title: Methimazole regulation of thyroglobulin biosynthesis and gene transcription in rat FRTL-5 thyroid cells.
abstract: Methimazole (MMI) increases thyroglobulin (Tg) mRNA levels in FRTL-5 rat thyroid cells. The increase reflects a transcriptional action of the antithyroid agent and is inhibited by cycloheximide, as is the transcriptional action of TSH. It takes several hours to be apparent, is maximal between 24-48 h, and is specific, in that thyroid peroxidase and beta-actin mRNA levels are not increased simultaneously. The increased mRNA levels are associated with increased recovery of immunoprecipitable Tg in the medium of cells exposed to [35S]methionine. The MMI effect appears to be independent of the action of TSH or its cAMP signal, since the MMI-induced increase in Tg mRNA levels is evident in cells treated with TSH or maintained in its absence and is associated not with increases in cAMP levels but, rather, under some circumstances with a decrease. The effect is evident under conditions in which the ability of insulin or insulin-like growth factor-I to increase Tg mRNA levels is already maximal. The MMI-induced increase is inhibited by concentrations of iodide associated with autoregulation of FRTL-5 rat thyroid cells, is inhibited but not mimicked by propylthiouracil, and is not altered by T3. The increase in Tg mRNA levels does not correlate with increased DNA synthesis as a function of MMI concentration either in cells treated with TSH or in those maintained in its absence. A concentration of MMI (5 mM) that increases Tg mRNA levels can also inhibit 8-bromo-cAMP- or phorbol ester-induced increases in [3H]thymidine incorporation into DNA.
authors.affiliation: Department of Medicine, Tokyo Women's Medical College, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Isozaki
authors.forename: T
authors.initials: T
authors.lastname: Tsushima
authors.forename: N
authors.initials: N
authors.lastname: Emoto
authors.forename: M
authors.initials: M
authors.lastname: Saji
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuchiya
authors.forename: H
authors.initials: H
authors.lastname: Demura
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.forename: K
authors.initials: K
authors.lastname: Shizume
authors.forename: S
authors.initials: S
authors.lastname: Kimura
authors.forename: L D
authors.initials: LD
authors.lastname: Kohn
mesh_terms: D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D006706:Homeostasis; D007454:Iodides / Q000494:pharmacology; D008713:Methimazole / Q000494:pharmacology*; D011441:Propylthiouracil / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013954:Thyroglobulin / Q000096:biosynthesis* / Q000235:genetics; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D013972:Thyrotropin / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D007454:Iodides; D012333:RNA, Messenger; D008713:Methimazole; D011441:Propylthiouracil; D013972:Thyrotropin; D004247:DNA; D013954:Thyroglobulin; D003513:Cycloheximide; D000242:Cyclic AMP