17β-estradiol-induced regulation of the novel 5-HT1A-related transcription factors NUDR and Freud-1 in SH SY5Y cells

Cell Mol Neurobiol. 2012 May;32(4):517-21. doi: 10.1007/s10571-012-9809-3. Epub 2012 Feb 11.

Abstract

Nuclear deformed epidermal autoregulatory factor-1 (NUDR/Deaf-1) and five prime repressor element under dual repression (Freud-1) are novel transcriptional regulators of the 5-HT(1A) receptor, a receptor that has been implicated in the pathophysiology of various psychiatric illnesses. The antidepressant effect of 17β-Estradiol (17βE(2)) is purported to involve the downregulation of this receptor. We investigated the possible role of NUDR and Freud-1 in 17βE(2)-induced downregulation of the 5-HT(1A) receptor in the neuroblastoma cell line SH SY5Y. Cells were treated with 10 nM of 17βE(2) for 3 or 48 h, followed by a 24-h withdrawal period. Proteins were isolated and analyzed by western blotting. 17βE(2) treatment increased NUDR immunoreactivity while Freud-1 and the 5-HT(1A) receptor showed significant decreases. Upon withdrawal of 17βE(2), protein expression returned to control levels, except for NUDR, which remained significantly elevated in the 3-h treatment. Taken together, these data support a non-genomic downregulation of 5-HT(1A) receptor protein by 17βE(2), which does not involve NUDR and Freud-1. Rather, changes in both transcription factors seem to be compensatory/homeostatic responses to changes in 5-HT(1A) receptor induced by 17βE(2). These observations further highlight the importance of NUDR and Freud-1 in regulating 5-HT(1A) receptor expression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers / metabolism
  • Cell Line, Tumor
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Depressive Disorder / genetics
  • Depressive Disorder / metabolism*
  • Depressive Disorder / pathology
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Estradiol / physiology*
  • Humans
  • Neuroblastoma
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Receptor, Serotonin, 5-HT1A / genetics*

Substances

  • Biomarkers
  • CC2D1A protein, human
  • DEAF1 protein, human
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Receptor, Serotonin, 5-HT1A
  • Estradiol