Intracellular signaling involved in estrogen regulation of serotonin reuptake

Nina Koldzic-Zivanovic, Patricia K. Seitz, Cheryl Watson, Kathryn A. Cunningham, Mary L. Thomas

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


17β-Estradiol (E 2) regulates neuronal activity via genomic and rapid, non-genomic mechanisms. The rat serotonergic neuronal cell line (RN46A) was used to investigate the rapid effects of E 2 on serotonin (5-HT) reuptake and on potential intracellular signaling pathways. RN46A cells express the serotonin transporter (SERT) and estrogen receptor (ER)β, but not ERα. Fifteen minute E 2 treatment (10 -9 M) decreased 5-HT uptake. Intracellular cAMP levels were not increased by 15 min E 2 treatment; however, E 2 caused an increase in intracellular Ca 2+ levels, with a maximum response within the first minute. The response was E 2 specific, since other steroids (17α-estradiol, testosterone, and progesterone) had no effect. The ER antagonist ICI 182,780 blocked the rapid E 2 effects on intracellular Ca 2+ levels as did the selective ER modulator tamoxifen. In summary, changes in intracellular Ca 2+ levels caused by E 2 and mediated through ERβ may be responsible for observed rapid effects of E 2 on SERT activity.

Original languageEnglish (US)
Pages (from-to)33-42
Number of pages10
JournalMolecular and Cellular Endocrinology
Issue number1-2
StatePublished - Oct 29 2004
Externally publishedYes


  • Calcium
  • Estrogen
  • Non-genomic effects
  • RN46A cells
  • Serotonin transporter

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology


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