Serotonin and serotonin reuptake inhibitors alter placental aromatase

Publication date: Available online 8 September 2019Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): Andrée-Anne Hudon Thibeault, Yossef López de Los Santos, Nicolas Doucet, J. Thomas Sanderson, Cathy VaillancourtAbstractSerotonin reuptake inhibitors (SRIs) are currently the main molecules prescribed to pregnant women that suffer from depression. Placental cells are exposed to SRIs via maternal blood, and we have previously shown that SRIs alter feto-placental steroidogenesis in an in vitro co-culture model. More specifically, serotonin (5-HT) regulates the estrogen biosynthetic enzyme aromatase (cytochrome P450 19; CYP19), which is disrupted by fluoxetine and its active metabolite norfluoxetine in BeWo choriocarcinoma cells. Based on molecular simulations, the present study illustrates that the SRIs fluoxetine, norfluoxetine, paroxetine, sertraline, citalopram and venlafaxine exhibit binding affinity for the active-site pocket of CYP19, suggesting potential competitive inhibition. Using BeWo cells and primary villous trophoblast cells isolated from normal term placentas, we compared the effects of the SRIs on CYP19 activity. We observed that paroxetine and sertraline induce aromatase activity in BeWo cells, while venlafaxine, fluoxetine, paroxetine and sertraline decrease aromatase activity in primary villous trophoblast. The effects of the paroxetine and sertraline in primary villous trophoblasts were observed at the lower doses tested. We also s...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research