title: Effects of silencing connexin43 on expression of pituitary tumor-transforming gene in prolactinomas.
abstract: OBJECTIVE
  Pituitary tumor transforming gene (PTTG) is thought to play an important role in prolactinomas, and its overexpression is influenced by estrogen action in the pituitary. Changes in estrogen levels in the rat anterior pituitary increase the number of gap junctions (GJs) increasing both Connexin43 (Cx43) expression and intercellular communication, contributing to pituitary tumor growth. The aim of this study was to investigate the effect of Cx43 on PTTG expression by silencing Cx43 expression using RNA interference (RNAi) in vivo.
  
  
  METHODS
  An experimental rat model of prolactinoma induced by estradiol (E2) treatment was used. Connexin43 RNAi was applied in vivo through the arachnoid space by injection of double-stranded RNA (dsRNA). Pituitary Cx43 immunostaining was examined using immunofluorescence and Cx43 and PTTG expression by both reverse-transcription-PCR (RT-PCR) and western blotting, respectively.
  
  
  RESULTS
  (1) Pituitaries treated with E2 were hypertrophic, but this was reduced by dsRNA treatment. (2) Pituitary Cx43 immunofluorescence increased following E2 treatment, but returned to normal levels following dsRNA treatment. (3) Estradiol induced Cx43 and PTTG expression, which decreased following dsRNA treatment.
  
  
  CONCLUSIONS
  Altered Cx43 expression modulates PTTG expression, which correlates with prolactinoma development. Thus, inhibiting gap junction intercellular communication (GJIC) as a means of weakening the pathologic role PTTG in prolactinomas may be of therapeutic interest.
authors.forename: Haitao
authors.initials: H
authors.lastname: Wang
authors.forename: Yaju
authors.initials: Y
authors.lastname: Zhang
authors.forename: Aiqin
authors.initials: A
authors.lastname: Zhou
authors.forename: Ran
authors.initials: R
authors.lastname: Zhang
authors.forename: Qinghai
authors.initials: Q
authors.lastname: Meng
mesh_terms: D000818:Animals; D018031:Connexin 43 / Q000096:biosynthesis*; D004958:Estradiol / Q000494:pharmacology; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D015175:Prolactinoma / Q000139:chemically induced / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D051381:Rats; D064249:Securin / Q000096:biosynthesis*
chemical_list: D018031:Connexin 43; D012330:RNA, Double-Stranded; D064249:Securin; D004958:Estradiol
keywords: Connexin43,; Estradiol,; Pituitary tumor transforming gene,; Prolactinoma; RNA interference,