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Selective Serotonin-Reuptake Inhibitors Alter Aromatase Activity In Trophoblast Cells

Hudon-Thibeault, Andrée-Anne; Sanderson, J. Thomas; Vaillancourt, Cathy . Selective Serotonin-Reuptake Inhibitors Alter Aromatase Activity In Trophoblast Cells In: IFPA 2018: Clinical Growth via Placenta, September 25-28 2018, Tokyo, Japan.

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Résumé

Objectives: Selective serotonin-reuptake inhibitors (SSRIs) are the mainpharmacological treatment prescribed to depressive pregnant women. Wehave previously shown that serotonin (5-HT), via the 5-HT2Areceptor,regulates the estrogen biosynthetic enzyme aromatase (CYP19), in BeWo and JEG-3 cells. Moreover, we have shown that the SSRIfluoxetine and itsmetabolite norfluoxetine disrupt CYP19 activity in BeWo cells. Here, theobjective was to compare the effects of different SSRIs on placental CYP19activity. We hypothesized that SSRIs, by their serotonergic action induceplacental CYP19 activity.

Methods: BeWo cell line and primary villous cytotrophoblast cells isolatedfrom normal term placentas were treated for 24 h to several concentra-tions of 5-HT, 5-HT2A-receptor agonist 2,5-dimethoxy-4-iodoamphet-amine (DOI) or SSRIs (fluoxetine, norfluoxetine, paroxetine, sertraline,citalopram and venlafaxine). Aromatase activity was determined by triti-ated-water release assay.

Results: As previously shown in BeWo cells, 5-HTand DOI increased CYP19activity in primary cytotrophoblasts (162% and 200 %, respectively, at 1mM). In BeWo cells, CYP19 activity was increased by paroxetine (168% and185% at 1 and 3mM) and sertraline (270% at 1mM), while citalopram andvenlafaxine had no effect. In primary cultures, CYP19 activity wasdecreased byfluoxetine (by 13% at 0.3mM), paroxetine (by 34% and 41% at0.03 and 0.1mM), sertraline (by 33% at 0.03mM), venlafaxine (31% at 1mM),while the other SSRIs had no effect.

Conclusion: This study indicates that 5-HT and 5-HT2A-receptor stim-ulation increase placental CYP19 activity, whereas the effects of SSRIs onCYP19 are unlikely solely attributable to inhibition of 5-HT transportsince they vary depending on the molecule. Differences between BeWoand primary cytotrophoblast cells in response to SSRIs indicate differentmechanisms of CYP19 regulation, suggesting that the choice oftrophoblast model for placental steroidogenesis studies should be takencarefully.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Affiche scientifique P2.47
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 07 août 2019 15:35
Dernière modification: 07 août 2019 15:35
URI: http://espace.inrs.ca/id/eprint/8129

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