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Neurochemical Research

, 33:1582 | Cite as

The PKC and ERK/MAPK Pathways Regulate Glucocorticoid Action on TRH Transcription

  • Antonieta Cote-Vélez
  • Leonor Pérez-Martínez
  • Jean-Louis Charli
  • Patricia Joseph-Bravo
Original Paper

Abstract

Biosynthesis of TRH, a neuropeptide involved in energy homeostasis, is modulated by glucocorticoids. TRH mRNA and peptide levels are increased upon incubation of hypothalamic cells with dexamethasone or with cAMP analogs but when combined, a mutual antagonism is observed. These effects are observed at the transcriptional level and on binding of glucocorticoid receptor (GR) or pCREB to the composite GRE (cGRE) and CRE-2 sites of TRH promoter. The present work studied the involvement of PKC and MAPK pathways on the effect of dexamethasone and on its interaction with cAMP signaling in hypothalamic cell cultures. PKC or MEK inhibition abolished dexamethasone-stimulatory effect on TRH mRNA levels, as well as its interference with the stimulatory effect of 8Br-cAMP. Binding of nuclear extracts from hypothalamic or neuroblastoma cells stimulated with dexamethasone or 8Br-cAMP to oligonucleotides containing the CRE or cGRE sites of TRH gene promoter was decreased if cells were preincubated with PKC or MEK inhibitors. Mutations on the AP-1 or the GRE half sites of cGRE showed that GR binds as an heterodimer on cGRE, and PKC or MEK inhibitors diminish binding at the AP-1 site. PKC and ERK signaling thus modulate GR activity and its interaction with CREB or AP-1 at the TRH gene promoter.

Keywords

TRH GR PKC ERK CREB AP-1 

Notes

Acknowledgements

We thank the technical support of F. Romero, M Villa, E. Martel, and E. Bustos, as well as S. González for animal care, and S. Ainsworth for bibliographic assistance. This work was supported by grants from CONACYT 43503 and DGAPA-UNAM 215507.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Antonieta Cote-Vélez
    • 1
  • Leonor Pérez-Martínez
    • 1
  • Jean-Louis Charli
    • 1
  • Patricia Joseph-Bravo
    • 1
  1. 1.Departamento de Genética y Fisiología Molecular, Instituto de BiotecnologíaUniversidad Nacional Autónoma de México (UNAM)CuernavacaMexico

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