Highlights
· The effects of 5 SSRIs on steroid production were investigated in two aromatase assays and in the H295R cell assay.
· In both aromatase assays, all 5 SSRIs were shown to inhibit the aromatase enzyme.
· All 5 compounds altered the steroid production in the H295R cell assay.
· The IC50 values for the two aromatase assays were up to 20 times higher than for the H295R assay.
· The study indicates that the H295R assay is a more sensitive end point than the aromatase assays.
Jacobsen NW, Hansen CH, Nellemann C, Styrishave B, Halling-Sorensen B. 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. Toxicol In Vitro. https://www.sciencedirect.com/science/article/pii/S0887233315001666
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 600 muM.
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 0.9 muM and 3.1 muM 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.
· The effects of 5 SSRIs on steroid production were investigated in two aromatase assays and in the H295R cell assay.
· In both aromatase assays, all 5 SSRIs were shown to inhibit the aromatase enzyme.
· All 5 compounds altered the steroid production in the H295R cell assay.
· The IC50 values for the two aromatase assays were up to 20 times higher than for the H295R assay.
· The study indicates that the H295R assay is a more sensitive end point than the aromatase assays.
Jacobsen NW, Hansen CH, Nellemann C, Styrishave B, Halling-Sorensen B. 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. Toxicol In Vitro. https://www.sciencedirect.com/science/article/pii/S0887233315001666
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 600 muM.
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 0.9 muM and 3.1 muM 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.
