Estradiol regulation of lipocalin-type prostaglandin D synthase promoter activity: evidence for direct and indirect mechanisms

Neurosci Lett. 2010 Apr 19;474(1):17-21. doi: 10.1016/j.neulet.2010.02.064. Epub 2010 Mar 1.


In the CNS, lipocalin-type prostaglandin D synthase (L-PGDS) is predominantly a non-neuronal enzyme responsible for the production of PGD(2), an endogenous sleep promoting substance. We have previously demonstrated that estradiol differentially regulates L-PGDS transcript levels in the rodent brain. In hypothalamic nuclei, estradiol increases L-PGDS transcript expression, whereas in the ventrolateral preoptic area L-PGDS gene expression is reduced after estradiol treatment. In the present study, we have used an immortalized glioma cell line transfected with a L-PGDS reporter construct and estrogen receptor (ER) alpha and ERbeta expression plasmids to further elucidate the mechanisms underlying estradiol regulation of L-PGDS gene expression. We found that physiologically relevant concentrations of estradiol evoked an inverted U response in cells expressing ERalpha. The most effective concentration of estradiol (10(-11)M) increased the promoter activity 3-fold over baseline. Expression of ERbeta did not increase activity over control and when ERbeta was co-expressed with ERalpha there was a significant attenuation of the promoter activity. While ERalpha significantly increased L-PGDS promoter activity, our previous in vivo studies demonstrate a greater magnitude of change in L-PGDS gene expression in the presences of estradiol. This led us to ask whether estradiol is signaling via a paracrine factor released by the neighboring neurons. Conditioned media from estradiol treated neurons applied to the glioma cell line resulted in a significant 7-fold increase in L-PGDS promoter activity supporting the possibility that neuronal-glial interactions are involved in estradiol regulation of L-PGDS.

Publication types

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

MeSH terms

  • Biological Factors / metabolism
  • Cell Line, Tumor
  • Culture Media, Conditioned
  • Estradiol / pharmacology*
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / physiology
  • Estrogen Receptor beta / genetics
  • Estrogen Receptor beta / physiology
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Intramolecular Oxidoreductases / biosynthesis*
  • Intramolecular Oxidoreductases / genetics
  • Lipocalins / biosynthesis*
  • Lipocalins / genetics
  • Neuroglia / metabolism
  • Neurons / metabolism
  • Paracrine Communication
  • Transcription, Genetic


  • Biological Factors
  • Culture Media, Conditioned
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Lipocalins
  • Estradiol
  • Intramolecular Oxidoreductases
  • prostaglandin R2 D-isomerase