Intracellular signaling involved in estrogen regulation of serotonin reuptake

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

doi:10.1016/j.mce.2004.07.017

Intracellular signaling involved in estrogen regulation of serotonin reuptake

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

Pharmacology & Toxicology

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

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 language	English (US)
Pages (from-to)	33-42
Number of pages	10
Journal	Molecular and Cellular Endocrinology
Volume	226
Issue number	1-2
DOIs	https://doi.org/10.1016/j.mce.2004.07.017
State	Published - Oct 29 2004

Keywords

Calcium
Estrogen
Non-genomic effects
RN46A cells
Serotonin transporter

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Endocrinology

Access to Document

10.1016/j.mce.2004.07.017

Cite this

@article{ce29d3f1053a44e48d57fe6940ab139b,

title = "Intracellular signaling involved in estrogen regulation of serotonin reuptake",

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.",

keywords = "Calcium, Estrogen, Non-genomic effects, RN46A cells, Serotonin transporter",

author = "Nina Koldzic-Zivanovic and Seitz, \{Patricia K.\} and Watson, \{Cheryl S.\} and Cunningham, \{Kathryn A.\} and Thomas, \{Mary L.\}",

note = "Funding Information: We would like to thank Dr. Scott Whittemore for providing RN46A cells and Dr. Leoncio Vergara for his help with Ca 2+ measurement experiments. This research was supported by NIDA grants DA11428 and DA00260.",

year = "2004",

month = oct,

day = "29",

doi = "10.1016/j.mce.2004.07.017",

language = "English (US)",

volume = "226",

pages = "33--42",

journal = "Molecular and Cellular Endocrinology",

issn = "0303-7207",

publisher = "Elsevier Ireland Ltd",

number = "1-2",

}

TY - JOUR

T1 - Intracellular signaling involved in estrogen regulation of serotonin reuptake

AU - Koldzic-Zivanovic, Nina

AU - Seitz, Patricia K.

AU - Watson, Cheryl S.

AU - Cunningham, Kathryn A.

AU - Thomas, Mary L.

N1 - Funding Information: We would like to thank Dr. Scott Whittemore for providing RN46A cells and Dr. Leoncio Vergara for his help with Ca 2+ measurement experiments. This research was supported by NIDA grants DA11428 and DA00260.

PY - 2004/10/29

Y1 - 2004/10/29

N2 - 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.

AB - 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.

KW - Calcium

KW - Estrogen

KW - Non-genomic effects

KW - RN46A cells

KW - Serotonin transporter

UR - https://www.scopus.com/pages/publications/5644294412

UR - https://www.scopus.com/pages/publications/5644294412#tab=citedBy

U2 - 10.1016/j.mce.2004.07.017

DO - 10.1016/j.mce.2004.07.017

M3 - Article

C2 - 15489003

AN - SCOPUS:5644294412

SN - 0303-7207

VL - 226

SP - 33

EP - 42

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

IS - 1-2

ER -

Intracellular signaling involved in estrogen regulation of serotonin reuptake

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this