Activation of the GDNF-inducible transcription factor (GIF) gene promoter by glucocorticoid and progesterone

Sang Hyeon Lee, Min Kyung Jang, Ok Soo Kim, Ok Hee Lee, Nam Young Kim, Ki Hwan Yoo, Dong Geun Lee, Young Hwa Shong, M. Maral Mouradian

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Steroid hormones, especially glucocorticoids, exert physiologic effects on dopaminergic neurotransmission and have been implicated in several dopamine-mediated neuropsychiatric conditions. D2 dopamine receptor gene expression is regulated by the zinc finger-type nuclear protein GDNF-inducible transcription factor (GIF). In this study, we sought to investigate if steroids could regulate transcription of the GIF gene itself. Transient co-transfection of the D2 expressing neuroblastoma cell line NB41A3 with GIF promoter-luciferase constructs along with expression vectors for steroid hormone receptors showed that activation of glucocorticoid receptors but not estrogen receptors up-regulates transcription from the GIF promoter 5.0-fold. Progesterone receptors, which share the same consensus DNA recognition sequence as glucocorticoid receptors, also activated the GIF promoter. Serial 5′-deletion mutants of the GIF gene upstream region localized the glucocorticoid-responsive segment between nucleotides -128 and -66 relative to the transcription start site. This region contains a putative glucocorticoid-responsive element/progesterone-responsive element (GRE/PRE). Additionally, this fragment of the GIF gene 5′-upstream region activated the heterologous herpes simplex virus thymidine kinase (TK) promoter, which is known to be glucocorticoid and progesterone responsive. Furthermore, glucocorticoid receptor activation up-regulated endogenous GIF gene mRNA expression in NB41A3 cells. These observations demonstrate a molecular basis for glucocorticoid and progesterone-induced up-regulation of GIF gene transcription and provide a mechanism for the modulation of dopamine-mediated behaviors by these hormones.

Original languageEnglish (US)
Pages (from-to)30-35
Number of pages6
JournalJournal of Steroid Biochemistry and Molecular Biology
Issue number1-2
StatePublished - May 2009

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology


  • GIF promoter
  • Glucocorticoid
  • Luciferase
  • Progesterone


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