Intracellular signaling involved in estrogen regulation of serotonin reuptake

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

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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
Volume226
Issue number1-2
DOIs
StatePublished - Oct 29 2004

Fingerprint

Estrogen Receptors
Serotonin
Serotonin Plasma Membrane Transport Proteins
Estrogens
Estradiol
Selective Estrogen Receptor Modulators
Serotonin Receptors
Tamoxifen
Progesterone
Testosterone
Rats
Steroids
Cells
Cell Line
fulvestrant
Estrogen Receptor Antagonists

Keywords

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

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Intracellular signaling involved in estrogen regulation of serotonin reuptake. / Koldzic-Zivanovic, Nina; Seitz, Patricia K.; Watson, Cheryl S.; Cunningham, Kathryn; Thomas, Mary L.

In: Molecular and Cellular Endocrinology, Vol. 226, No. 1-2, 29.10.2004, p. 33-42.

Research output: Contribution to journalArticle

Koldzic-Zivanovic, Nina ; Seitz, Patricia K. ; Watson, Cheryl S. ; Cunningham, Kathryn ; Thomas, Mary L. / Intracellular signaling involved in estrogen regulation of serotonin reuptake. In: Molecular and Cellular Endocrinology. 2004 ; Vol. 226, No. 1-2. pp. 33-42.
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