In vitro modulation of estrogen receptor activity by norfluoxetine

Authors

  • Diana Lupu
  • Anca Pop
  • Julien Cherfan
  • Béla Kiss
  • Felicia Loghin

DOI:

https://doi.org/10.15386/cjmed-476

Keywords:

norfluoxetine, estrogen receptors, in vitro

Abstract

Background & Aims: Selective 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, shares the same capacity for estrogen receptor interaction.

Materials and methods: The 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.

Results: During 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 (30pM constant concentration) a significant increase in luminescence was observed at low submicromolar norfluoxetine concentrations compared to estradiol alone.

Conclusion: Norfluoxetine 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.

Author Biographies

Diana Lupu, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca

Department of Toxicology

Anca Pop, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca

Department of Toxicology

Julien Cherfan, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca

Department of Toxicology

Béla Kiss, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca

Department of Toxicology

Felicia Loghin, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca

Department of Toxicology

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Published

2015-07-22

How to Cite

1.
Lupu D, Pop A, Cherfan J, Kiss B, Loghin F. In vitro modulation of estrogen receptor activity by norfluoxetine. Med Pharm Rep [Internet]. 2015 Jul. 22 [cited 2025 Oct. 5];88(3):386-90. Available from: https://medpharmareports.com/index.php/mpr/article/view/476

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Section

Original Research