title: Stress and glucocorticoids increase transthyretin expression in rat choroid plexus via mineralocorticoid and glucocorticoid receptors.
abstract: Transthyretin (TTR) is a carrier for thyroid hormones and retinol binding protein. Several mutated forms of TTR cause familial amyloidotic polyneuropathy, an inheritable lethal disease. On the other hand, wild-type TTR has a protective role against Alzheimer's disease. Despite its overall importance in normal animal physiology and in disease, few studies have focused on its regulation. An in silico analysis of the rat TTR gene revealed a glucocorticoid responsive element in the 3' region of the first intron. Thus, we hypothesised that TTR could be regulated by glucocorticoid hormones and investigated the regulation of TTR expression in response to hydrocortisone in a rat choroid plexus cell line (RCP) and in primary cultures of choroid plexus epithelial cells (CPEC). In addition, the effect of psychosocial stress on TTR expression was analysed in rat liver, choroid plexus (CP) and cerebrospinal fluid (CSF). In RCP and CPEC cultures hydrocortisone upregulated TTR expression, an effect suppressed by glucocorticoid receptor and mineralocorticoid receptor antagonists. Moreover, induction of psychosocial stress increased TTR expression in liver, CP and CSF of animals subjected to acute and chronic stress conditions. Overall, we conclude that stress upregulates TTR expression in CP.
authors.affiliation: CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506, Covilhã, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Martinho
authors.forename: I
authors.initials: I
authors.lastname: Gonçalves
authors.forename: M
authors.initials: M
authors.lastname: Costa
authors.forename: C R
authors.initials: CR
authors.lastname: Santos
mesh_terms: D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D002831:Choroid Plexus / Q000166:cytology / Q000502:physiology*; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology; D006854:Hydrocortisone / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D011228:Prealbumin / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000235:genetics* / Q000378:metabolism; D013315:Stress, Psychological / Q000235:genetics* / Q000503:physiopathology
chemical_list: D005938:Glucocorticoids; D011228:Prealbumin; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D003345:Corticosterone; D006854:Hydrocortisone