Progesterone enhances transthyretin expression in the rat choroid plexus in vitro and in vivo via progesterone receptor.
Depletion of ovarian hormones 17β-estradiol (E2) and progesterone (P) after menopause may contribute to the decline in cognitive performance and increases the risk of Alzheimer's disease (AD) in women, striking the importance of understanding the regulation of pivotal proteins involved in AD pathogenesis by ovarian hormones. Transthyretin (TTR) is now recognized as one of such proteins due to its ability to sequester and degrade amyloid β (Aβ) into less harmful peptides and preventing their aggregation. We have previously demonstrated that E2 enhances TTR expression. In this study, we investigate the effects of P on TTR expression in primary cultures of rat choroid plexus epithelial cells and in adult ovariectomized female rats. The results obtained demonstrate that, in vitro and in vivo, TTR is up-regulated by P. In addition, the mechanism underlying the response of TTR to P was investigated, and we provide evidence that this response is achieved through a progesterone receptor-mediated mechanism. Our results reinforce the importance of ovarian hormones on the regulation of TTR, which may reflect on the processing of Aβ peptides and consequently on AD onset and progression.
Health Sciences Research Centre-CICS, University of Beira Interior, Av. Infante D. Henrique, Covilhã, Portugal.
Telma
T
Quintela
Isabel
I
Gonçalves
Ana
A
Martinho
Celso Henrique
CH
Alves
Maria João
MJ
Saraiva
Pedro
P
Rocha
Cecília Reis Alves
CR
Santos
D000818:Animals; D002478:Cells, Cultured; D002831:Choroid Plexus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D010052:Ovariectomy; D011228:Prealbumin / Q000235:genetics / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011980:Receptors, Progesterone / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D011228:Prealbumin; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D011374:Progesterone