postmenopausal women. Acta Obstet Gynecol Scand 1977; 64: 3–69.

    Google Scholar 

  73. Kampen DL, Sherwin BB. Estrogen use and verbal memory in healthy postmenopausal women. Obstet Gynecol 1994; 83: 979–983.

    Article  PubMed  CAS  Google Scholar 

  74. Robinson D, Friedman L, Marcus R, Tinklenberg J, Yesavage J. Estrogen replacement therapy and memory in older women. J Am Geriatr Soc 1994; 42: 919–922.

    PubMed  CAS  Google Scholar 

  75. Kimura D. Estrogen replacement therapy may protect against intellectual decline in postmenopausal women. Horm Behav 1995; 29: 312–321.

    Article  PubMed  CAS  Google Scholar 

  76. Barrett-Connor E, Kritz-Silverstein D. Estrogen replacement therapy and cognitive function in older women. JAMA 1993; 269: 2637–2641.

    Article  PubMed  CAS  Google Scholar 

  77. Rauramo L, Lagerspetz K, Engblom P, Punnonen R. The effect of castration and peroral estrogen therapy on some psychological functions. Acta Obstet Gynecol Scand 1976; 51: 3–15.

    CAS  Google Scholar 

  78. Bari MD, Williamson J, Pahor M. Missing data in epidemiological studies of age-associated cognitive decline. J Am Geriat Soc 1999; 47: 1380–1381.

    PubMed  Google Scholar 

  79. Bauer DC, Browner WS, Cauley JA, Orwoll ES, Scott JC, Black DM et al. Factors associated with appendicular bone mass in older women. The Study of Osteoporotic Fractures Research Group. Ann Int Med 1993; 118: 657–665.

    PubMed  CAS  Google Scholar 

  80. Heiss CJ, Sanborn CF, Nichols DL, Bonnick SL, Alford BB. Associations of body fat distribution, circulating sex hormones, and bone density in postmenopausal women. J Clin Endocrinol Metab 1995; 80: 1591–1596.

    Article  PubMed  CAS  Google Scholar 

  81. Yaffe K, Browner W, Cauley J, Launer LJ, Harris TB. Association between bone mineral density and cognitive decline in older women. J Am Geriat Soc 1999; 47: 1176–1182.

    PubMed  CAS  Google Scholar 

  82. Ferrini RL, Barrett-Connor EL. Sex hormones and age: a cross-sectional study of testosterone and estradiol and their bioavailable fractions in community-dwelling men. Am J Epidemiol 1998; 147: 750–754.

    Article  PubMed  CAS  Google Scholar 

  83. Tang MX, Jacobs D, Stern Y, et al. Effect of oestrogen during menopause on risk and age at onset of Alzheimer’s disease. Lancet 1996; 348: 429–432.

    Article  PubMed  CAS  Google Scholar 

  84. Mathews K, Cauley J, Yaffe K, Zmuda JM. Estrogen replacement therapy and cognitive decline in older women. J Am Geriat Soc 1999; 47: 518–523.

    Google Scholar 

  85. Mulnard RA, Cotman CW, Kawas C, et al. Estrogen replacement therapy for treatment of mild to moderate Alzheimer’s disease: a 1-year randomized controlled trial. JAMA 2000; 283: 1054–1055.

    Article  Google Scholar 

  86. Cordes EH, Saunders AM, Stittmatter WJ. Apolipoprotein E, survival in Alzheimer’s disease patients, and competing risks of death and Alzheimer’s disease. Neurol 1996; 45: 1323–1328.

    Google Scholar 

  87. Johnson JK, McCleary R, Oshita MH, Cotman CW. Initiation and propagation stages of B-amyloid are associated with distinctive apolipoprotein E, age, and gender profiles. Brain Res 1998; 798: 18–24.

    Article  PubMed  CAS  Google Scholar 

  88. Poirier J. Apolipoprotein E in animal models of CNS injury and in Alzheimer’s disease. Trend Neurosci 1994; 17: 525–530.

    CAS  Google Scholar 

  89. Snipes GJ, McGuire CB, Norden JJ, Freeman JA. Nerve injury stimulates the secretion of apolipoprotein E by nonneuronal cell. Proc Natl Acad Sci USA 1986; 83: 1130–1134.

    Article  CAS  Google Scholar 

  90. Boyles JK, Zoellner CD, Anderson JL, et al. A role for apolipoprotein E, apolipoprotein A-I, and low density lipoprotein receptors in cholesterol transport during regeneration and remyelination of the rat sciatic nerve. J Clin Invest 1989; 83: 1015–1031.

    Article  PubMed  CAS  Google Scholar 

  91. Holtzman DM, Pitas RE, Kilbridge J, et al. Low density lipoprotein receptor-related protein mediates apolipoprotein E-dependent neurite outgrowth in a central nervous system-derived neuronal cell line. Proc Natl Acad Sci USA 1995; 92: 9480–9484.

    Article  PubMed  CAS  Google Scholar 

  92. Holtzman DM, Bales KR, Wu S, et al. Expression of human apolipoprotein E reduces amyloid-beta deposition in a mouse model of Alzheimer’s disease. J Clin Invest 1999; 103: R15 - R21.

    CAS  Google Scholar 

  93. Stone DJ, Rozovsky I, Morgan TE, Anderson CP, Hajian H, Finch CE. Astrocytes and microglia respond to estrogen with increased ApoE mRNA in vivo and in vitro. Exp Neurol 1997; 143: 313–318.

    Article  PubMed  CAS  Google Scholar 

  94. Stone DJ, Rozovsky I, Morgan TE, Anderson CP, Finch CE. Increased synaptic sprouting in response to estrogen via an apolipoprotein E-dependent mechanism• implications for Alzheimer’s disease. J Neurosci 1998; 3180–3185.

    Google Scholar 

  95. McEwen BS. Stress and hippocampal plasticity. Ann Rev Neurosci 1999; 22: 105–122.

    Article  PubMed  CAS  Google Scholar 

  96. Uno H, Ross T, Else J, Suleman M, Sapolsksy R. Hippocampal damage associated with prolonged and fatal stress in primates. J Neurosci 1989; 9: 1709–1711.

    Google Scholar 

  97. Seeman TE, Singer BH, Rowe JW, Horwitz RI, McEwen BS. Price of adaptation-allostatic load and its health consequences: MacArthur studies of successful aging. Arch Intern Med 1997; 157: 2259 2268.

    Google Scholar 

  98. Van Cauter E, Leproult R, Kupfer DJ. Effects of Gender and Age on the Levels and Circadian Rhythmicity of Plasma Cortisol. J Clin Endocrinol Metab 1996; 81: 2468–2473.

    Article  PubMed  Google Scholar 

  99. Seeman TE, Singer B, Charpentier P. Gender Differences In Patterns of HPA Axis Response To Challenge: MacArthur Studies Of Successful Aging. Psychoneuroendocrinology 1995; 20: 711–725.

    CAS  Google Scholar 

  100. Komesaroff PA, Esler MD, Sudhir K. Estrogen supplementation attenuates glucocorticoid and catecholamine responses to mental stress in perimenopausal women. J Clin Endocrinol Metab 1999; 84: 606–610.

    Article  PubMed  CAS  Google Scholar 

  101. Lindheim SR, Legro RS, Bernstein L, et al. Behavioral stress responses in premenopausal and postmenopausal women and the effects of estrogen. Am J Obstet Gyn 1992; 167: 1831–1836.

    CAS  Google Scholar 

  102. Devanand DP, Sano M, Tang M-X, et al. Depressed mood and the incidence of Alzheimer’s disease in the elderly living in the community. Arch Gen Psychiat 1996; 53: 175–182.

    Article  PubMed  CAS  Google Scholar 

  103. Weiner MF, Edland SD, Luszczynska H. Prevalence and incidence of major depression in Alzheimer’ s disease. Am J Psych 1994; 15: 1006–1009.

    Google Scholar 

  104. Nevitt MC, Hudes ES. Risk factors for injurious falls: a prospective study. J Gerontol 1991; 46:M164-M 170.

    Google Scholar 

  105. Birge SJ, Morrow-Howell N, Proctor EK. Hip fracture. Clin Geriatr Med 1994; 10: 589–609.

    CAS  Google Scholar 

  106. Ball LJ, Bisher GB, Birge SJ. A simple test of central processing speed: an extension of the Short Blessed Test. J Am Geriat Soc 1999; 47: 1359–1363.

    PubMed  CAS  Google Scholar 

  107. Robinovitch SN, Hayes WC, McMahon TA. Prediction of femoral impact forces in falls on the hip. J Biomech Eng 1991; 113: 366–374.

    Article  PubMed  CAS  Google Scholar 

  108. Melton LJ, Kan SH, Wahner HW, Rigg K. Lifetime fracture risk: an approach to hip fracture risk assessment based on bone mineral density and age. J Clin Epidemiol 1988; 41: 985–994.

    Article  PubMed  Google Scholar 

  109. Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures. JAMA 1998; 280: 2077–2082.

    Article  PubMed  CAS  Google Scholar 

  110. Ettinger B, Black DM, Mitlak BH, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene. Results from a 3-year randomized clinical trial. JAMA 1999; 282: 637–689.

    Article  PubMed  CAS  Google Scholar 

  111. Naessen T, Lindmark B, Larsen HC. Better postural balance in elderly women receiving estrogens. Am J Obstet Gynecol 1997; 177: 412–416.

    Article  PubMed  CAS  Google Scholar 

  112. Honkanen R, Komulainon M, Honkanen K. Hormone replacement therapy prevents falls in early postmenopausal women. European Congress on Osteoporosis. 1998;286:Abstract.

    Google Scholar 

  113. Aronson MK, Ooi WL, Morgenstern H, et al. Women, myocardial infarction, and dementia in the very old. Neurol 1990; 40: 1102–1106.

    Article  CAS  Google Scholar 

  114. Berlinger WG, Potter JE. Low body mass index in demented outpatients. J Am Geriat Soc 1991; 39: 973–978.

    PubMed  CAS  Google Scholar 

  115. Black DM, Cummings SR, Karpf DB, et al. Randomized trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 1996; 348: 1535–1541.

    Article  PubMed  CAS  Google Scholar 

  116. Cathcart CK, Jones SE, Pumroy CS, Peters GW, Knox SMCJH. Clinical recognition and management of depression in node negative breast cancer patients treated with tamoxifen. Breast Can Res Treat 1993; 27: 277–281.

    Article  CAS  Google Scholar 

  117. Perez CA, Graham ML, Taylor ME, et al. Management of locally advanced carcinoma of the breast. Noninflammatory Cancer 1994; 74: 453–465.

    CAS  Google Scholar 

  118. Paganini-Hill A, Henderson VW. Estrogen replacement therapy and risk of Alzheimer’s disease. Arch Int Med 1996; 156: 2213–2217.

    Article  CAS  Google Scholar 

  119. Schmidt R, Fazekas F, Reinhart B, et al. Estrogen replacement therapy in older women: a neuropsychological and brain MRI study. J Am Geriat Soc 1996; 44: 1307–1313.

    PubMed  CAS  Google Scholar 

  120. Watson CS, Pappas TC, Gametchu B. The other estrogen receptor in the plasma membrane: Implications for the actions of environmental estrogens. Environmental Health Perspectives 1995; 103: 41–50.

    PubMed  CAS  Google Scholar 

  121. Razandi M, Pedram A, Greene GL, Levin ER. Cell membrane and nuclear estrogen receptors (ERs) originate from a single transcript: Studies of Elba and ERf3 expressed in Chinese hamster ovary cells. Mol Endocrinol 1999; 13: 307–319.

    Article  PubMed  CAS  Google Scholar 

  122. Boyle M, MacLusky N, Naftolin F, Kaczmarek L. Hormonal regulation of K± channel messenger RNA in rat myometrium during oestrus cycle and in pregnancy. Nature 1987; 330: 373–375.

    Article  PubMed  CAS  Google Scholar 

  123. Joees M, Karst H. Effects of Estradiol and Progesterone on Voltage-Gated calcium and Potassium Conductances in Rat CA1 Hippocampal Neurons. J Neurosci 1995; 15: 4289–4297.

    Google Scholar 

  124. Zhou Y, Watters JJ, Dorsa DM. Estrogen rapidly induces the phosphorylation of the cAMP response element binding protein in rat brain. Endocrinology 1997; 137: 2163–2166.

    Article  Google Scholar 

  125. Gu G, Rojo AA, Zee MC, Yu J, Simerly RD. Hormonal Regulation of CREB Phosphorylation in the Anteroventral Periventricular Nucleus. J Neurosci 1996; 16: 3035–3044.

    PubMed  CAS  Google Scholar 

  126. Singh M, Setalo GJr, Guan X, Warren M, Toran-Allerand CD. Estrogen-induced activation of mitogen-activated protein kinase in cerebral cortical explants: Convergence of estrogen and neurotrophin signaling pathways. J Neurosci 1999; 19: 1179–1188.

    PubMed  CAS  Google Scholar 

  127. Morley P, Whitfield JF, Vanderhyden BC, Tsang BK, Schwartz J-L. A new nongenomic estrogen action: The rapid release of intracellular calcium. Endocrinology 1992; 131: 1305–1312.

    Article  PubMed  CAS  Google Scholar 

  128. Green PS, Gridley KE, Simpkins JW. Estradiol protects against 13-amyloid (25–35)-induced toxicity in SK-N-SH human neuroblastoma cells. Neurosci Lett 1996; 218: 165–168.

    Article  PubMed  CAS  Google Scholar 

  129. Singer CA, Rogers KL, Stickland TM, Dorsa DM. Estrogen protects primary cortical neurons from glutamate toxicity. Neurosci Lett 1996; 212: 13–16.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Bruce S. McEwen PhD
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  2. Phyllis M. Wise PhD
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  3. Stanley Birge MD
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Editors and Affiliations

  1. Division of Endocrinology, Diabetes, and Metabolism, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, PA, USA

    Andrea Manni MD  & Michael F. Verderame PhD  & 

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© 2002 Humana Press, Totowa, NJ

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McEwen, B.S., Wise, P.M., Birge, S. (2002). Estrogens and the Brain. In: Manni, A., Verderame, M.F. (eds) Selective Estrogen Receptor Modulators. Contemporary Endocrinology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-157-2_7

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  • DOI: https://doi.org/10.1007/978-1-59259-157-2_7

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4684-9665-9

  • Online ISBN: 978-1-59259-157-2

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