Anandamide targets aromatase: A breakthrough on human decidualization

• Tipo: Artigo em Revista Científica Internacional
• Data: 2019

Autores

Almada, M (Autor) Outra; Oliveira, A (Autor) Outra; Amaral, C (Autor) Outra; Pedro A Fernandes (Autor) FCUP; Ramos, MJ (Autor) FCUP; Fonseca, BM (Autor) FFUP; Georgina Correia da Silva (Autor) FFUP; Teixeira, NA (Autor) FFUP

Revista

Título: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

Vol. 1864

ISSN: 1388-1981

Editora: Elsevier

Indexação

ISI Web of Knowledge - 14 Citações

Scopus - 18 Citações

Outras Informações

ID Authenticus: P-00R-1K1

DOI: 10.1016/j.bbalip.2019.08.008

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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9