Orexin A modulates prolactin production by regulating BMP-4 activity in rat pituitary lactotorope cells

Satoshi Fujisawa, Motoshi Komatsubara, Kanako Ogura-Ochi, Naoko Tsukamoto-Yamauchi, Kishio Toma, Kenichi Inagaki, Jun Wada, Fumio Otsuka

Research output: Contribution to journalArticle

Abstract

The impact of orexins on anterior pituitary function has yet to be clarified. We studied the effects of orexin A and its interaction with the bone morphogenetic protein (BMP) system on the regulatory role of prolactin synthesis using rat lactotrope GH3 cells expressing BMP-4. Orexin type 1 receptor (OX1R), but not type 2 receptor (OX2R), was predominantly expressed in GH3 cells. Orexin A suppressed forskolin-induced, but not basal, prolactin mRNA expression without reducing cAMP levels. Of note, orexin A suppressed BMP-4-induced prolactin mRNA and cAMP synthesis. Impairment of the effects of orexin by chemical inhibitors suggested involvement of the P38 pathway in the OX1R activity that suppresses BMP-4-induced PRL expression. Given that inhibition of BMP-receptor signaling reduced prolactin mRNA levels, endogenous BMP action is likely to be linked to the activation of prolactin synthesis by GH3 cells. Orexin A was revealed to suppress Smad1/5/9 phosphorylation and Id-1 transcription induced by BMP-4, which was restored in the presence of orexin-receptor antagonists, suggesting that the inhibitory effect of orexin A occurred via OX1R. Orexin A also reduced ALK-3 expression but increased inhibitory Smad6/7 expression, while BMP-4 treatment downregulated OX1R expression. These results indicated that orexin A plays an inhibitory role in prolactin production through suppression of endogenous BMP activity in GH3 cells, suggesting that a new functional role of the interaction between orexin and BMP-4 is modulation of prolactin levels in lactotrope cells.

Original languageEnglish
Pages (from-to)35-40
Number of pages6
JournalPeptides
Volume113
DOIs
Publication statusPublished - Mar 1 2019

    Fingerprint

Keywords

  • Bone morphogenetic protein
  • Lactotrope
  • Orexin
  • Pituitary
  • Prolactin

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

Cite this