title: Aberrant expression of thyroid hormone receptor beta isoform may cause inappropriate secretion of TSH in a TSH-secreting pituitary adenoma.
abstract: BACKGROUND
  Patients with TSH-secreting pituitary adenomas (TSHoma) show inappropriate secretion of TSH; serum TSH levels are not suppressed despite high serum free thyroid hormone levels. The mechanism of a defect in negative regulation of TSH in a TSHoma is still unclear.
  
  
  OBJECTIVE
  Recently, we cloned a novel thyroid hormone receptor β isoform (TRβ4) from a human pituitary library. To elucidate the clinical significance of TRβ4, we investigated the expression of this isoform in TSHoma.
  
  
  METHODS
  RT-PCR was performed to detect TRβ isoforms such as TRβ1, TRβ2, and TRβ4 using RNA obtained from surgically resected TSHoma. The effects of TRβ4 on the TSH gene expression were examined in the transient gene expression experiments.
  
  
  RESULTS
  Quantitative analysis using a real-time PCR revealed that relative expression of TRβ4 to TRβ1+2 was higher in three TSHoma than in a prolactinoma or a nonfunctioning pituitary adenoma. TRβ4 construct did not mediate T(3)-dependent gene regulation but inhibited the negative regulation of TSHα mediated by TRβ1 or TRβ2.
  
  
  CONCLUSIONS
  Aberrant expression of TRβ4 may partly contribute to the inappropriate secretion of TSH in a TSHoma.
authors.affiliation: Division of Endocrinology and Metabolism, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Mukaihata-cho 1-1, Fukakusa, Fushimi-ku, Kyoto 612-8555, Japan. ttagami@kyotolan.hosp.go.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tagami
authors.forename: Takeshi
authors.initials: T
authors.lastname: Usui
authors.forename: Akira
authors.initials: A
authors.lastname: Shimatsu
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Beniko
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Moriyama
authors.forename: Mitsuhide
authors.initials: M
authors.lastname: Naruse
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008875:Middle Aged; D010902:Pituitary Gland / Q000378:metabolism*; D010907:Pituitary Hormones / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D037042:Thyroid Hormone Receptors beta / Q000235:genetics / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism*
chemical_list: D010907:Pituitary Hormones; D020033:Protein Isoforms; D012333:RNA, Messenger; D037042:Thyroid Hormone Receptors beta; D013972:Thyrotropin