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Östrogene im Gehirn

Estrogens in the brain

  • Leitthema
  • Published:
Gynäkologische Endokrinologie Aims and scope

Zusammenfassung

Östrogene regulieren im Gehirn nicht nur die Geschlechtsdifferenzierung, sie beeinflussen auch das Sexualverhalten, die neuronale Aktivität und wirken neuroprotektiv. Im neuronalen Gewebe lassen sich von nukleären Östrogenrezeptoren (ERα und ERβ) vermittelte, genomische Östrogeneffekte von schnellen, nichtgenomischen Effekten unterscheiden. Bei den nichtgenomischen Effekten handelt es sich überwiegend um Einflüsse auf die Signaltransduktion von Neuronen, deren Vermittlung vermutlich von membranständigen ERs abhängt. Das Östrogen synthetisierende Enzym Aromatase kommt in diversen Hirnregionen vor, und die Expression des Aromatasegens wird gewebespezifisch mithilfe eines hirnspezifischen Promotors gesteuert. Die Aktivität der Aromatase wird in Neuronen kurzfristig durch Phosphorylierung reguliert und kann u. a. durch neuronale Aktivität beeinflusst werden. Experimentelle Studien zeigen, dass Östrogene bei neurodegenerativen Erkrankungen protektiv wirken können, was hier am Beispiel des zerebralen Insults dargestellt wird. Da diese Befunde im Widerspruch zu einigen klinischen Studien stehen, ist weitere Forschung notwendig, um Östrogene bei neuronalen Erkrankungen therapeutisch einsetzen zu können.

Abstract

In the brain, estrogens have a variety of functions: they regulate sexual differentiation, sexual behavior, and neuronal activity and demonstrate neuroprotective actions. In neuronal tissue, genomic estrogen effects can be distinguished from rapid, non-genomic effects through cellular signal transduction. The genomic effects are mediated by nuclear estrogen receptors (ERα and ERβ), whereas the non-genomic effects are very likely to depend on membranous ERs. Estrogens are synthesized by aromatase, an enzyme that is expressed in various brain regions. A brain-specific promoter regulates the tissue-specific expression of the aromatase gene. The aromatase activity can rapidly be regulated by phosphorylation and is influenced by neuronal activity. Preclinical studies demonstrate the protective effects of estrogens with respect to neurodegenerative diseases, such as stroke. More research will be necessary in order to close the gap between these preclinical results and data from clinical trials and to develop estrogen therapies for neuronal diseases.

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Literatur

  1. Bulun SE, Takayama K, Suzuki T et al (2004) Organization of the human aromatase P450 (CYP19) gene. Semin Reprod Med 22:5–9

    Article  CAS  PubMed  Google Scholar 

  2. Carswell HVO, Macrae IM, Farr TD (2010) Complexities of oestrogen in stroke. Clin Sci (Lond) 118:375–389

    Google Scholar 

  3. Charlier TD, Cornil CA, Ball GF et al (2010) Diversity of mechanisms involved in aromatase regulation and estrogen action in the brain. Biochim Biophys Acta 1800:1094–1105

    CAS  PubMed  Google Scholar 

  4. Dahlman-Wright K, Cavailles V, Fuqua SA et al (2006) International Union of Pharmacology. LXIV. Estrogen Receptors. Pharmacol Rev 58:773–781

    Article  CAS  PubMed  Google Scholar 

  5. Garcia-Segura LM (2008) Aromatase in the brain: not just for reproduction anymore. J Neuroendocrinol 20:705–712

    Article  CAS  PubMed  Google Scholar 

  6. Garcia-Segura LM, Balthazart J (2009) Steroids and neuroprotection: new advances. Front Neuroendocrinol 30:V–IX

    Article  PubMed  Google Scholar 

  7. Gillies GE, McArthur S (2010) Estrogen actions in the brain and the basis for differential action in men and women: a case for sex-specific medicines. Pharmacol Rev 62:155–198

    Article  CAS  PubMed  Google Scholar 

  8. Honda S, Harada N, Takagi Y (1994) Novel exon-1 of the aromatase gene-specific for aromatase transcripts in human brain. Biochem Biophys Res Commun 198:1153–1160

    Article  CAS  PubMed  Google Scholar 

  9. Kelly MJ, Ronnekleiv OK (2009) Control of CNS neuronal excitability by estrogens via membrane-initiated signaling. Mol Cell Endocrinol 308:17–25

    Article  CAS  PubMed  Google Scholar 

  10. Mermelstein PG (2009) Membrane-localised oestrogen receptor alpha and beta influence neuronal activity through activation of metabotropic glutamate receptors. J Neuroendocrinol 21:257–262

    Article  CAS  PubMed  Google Scholar 

  11. Micevych P, Dominguez R (2009) Membrane estradiol signaling in the brain. Front Neuroendocrinol 30:315–327

    Article  CAS  PubMed  Google Scholar 

  12. Morris JA, Jordan CL, Breedlove SM (2004) Sexual differentiation of the vertebrate nervous system. Nat Neurosci 7:1034–1039

    Article  CAS  PubMed  Google Scholar 

  13. Naftolin F, Ryan KJ, Petro Z (1971) Aromatization of androstenedione by the diencephalon. J Clin Endocrinol Metab 33:368–370

    Article  CAS  PubMed  Google Scholar 

  14. Ortmann O (2009) Hormontherapie in der Peri- und Postmenopause (HT). In: DGGG (Hrsg) Interdisziplinäre S 3-Leitlinie. http://www.dggg.de/fileadmin/public_docs/Leitlinien/2-1-4-ht-lang-hp1.pdf (zitiert 10.11.2010)

  15. Parker KL, Schimmer BP (1997) Steroidogenic ractor 1: a key determinant of endocrine development and function. Endocr Rev 18:361–377

    Article  CAS  PubMed  Google Scholar 

  16. Rissman EF (2008) Roles of oestrogen receptors alpha and beta in behavioural neuroendocrinology: beyond yin/yang. J Neuroendocrinol 20:873–879

    Article  CAS  PubMed  Google Scholar 

  17. Roselli CE, Liu MY, Hurn PD (2009) Brain aromatization: classic roles and new perspectives. Semin Reprod Med 27:207–217

    Article  CAS  PubMed  Google Scholar 

  18. Rossouw JE, Anderson GL, Prentice RL et al (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women – principal results from the Women’s Health Initiative randomized controlled trial. JAMA 288:321–333

    Article  CAS  PubMed  Google Scholar 

  19. Suzuki S, Brown CM, Wise PM (2009) Neuroprotective effects of estrogens following ischemic stroke. Front Neuroendocrinol 30:201–211

    Article  CAS  PubMed  Google Scholar 

  20. Toran-Allerand CD (2005) Estrogen and the brain – beyond ER-alpha, ER-beta, and 17 beta-estradiol. In: Singh M, Simpkins JW (Hrsg) Future of hormone therapy: What basic science and clinical studies teach us. Academy of Sciences, New York, S 136–144

  21. Wehrenberg U, Prange-Kiel J, Rune GM (2001) Steroidogenic factor-1 expression in marmoset and rat hippocampus: co-localization with StAR and aromatase. J Neurochem 76:1879–1886

    Article  CAS  PubMed  Google Scholar 

  22. Yilmaz MB, Wolfe A, Cheng Y-H et al (2009) Aromatase promoter I.f is regulated by estrogen receptor alpha (ESR1) in mouse hypothalamic neuronal cell lines. Biol Reprod 81:956–965

    Article  CAS  PubMed  Google Scholar 

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  1. Southwestern Medical Center at Dallas, Department of Cell Biology, University of Texas, 5323 Harry Hines Blvd, 75390-9039, Dallas, TX, USA

    J. Prange-Kiel

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Correspondence to J. Prange-Kiel.

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Prange-Kiel, J. Östrogene im Gehirn. Gynäkologische Endokrinologie 9, 8–13 (2011). https://doi.org/10.1007/s10304-010-0391-9

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  • DOI: https://doi.org/10.1007/s10304-010-0391-9

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