Open AccessThe Immediate and Late Effects of Thyroid Hormone (Triiodothyronine) on Murine Coagulation Gene Transcription
Author(s) -
Salam Salloum-Asfar,
Anita Boelen,
Pieter H. Reitsma,
Bart J.M. van Vlijmen
Publication year - 2015
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0127469
Subject(s) - medicine , endocrinology , thyroid , triiodothyronine , hormone , euthyroid , coagulation , deiodinase , reverse triiodothyronine , biology
Thyroid dysfunction is associated with changes in coagulation. The aim of our study was to gain more insight into the role of thyroid hormone in coagulation control. C57Black/6J mice received a low-iodine diet and drinking water supplemented with perchlorate to suppress endogenous triiodothyronine (T 3 ) and thyroxine (T 4 ) production. Under these conditions, the impact of exogenous T 3 on plasma coagulation, and hepatic and vessel-wall-associated coagulation gene transcription was studied in a short- (4 hours) and long-term (14 days) setting. Comparing euthyroid conditions (normal mice), with hypothyroidism (conditions of a shortage of thyroid hormone) and those with replacement by incremental doses of T 3 , dosages of 0 and 0.5 μg T 3 /mouse/day were selected to study the impact of T 3 on coagulation gene transcription. Under these conditions, a single injection of T 3 injection increased strongly hepatic transcript levels of the well-characterized T 3 -responsive genes deiodinase type 1 ( Dio1 ) and Spot14 within 4 hours. This coincided with significantly reduced mRNA levels of Fgg , Serpinc1 , Proc , Proz , and Serpin10 , and the reduction of the latter three persisted upon daily treatment with T 3 for 14 days. Prolonged T 3 treatment induced a significant down-regulation in factor ( F ) 2 , F9 and F10 transcript levels, while F11 and F12 levels increased. Activity levels in plasma largely paralleled these mRNA changes. Thbd transcript levels in the lung (vessel-wall-associated coagulation) were significantly up-regulated after a single T 3 injection, and persisted upon prolonged T 3 exposure. Two-week T 3 administration also resulted in increased Vwf and Tfpi mRNA levels, whereas Tf levels decreased. These data showed that T 3 has specific effects on coagulation, with Fgg , Serpinc1 , Proc , Proz , Serpin10 and Thbd responding rapidly, making these likely direct thyroid hormone receptor targets. F2 , F9 , F10 , F11 , F12 , Vwf , Tf and Tfpi are late responding genes and probably indirectly modulated by T 3 .