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Transthyretin is up-regulated by sex hormones in mice liver

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Abstract

Misfolding and aggregation of mutated and wild-type transthyretin (TTR) can cause familial amyloid polyneuropathy (FAP) and senile systemic amyloidosis (SSA), respectively. In some populations, FAP onset seems to occur on average 2–11 years earlier in men than in women, and SSA appears to be a disease of elderly men. Most (95–100%) SSA patients described in the literature are men, suggesting that amyloid deposition in these patients may be sex hormone related. On the basis of gender-related differences in FAP onset, and on the almost exclusivity of SSA in elder men, we hypothesize that, sex hormones may increase TTR synthesis by the liver, and therefore, may contribute to amyloid deposition. In order to test this hypothesis, castrated female and male mice were implanted with alzet mini-osmotic pumps, delivering 17β-estradiol (E2) or 5α-dihydrotestosterone (DHT), or vehicle only, for 1 week. Sham operated animals were also included in the experiment. After hormonal stimulation, mice were euthanized under anaesthesia, and liver and sera were collected. The expression of TTR in liver, and the levels of TTR in sera in response to E2 and DHT were analysed by Real Time PCR and radioimmunoassay, respectively. Data analysis showed that, both hormones induced TTR transcription, which was concurrent with a consistent increase in the circulating levels of the protein. Taken together, all these data provide an indication that sex hormone stimulation may constitute a risk factor for SSA.

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Acknowledgements

I. Gonçalves and T. P. Quintela are recipients of fellowships from the Portuguese Foundation for Science and Technology-FCT, SRF/BPD/19337/2004 and SFRH/BD/21765/2005, respectively. C. H. Alves, and all the experimental work were supported by a FCT grant (POCI/SAU-NEU/55380/2004). We acknowledge Dr. J. E. B. Cavaco for carrying out orchydectomies.

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Authors and Affiliations

  1. Centre of Investigation in Health Sciences—CICS, University of Beira Interior, Av. Infante D. Henrique, 6200-506, Covilha, Portugal

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

  2. 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 & R. Abreu

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  1. I. Gonçalves
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Correspondence to C. R. A. Santos.

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Gonçalves, I., Alves, C.H., Quintela, T. et al. Transthyretin is up-regulated by sex hormones in mice liver. Mol Cell Biochem 317, 137–142 (2008). https://doi.org/10.1007/s11010-008-9841-2

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  • DOI: https://doi.org/10.1007/s11010-008-9841-2

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