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Anandamide targets aromatase: A breakthrough on human decidualization

Title
Anandamide targets aromatase: A breakthrough on human decidualization
Type
Article in International Scientific Journal
Year
2019
Authors
Almada, M
(Author)
Other
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Oliveira, A
(Author)
Other
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Amaral, C
(Author)
Other
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Ramos, MJ
(Author)
FCUP
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Georgina Correia da Silva
(Author)
FFUP
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Journal
Vol. 1864
ISSN: 1388-1981
Publisher: Elsevier
Other information
Authenticus ID: P-00R-1K1
Abstract (EN): In each menstrual cycle endometrial stromal cells (hESC) proliferate and differentiate into specialized decidual cells, a process termed decidualization, which regulates endometrial receptivity. Decidualization is mainly controlled by sex ovarian hormones, estradiol (E-2) and progesterone. E-2 plays an important role in the expression of the progesterone receptor and promotes the endometrial stromal cells differentiation. Our group previously reported that anandamide (AEA) impairs decidualization through cannabinoid receptor 1 (CB1). In this study, we hypothesized whether AEA inhibitory effect on cell decidualization could be mediated through interaction with aromatase and consequent interference in estradiol production/signaling. We used an immortalized human endometrial stromal cell line (St-T1b) and human decidual fibroblasts (HdF) derived from human term placenta. In cells exposed to a differentiation stimulus, AEA-treatment prevents the increase of the expression of CYP19A1 gene encoding aromatase, E-2 levels and of estradiol receptor expression, that are observed in differentiating cells. Regarding CYP19A1 mRNA levels, the effect was partially reverted by a CB1 receptor antagonist and by a COX2 inhibitor. In addition, we report that AEA presents anti-aromatase activity in placental microsomes, the nature of the inhibition being the uncommon mixed type as revealed by the kinetic studies. Structural analysis of the AEA-Aromatase complexes determined that AEA may bind to the active site pocket of the enzyme. In overall we report that AEA inhibits aromatase activity and may affect E-2 signaling crucial for the decidualization process, indicating that a deregulation of the endocannabinoid system may be implicated in endometrial dysfunction and in fertility/infertility disorders.
Language: English
Type (Professor's evaluation): Scientific
No. of pages: 9
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