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17β-Estradiol Induces Transthyretin Expression in Murine Choroid Plexus via an Oestrogen Receptor Dependent Pathway

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Abstract

Oestrogen protects against AD by multiple mechanisms, including the enhancement of Aβ clearance. Transthyretin (TTR) is a homotetrameric protein mainly synthesized by the liver and choroid plexus (CP) of the brain that sequesters the amyloid beta (Aβ) peptide. In this study we examined the effects of 17β-estradiol (E2) on TTR protein and mRNA levels, in primary cultures of rat CP epithelial cells (CPEC) by Western blot and Real Time PCR, respectively. Moreover, the localization of oestrogen receptors alpha (ERα) and beta (ERβ) in response to E2 treatment was analysed by confocal microscopy in these cells. The expression of TTR, ERα and ERβ was also compared in the CP of castrated female mice treated with E2 to vehicle-treated animals by Real Time PCR. TTR concentration in the CSF of all these animals was measured by radioimmunoassay. E2 treatment induced TTR transcription and increased TTR protein content in CPEC. Pre-treatment with ICI 182,780 (ICI) abrogated E2-induced TTR expression suggesting that, TTR is up-regulated via an ER-dependent pathway. Confocal microscopy demonstrated extranuclear ERα and ERβ localization in untreated CPEC. Upon E2 treatment, translocation of ERα to the nucleus occurred, while ERβ remained in the cytosol. These data was concurrent with the up-regulation of TTR expression detected in the CP of castrated female mice subjected to E2 treatment. Our results highlight the importance of E2 on the regulation of TTR, which may participate in the oestrogen-induced decrease in Aβ levels and deposition described in the literature.

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Acknowledgements

T. Quintela and I. Gonçalves are recipients of PhD (SFRH/BD/21765/2005) and post-doctoral (SRF/BPD/19337/2004) fellowships, respectively, from the Portuguese Foundation for Science and Technology—FCT. C. H. Alves and the experimental work were supported by an FCT project to CRAS (POCI/SAU-NEU/55380/2004) and grant PTDC/SAU-OSM/64093/2006 to MJS.

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Authors and Affiliations

  1. Health Sciences Research Centre – CICS, University of Beira Interior, Av. Infante D. Henrique, 6200-506, Covilhã, Portugal

    T. Quintela, I. Gonçalves, G. Baltazar, C. H. Alves & C. R. A. Santos

  2. Department of Molecular Neurobiology, Institute of Molecular and Cellular Biology–IBMC, Porto and ICBAS, University of Porto, Rua do Campo Alegre, 823, 4150-180, Porto, Portugal

    M. J. Saraiva

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  1. T. Quintela
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  2. I. Gonçalves
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  6. C. R. A. Santos
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Correspondence to C. R. A. Santos.

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Quintela, T., Gonçalves, I., Baltazar, G. et al. 17β-Estradiol Induces Transthyretin Expression in Murine Choroid Plexus via an Oestrogen Receptor Dependent Pathway. Cell Mol Neurobiol 29, 475–483 (2009). https://doi.org/10.1007/s10571-008-9339-1

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