Evidence from studies with N-ethyl-maleimide and 12-O-tetradecanoylphorbol-13-acetate that AP-1 and CREB are involved in the glucocorticoid activation of TRH gene expression in hypothalamic cultures

Brain Res. 1999 Sep 11;841(1-2):189-92. doi: 10.1016/s0006-8993(99)01789-8.

Abstract

To determine whether c-fos/c-jun (AP-1) and CREB mediate glucocorticoid stimulated TRH gene regulation, we investigated the effect of N-ethyl-maleimide (NEM), an alkylating agent, and 12-O-tetradecanoylphorbol-13-acetate (TPA) on this process. NEM decreased while TPA increased TRH levels in rat hypothalamic culture, changes similar to their effects on CREB and Fos/Jun proteins in the AtT20 cell line. This suggests that glucocorticoid stimulation of TRH gene expression may be regulated by the AP-1 complex and CREB pathway.

MeSH terms

  • Animals
  • Cells, Cultured
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Dexamethasone / pharmacology*
  • Dimerization
  • Ethylmaleimide / pharmacology*
  • Fetus
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Genes, fos
  • Genes, jun
  • Hypothalamus / cytology
  • Hypothalamus / metabolism*
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Rats
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Thyrotropin-Releasing Hormone / genetics*
  • Transcription Factor AP-1 / metabolism*

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Transcription Factor AP-1
  • Thyrotropin-Releasing Hormone
  • Dexamethasone
  • Tetradecanoylphorbol Acetate
  • Ethylmaleimide