Thyroid hormone activation in vascular smooth muscle cells is negatively regulated by glucocorticoid.
BACKGROUND
Type 2 iodothyronine deiodinase (D2) catalyzes the production of triiodothyronine from thyroxine. D2 is present in rat aorta media, and there is a circadian variation in the D2 expression. In rat aorta media, the D2 activity exhibited the maximal value at 1200 hour and low value between 1800 and 2400 hour. To understand the mechanisms that induce the circadian variation in the D2 expression, we examined the effects of glucocorticoid on the D2 activity and mRNA in rat aorta media and cultured vascular smooth muscle cells (VSMCs).


METHODS
The effects of intrinsic and extrinsic glucocorticoid on the D2 activity and mRNA in rat aorta media were studied using metyrapone, a corticosterone synthesis inhibitor, and dexamethasone (DEX). Further, the effects of DEX on D2 expression were studied using the cultured rat VSMCs.


RESULTS
The trough values of D2 activity and mRNA at 2100 hour were increased by the treatment with metyrapone. On the other hand, the peak values of D2 activity and mRNA were decreased by the treatment with DEX. D2 activity and mRNA in cultured rat VSMCs were increased by the addition of 10(-3) M dibutyryl cyclic adenosine monophosphate [(Bu)(2)cAMP]. The increments were reduced by coincubation with 10(-6) M DEX.


CONCLUSIONS
These results suggest that glucocorticoids might directly suppress the D2 expression in rat VSMCs induced by a cAMP-dependent mechanism.
Toyoda
Nagaoki
N
Department of Internal Medicine II, Kansai Medical University, Hirakata-City, Osaka, Japan. toyoda@takii.kmu.ac.jp
Yasuzawa-Amano
Saori
S
Nomura
Emiko
E
Yamauchi
Azusa
A
Nishimura
Kumiko
K
Ukita
Chizuko
C
Morimoto
Satoshi
S
Kosaki
Atsushi
A
Iwasaka
Toshiji
T
Harney
John W
JW
Larsen
P Reed
PR
Nishikawa
Mitsushige
M
D000818:Animals; D002478:Cells, Cultured; D002940:Circadian Rhythm; D003345:Corticosterone / Q000097:blood; D015971:Gene Expression Regulation, Enzymologic; D005938:Glucocorticoids / Q000494:pharmacology* / Q000502:physiology; D007453:Iodide Peroxidase / Q000378:metabolism; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000378:metabolism*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D005938:Glucocorticoids; D012333:RNA, Messenger; D013963:Thyroid Hormones; D014284:Triiodothyronine; D007453:Iodide Peroxidase; D013974:Thyroxine; D003345:Corticosterone; D008797:Metyrapone