title: Thyroid hormone activation in vascular smooth muscle cells is negatively regulated by glucocorticoid.
abstract: 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.
authors.affiliation: Department of Internal Medicine II, Kansai Medical University, Hirakata-City, Osaka, Japan. toyoda@takii.kmu.ac.jp
authors.forename: Nagaoki
authors.initials: N
authors.lastname: Toyoda
authors.forename: Saori
authors.initials: S
authors.lastname: Yasuzawa-Amano
authors.forename: Emiko
authors.initials: E
authors.lastname: Nomura
authors.forename: Azusa
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Kumiko
authors.initials: K
authors.lastname: Nishimura
authors.forename: Chizuko
authors.initials: C
authors.lastname: Ukita
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morimoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kosaki
authors.forename: Toshiji
authors.initials: T
authors.lastname: Iwasaka
authors.forename: John W
authors.initials: JW
authors.lastname: Harney
authors.forename: P Reed
authors.initials: PR
authors.lastname: Larsen
authors.forename: Mitsushige
authors.initials: M
authors.lastname: Nishikawa
mesh_terms: 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
chemical_list: D005938:Glucocorticoids; D012333:RNA, Messenger; D013963:Thyroid Hormones; D014284:Triiodothyronine; D007453:Iodide Peroxidase; D013974:Thyroxine; D003345:Corticosterone; D008797:Metyrapone