Transthyretin is up-regulated by androgens in mice liver and choroid plexus

Cecilia RA Santos; Alves C Henrique; Maria Joao Saraiva; Raquel Abreu; Graça Baltazar; Silvia Socorro; Telma P Quintela; Isabel MT Gonçalves

P276

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Endocrine Abstracts (2007) 14 P276

ECE2007 Poster Presentations (1) (659 abstracts)

Transthyretin is up-regulated by androgens in mice liver and choroid plexus

Cecilia RA Santos ¹ , C Henrique Alves ¹ , Maria Joao Saraiva ² , Raquel Abreu ² , Graça Baltazar ¹ , Silvia Socorro ¹ , Telma P Quintela ¹ & Isabel MT Gonçalves ¹

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¹Centre of Investigation in Health Sciences-CICS, Universidade da Beira Interior, Covilhã, Portugal; ²Molecular Neurobiology, Instituto de Biologia Molecular e Celular-IBMC and ICBAS, Universidade do Porto, Porto, Portugal.

Transthyretin (TTR) is well documented as a carrier for thyroid hormones. It also binds retinol binding protein preventing its filtration trough the kidneys and therefore is involved in delivering retinol to target cells. Moreover, TTR sequesters amyloid-beta impairing its deposition in nervous tissues and possibly contributing to its removal. Despite its importance in mammalian physiology, there are few studies regarding the regulation of TTR synthesis. In silico analysis of the 5′ flanking region of the TTR gene allowed the identification of androgen responsive elements suggesting that androgens may regulate TTR expression in tissues where TTR and androgen receptor (AR) are co-expressed. This could assume particular relevance in the liver and choroid plexus (CP), which are the major sites of TTR synthesis. To test this hypothesis female and male mice were either ovariectomized (n=13) or orchidectomized (n=12). Five weeks after surgery, these animals were either implanted with an alzet mini-osmotic pump delivering 419 ug/Kg/day of 5α-dyhidrotestosterone (DHT) or vehicle only, in the subscapular region. Sham operated animals (5 females and 5 males), not implanted, were also included in the experiment. After one week of hormonal stimulation, mice were euthanized and CP, livers, cerebrospinal fluid (CSF) and sera were collected and frozen at −80 °C. The levels of TTR in the CSF and sera were measured by RIA and the expression of TTR in the liver and choroid plexus was analysed by Real-Time PCR. A 3-fold increase of TTR levels in the sera and CSF of females, and a slight but significant increase of TTR levels in the sera of males were observed. As AR is expressed in liver and CP, it is likely that the observed TTR response to DHT is mediated by AR.