ArticleClujul medical (1957)2015
In vitro modulation of estrogen receptor activity by norfluoxetine.
Article in Clujul medical (1957), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 10 citations in OpenAlex.
- Developmental Fluoxetine Exposure Alters Behavior and Neuropeptide Receptors in the Prairie Vole.Frontiers in behavioral neuroscience · 2020Article
- Serotonin and serotonin reuptake inhibitors alter placental aromatase.The Journal of steroid biochemistry and molecular biology · 2019Article
- Chronic Treatment with Fluoxetine Induces Sex-Dependent Analgesic Effects and Modulates HDAC2 and mGlu2 Expression in Female Mice.Frontiers in pharmacology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsSelective serotonin reuptake inhibitors (SSRIs) are antidepressants increasingly prescribed for pregnancy and postpartum depression. However, these compounds can cross the placenta and also pass into breast milk, thus reaching the fetus and infant during critical developmental stages, potentially causing adverse effects. Fluoxetine, a widely used SSRI, has been shown to affect (neuro)endocrine signaling in various organisms, including humans. This compound can also interact with estrogen receptors in vitro and cause an estrogen-dependent uterotrophic response in rodents. Consequently, the aim of the present study was to assess if the active metabolite of fluoxetine, namely norfluoxetine (NFLX), shares the same capacity for estrogen receptor interaction.
methodsThe in vitro (anti)estrogenic activity of norfluoxetine was assessed using a firefly luciferase reporter construct in the T47D-Kbluc breast cancer cell line. These cells express nuclear estrogen receptors (ERs) that can activate the transcription of the luciferase reporter gene upon binding of ER agonists. Light emission was monitored in case of cells exposed to norfluoxetine or mixtures of norfluoxetine-estradiol. Cell viability was assessed using a resazurin-based assay.
resultsDuring individual testing, NFLX was able to induce a significant increase in luciferase activity compared to control, but only at the highest concentration tested (10 μM). In binary mixtures with estradiol (30 pM constant concentration) a significant increase in luminescence was observed at low submicromolar norfluoxetine concentrations compared to estradiol alone.
conclusionNorfluoxetine can induce estrogenic effects in vitro and can potentiate the activity of estradiol. However, further studies are needed to clarify if these observed estrogenic effects may have detrimental consequences for human exposure.
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Registered trials
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