Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition assay and in the H295R cell assay

Naja Wessel Jacobsen, Cecilie Hurup Hansen, Christine Nellemann, Bjarne Styrishave, Bent Halling-Sørensen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Selective serotonin reuptake inhibitors are known to have a range of disorders that are often linked to the endocrine system e.g. hormonal imbalances, breast enlargement, sexual dysfunction, and menstrual cycle disorders. The mechanisms behind most of these disorders are not known in details. In this study we investigated whether the endocrine effect due to SSRI exposure could be detected in well adopted in vitro steroidogenesis assays, two versions of the aromatase enzyme inhibition assay and the H295R cell assay. The five drugs citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, were shown to inhibit the aromatase enzyme in both types of aromatase assays. The IC50 values ranged from 3 to 600μM. All five SSRIs, were further investigated in the H295R cell line. All compounds altered the steroid secretion from the cells, the lowest observed effect levels were 0.9μM and 3.1μM for sertraline and fluvoxamine, respectively. In general the H295R cell assay was more sensitive to SSRI exposure than the two aromatase assays, up to 20 times more sensitive. This indicates that the H295R cell line is a better tool for screening endocrine disrupting effects. Our findings show that the endocrine effects of SSRIs may, at least in part, be due to interference with the steroidogenesis.
Original languageEnglish
JournalToxicology in Vitro
Volume29
Issue number7
Pages (from-to)1729-1735
Number of pages7
ISSN0887-2333
DOIs
Publication statusPublished - 2015

Keywords

  • 17β-estradiol
  • Citalopram
  • Endocrine disruption
  • Fluoxetine
  • Fluvoxamine
  • Paroxetine
  • Progesterone
  • SSRI
  • Sertraline
  • Steroidogenesis
  • Testosterone

Cite this

Jacobsen, Naja Wessel ; Hansen, Cecilie Hurup ; Nellemann, Christine ; Styrishave, Bjarne ; Halling-Sørensen, Bent. / Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition assay and in the H295R cell assay. In: Toxicology in Vitro. 2015 ; Vol. 29, No. 7. pp. 1729-1735.
@article{7eb0d36006064515a3d4a55ff5950c10,
title = "Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition assay and in the H295R cell assay",
abstract = "Selective serotonin reuptake inhibitors are known to have a range of disorders that are often linked to the endocrine system e.g. hormonal imbalances, breast enlargement, sexual dysfunction, and menstrual cycle disorders. The mechanisms behind most of these disorders are not known in details. In this study we investigated whether the endocrine effect due to SSRI exposure could be detected in well adopted in vitro steroidogenesis assays, two versions of the aromatase enzyme inhibition assay and the H295R cell assay. The five drugs citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, were shown to inhibit the aromatase enzyme in both types of aromatase assays. The IC50 values ranged from 3 to 600μM. All five SSRIs, were further investigated in the H295R cell line. All compounds altered the steroid secretion from the cells, the lowest observed effect levels were 0.9μM and 3.1μM for sertraline and fluvoxamine, respectively. In general the H295R cell assay was more sensitive to SSRI exposure than the two aromatase assays, up to 20 times more sensitive. This indicates that the H295R cell line is a better tool for screening endocrine disrupting effects. Our findings show that the endocrine effects of SSRIs may, at least in part, be due to interference with the steroidogenesis.",
keywords = "17β-estradiol, Citalopram, Endocrine disruption, Fluoxetine, Fluvoxamine, Paroxetine, Progesterone, SSRI, Sertraline, Steroidogenesis, Testosterone",
author = "Jacobsen, {Naja Wessel} and Hansen, {Cecilie Hurup} and Christine Nellemann and Bjarne Styrishave and Bent Halling-S{\o}rensen",
year = "2015",
doi = "10.1016/j.tiv.2015.07.005",
language = "English",
volume = "29",
pages = "1729--1735",
journal = "Toxicology in Vitro",
issn = "0887-2333",
publisher = "Pergamon Press",
number = "7",

}

Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition assay and in the H295R cell assay. / Jacobsen, Naja Wessel; Hansen, Cecilie Hurup; Nellemann, Christine; Styrishave, Bjarne; Halling-Sørensen, Bent.

In: Toxicology in Vitro, Vol. 29, No. 7, 2015, p. 1729-1735.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition assay and in the H295R cell assay

AU - Jacobsen, Naja Wessel

AU - Hansen, Cecilie Hurup

AU - Nellemann, Christine

AU - Styrishave, Bjarne

AU - Halling-Sørensen, Bent

PY - 2015

Y1 - 2015

N2 - Selective serotonin reuptake inhibitors are known to have a range of disorders that are often linked to the endocrine system e.g. hormonal imbalances, breast enlargement, sexual dysfunction, and menstrual cycle disorders. The mechanisms behind most of these disorders are not known in details. In this study we investigated whether the endocrine effect due to SSRI exposure could be detected in well adopted in vitro steroidogenesis assays, two versions of the aromatase enzyme inhibition assay and the H295R cell assay. The five drugs citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, were shown to inhibit the aromatase enzyme in both types of aromatase assays. The IC50 values ranged from 3 to 600μM. All five SSRIs, were further investigated in the H295R cell line. All compounds altered the steroid secretion from the cells, the lowest observed effect levels were 0.9μM and 3.1μM for sertraline and fluvoxamine, respectively. In general the H295R cell assay was more sensitive to SSRI exposure than the two aromatase assays, up to 20 times more sensitive. This indicates that the H295R cell line is a better tool for screening endocrine disrupting effects. Our findings show that the endocrine effects of SSRIs may, at least in part, be due to interference with the steroidogenesis.

AB - Selective serotonin reuptake inhibitors are known to have a range of disorders that are often linked to the endocrine system e.g. hormonal imbalances, breast enlargement, sexual dysfunction, and menstrual cycle disorders. The mechanisms behind most of these disorders are not known in details. In this study we investigated whether the endocrine effect due to SSRI exposure could be detected in well adopted in vitro steroidogenesis assays, two versions of the aromatase enzyme inhibition assay and the H295R cell assay. The five drugs citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, were shown to inhibit the aromatase enzyme in both types of aromatase assays. The IC50 values ranged from 3 to 600μM. All five SSRIs, were further investigated in the H295R cell line. All compounds altered the steroid secretion from the cells, the lowest observed effect levels were 0.9μM and 3.1μM for sertraline and fluvoxamine, respectively. In general the H295R cell assay was more sensitive to SSRI exposure than the two aromatase assays, up to 20 times more sensitive. This indicates that the H295R cell line is a better tool for screening endocrine disrupting effects. Our findings show that the endocrine effects of SSRIs may, at least in part, be due to interference with the steroidogenesis.

KW - 17β-estradiol

KW - Citalopram

KW - Endocrine disruption

KW - Fluoxetine

KW - Fluvoxamine

KW - Paroxetine

KW - Progesterone

KW - SSRI

KW - Sertraline

KW - Steroidogenesis

KW - Testosterone

U2 - 10.1016/j.tiv.2015.07.005

DO - 10.1016/j.tiv.2015.07.005

M3 - Journal article

VL - 29

SP - 1729

EP - 1735

JO - Toxicology in Vitro

JF - Toxicology in Vitro

SN - 0887-2333

IS - 7

ER -