title: Propylthiouracil increases sodium/iodide symporter gene expression and iodide uptake in rat thyroid cells in the absence of TSH.
abstract: BACKGROUND
  Propylthiouracil (PTU) and methimazole (MMI) are drugs that are widely used to treat Graves' disease. Although both exert an antithyroid effect primarily by blocking thyroid peroxidase activity, their molecular structure and other actions are different. We hypothesized that PTU and MMI may have differential effects on thyroid-specific gene expression and function.
  
  
  METHODS
  The effects of PTU and MMI on thyroid-specific gene expression and function were examined in rat thyroid FRTL-5 cells using DNA microarray, reverse transcriptase (RT)-polymerase chain reaction (PCR), real-time PCR, Western blot, immunohistochemistry, and radioiodine uptake studies.
  
  
  RESULTS
  DNA microarray analysis showed a marked increase in sodium/iodide symporter (NIS) gene expression after PTU treatment, whereas MMI had no effect. RT-PCR and real-time PCR analysis revealed that PTU-induced NIS mRNA levels were comparable to those elicited by thyroid-stimulating hormone (TSH). PTU increased 5'-1880-bp and 5'-1052-bp activity of the rat NIS promoter. While PTU treatment also increased NIS protein levels, the size of the induced protein was smaller than that induced by TSH, and the protein localized predominantly in the cytoplasm rather than the plasma membrane. Accumulation of (125)I in FRTL-5 cells was increased by PTU stimulation, but this effect was weaker than that produced by TSH.
  
  
  CONCLUSIONS
  We found that PTU induces NIS expression and iodide uptake in rat thyroid FRTL-5 cells in the absence of TSH. Although PTU and MMI share similar antithyroid activity, their effects on other thyroid functions appear to be quite different, which could affect their therapeutic effectiveness.
authors.affiliation: Laboratory of Molecular Diagnostics, Department of Mycobacteriology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Sue
authors.forename: Takeshi
authors.initials: T
authors.lastname: Akama
authors.forename: Akira
authors.initials: A
authors.lastname: Kawashima
authors.forename: Hannah
authors.initials: H
authors.lastname: Nakamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hara
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tanigawa
authors.forename: Huhehasi
authors.initials: H
authors.lastname: Wu
authors.forename: Aya
authors.initials: A
authors.lastname: Yoshihara
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ishido
authors.forename: Naoki
authors.initials: N
authors.lastname: Hiroi
authors.forename: Gen
authors.initials: G
authors.lastname: Yoshino
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Kohn
authors.forename: Norihisa
authors.initials: N
authors.lastname: Ishii
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D006111:Graves Disease / Q000378:metabolism; D007454:Iodides / Q000378:metabolism; D008713:Methimazole / Q000494:pharmacology; D011441:Propylthiouracil / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D027981:Symporters / Q000096:biosynthesis* / Q000235:genetics; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology*; D000099209:Sodium-Iodide Symporters
chemical_list: D007454:Iodides; D008713:Methimazole; D011441:Propylthiouracil; D012333:RNA, Messenger; D027981:Symporters; D013972:Thyrotropin; D000099209:Sodium-Iodide Symporters