title: Regulation of thyroid peroxidase and thyroglobulin gene expression by thyrotropin in cultured human thyroid cells.
abstract: cDNAs for thyroid peroxidase (TPO) and thyroglobulin (Tg) have been cloned and sequenced. Using such cDNAs, we investigated the regulation of TPO and Tg gene expression by various agents in cultured human thyroid cells. Unstimulated human thyroid cells contained a major RNA species [3.2 kilobases (kb) in length] and several minor RNA species (less than 3.2 kb mRNA) of TPO, but no detectable Tg transcripts. However, TSH-stimulated thyroid cells contained four distinct TPO mRNA species (4.0, 3.2, 2.1, and 1.7 kb) and a single Tg mRNA species (8.5 kb). TSH stimulated the TPO and Tg mRNA levels in a dose- and time-dependent manner. The same results were obtained with 8-bromo-cAMP, a cAMP analog, but not with insulin or insulin-like growth factor I. Furthermore, inductions of these mRNAs by TSH and 8-bromo-cAMP were almost completely blocked by cycloheximide, a protein synthesis inhibitor. These results suggest that human thyroid cells contain four distinct TPO mRNAs and a single species of Tg mRNA, and the levels of all mRNAs are increased by TSH/cAMP stimulation. These increases are blocked by inhibiting protein synthesis, indicating that TSH stimulation of TPO and Tg mRNA levels may be mediated by newly synthesized protein(s).
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, Nagasaki University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nagayama
authors.forename: S
authors.initials: S
authors.lastname: Yamashita
authors.forename: H
authors.initials: H
authors.lastname: Hirayu
authors.forename: M
authors.initials: M
authors.lastname: Izumi
authors.forename: T
authors.initials: T
authors.lastname: Uga
authors.forename: N
authors.initials: N
authors.lastname: Ishikawa
authors.forename: K
authors.initials: K
authors.lastname: Ito
authors.forename: S
authors.initials: S
authors.lastname: Nagataki
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D001711:Biotransformation / Q000187:drug effects; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000032:analysis; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D013954:Thyroglobulin / Q000235:genetics* / Q000378:metabolism; D013961:Thyroid Gland / Q000201:enzymology*; D013972:Thyrotropin / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D012333:RNA, Messenger; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013972:Thyrotropin; D004247:DNA; D013954:Thyroglobulin; D003513:Cycloheximide; D007453:Iodide Peroxidase