A role for mitogen-activated protein kinase in mediating activation of the glycoprotein hormone α-subunit promoter by gonadotropin-releasing hormone

Mark S. Roberson, Anita Misra-Press, Megan E. Laurance, Philip J.S. Stork, Richard A. Maurer

Research output: Contribution to journalArticlepeer-review

195 Scopus citations

Abstract

Gonadotropin-releasing hormone (GnRH) interacts with a G protein-coupled receptor and increases the transcription of the glycoprotein hormone α- subunit gene. We have explored the possibility that mitogen-activated protein kinase (MAPK) plays a role in mediating GnRH effects on transcription. Activation of the MAPK cascade by an expression vector for a constitutively active form of the Raf-1 kinase led to stimulation of the α-subunit promoter in a concentration-dependent manner. GnRH treatment was found to increase the phosphorylation of tyrosine residues of MAPK and to increase MAPK activity, as determined by an immune complex kinase assay. A reporter gene assay using the MAPK-responsive, carboxy-terminal domain of the Elk1 transcription factor was also consistent with GnRH-induced activation of MAPK. Interference with the MAPK pathway by expression vectors for kinase-defective MAPKs or vectors encoding MAPK phosphatases reduced the transcription-stimulating effects of GnRH. The DNA sequences which are required for responses to GnRH include an Ets factor-binding site. An expression vector for a dominant negative form of Ets-2 was able to reduce GnRH effects on expression of the α-subunit gene. These findings provide evidence that GnRH treatment leads to activation of the MAPK cascade in gonadotropes and that activation of MAPK contributes to stimulation of the α-subunit promoter. It is likely that an Ets factor serves as a downstream transcriptional effector of MAPK in this system.

Original languageEnglish (US)
Pages (from-to)3531-3539
Number of pages9
JournalMolecular and cellular biology
Volume15
Issue number7
DOIs
StatePublished - Jul 1995

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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