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Anandamide targets aromatase: A breakthrough on human decidualization.
Biochim Biophys Acta Mol Cell Biol Lipids. 2019 12; 1864(12):158512.BB

Abstract

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 (E2) and progesterone. E2 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, E2 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 E2 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.

Authors+Show Affiliations

UCIBIO, REQUIMTE, Laboratório de Bioquímica, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Portugal.UCIBIO, REQUIMTE, Laboratório de Bioquímica Computacional, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Portugal.UCIBIO, REQUIMTE, Laboratório de Bioquímica, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Portugal.UCIBIO, REQUIMTE, Laboratório de Bioquímica Computacional, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Portugal.UCIBIO, REQUIMTE, Laboratório de Bioquímica Computacional, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Portugal.UCIBIO, REQUIMTE, Laboratório de Bioquímica, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Portugal.UCIBIO, REQUIMTE, Laboratório de Bioquímica, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Portugal.UCIBIO, REQUIMTE, Laboratório de Bioquímica, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Portugal. Electronic address: natercia@ff.up.pt.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31454668

Citation

Almada, Marta, et al. "Anandamide Targets Aromatase: a Breakthrough On Human Decidualization." Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids, vol. 1864, no. 12, 2019, p. 158512.
Almada M, Oliveira A, Amaral C, et al. Anandamide targets aromatase: A breakthrough on human decidualization. Biochim Biophys Acta Mol Cell Biol Lipids. 2019;1864(12):158512.
Almada, M., Oliveira, A., Amaral, C., Fernandes, P. A., Ramos, M. J., Fonseca, B., Correia-da-Silva, G., & Teixeira, N. (2019). Anandamide targets aromatase: A breakthrough on human decidualization. Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids, 1864(12), 158512. https://doi.org/10.1016/j.bbalip.2019.08.008
Almada M, et al. Anandamide Targets Aromatase: a Breakthrough On Human Decidualization. Biochim Biophys Acta Mol Cell Biol Lipids. 2019;1864(12):158512. PubMed PMID: 31454668.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anandamide targets aromatase: A breakthrough on human decidualization. AU - Almada,Marta, AU - Oliveira,Ana, AU - Amaral,Cristina, AU - Fernandes,Pedro Alexandrino, AU - Ramos,Maria João, AU - Fonseca,Bruno, AU - Correia-da-Silva,Georgina, AU - Teixeira,Natercia, Y1 - 2019/08/24/ PY - 2019/01/04/received PY - 2019/07/08/revised PY - 2019/08/21/accepted PY - 2019/8/28/pubmed PY - 2020/2/28/medline PY - 2019/8/28/entrez KW - Anandamide KW - Aromatase KW - Decidualization KW - Endocrine regulation KW - Estradiol SP - 158512 EP - 158512 JF - Biochimica et biophysica acta. Molecular and cell biology of lipids JO - Biochim Biophys Acta Mol Cell Biol Lipids VL - 1864 IS - 12 N2 - 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 (E2) and progesterone. E2 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, E2 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 E2 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. SN - 1879-2618 UR - https://www.unboundmedicine.com/medline/citation/31454668/Anandamide_targets_aromatase:_A_breakthrough_on_human_decidualization_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1388-1981(19)30152-0 DB - PRIME DP - Unbound Medicine ER -