MISC

2008年4月

Involvement of bone morphogenetic protein-4 in GH regulation by octreotide and bromocriptine in rat pituitary GH3 cells

JOURNAL OF ENDOCRINOLOGY
  • Tomoko Miyoshi
  • ,
  • Fumio Otsuka
  • ,
  • Hiroyuki Otani
  • ,
  • Kenichi Inagaki
  • ,
  • Junko Goto
  • ,
  • Misuzu Yamashita
  • ,
  • Toshio Ogura
  • ,
  • Yasumasa Iwasaki
  • ,
  • Hirofumi Makino

197
1
開始ページ
159
終了ページ
169
記述言語
英語
掲載種別
DOI
10.1677/JOE-07-0549
出版者・発行元
SOC ENDOCRINOLOGY

Here we investigated roles of the pituitary bone morphogenetic protein (BMP) system in modulating GH production regulated by a somatostatin analog, octreotide (OCT) and a dopamine agonist, bromocriptine (BRC) in rat pituitary somatolactotrope tumor GH3 cells. The GH3 cells were found to express BMP ligands, including BMP-4 and BMP-6-1 BMP type-1 and type-2 receptors (except the type-1 receptor, activin receptor-like kinase (ALK)-6); and Smad signaling molecules. Forskolin stimulated GH production in accordance with cAMP synthesis. BRC, but not OCT, suppressed forskolin-induced cAMP synthesis by GH3 cells. Individual treatment with OCT and BRC reduced forskolin-induced GH secretion. A low concentration (0-1 mu M) of OCT in combination with BRC (1-100 mu M) exhibited additive effects on reducing GH and cAMP production induced by forskolin. However, a high concentration (10 mu M) of OCT in combination with BRC failed to suppress GH and cAMP production. BMP-4 specifically enhanced GH secretion and cAMP production induced by forskolin in GH3 cells. BRC, but not OCT, inhibited BMP4-induced activation of Smad1,5,8 phosphorylation and Id-1 transcription and decreased ALK-3 expression. Of note, in the presence of a high concentration of OCT, the BRC effects suppressing BMP-4-Smad1,5,8 signaling were significantly impaired. In the presence of BMP-4, a high concentration of OCT also attenuated the BRC effects suppressing forskolin-induced GH and cAMP production. Collectively, a high concentration of OCT interferes with BRC effects by reducing cAMP production and suppressing BMP-4 signaling in GH3 cells. These findings may explain the mechanism of resistance of GH reduction to a combination therapy with OCT and BRC for GH-producing pituitary adenomas.

リンク情報
DOI
https://doi.org/10.1677/JOE-07-0549
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000255187900016&DestApp=WOS_CPL
ID情報
  • DOI : 10.1677/JOE-07-0549
  • ISSN : 0022-0795
  • eISSN : 1479-6805
  • Web of Science ID : WOS:000255187900016

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