Regulatory effects of estetrol on the endothelial plasminogen pathway and endothelial cell migration

Guevara, Maria Magdalena Montt; Palla, Giulia; Spina, Stefania; Bernacchi, Guja; Cecchi, Elena; Campelo, Adrián Esteban; Shortrede, Jorge Eduardo; Canu, Alessio; Simoncini, Tommaso

doi:10.1016/j.maturitas.2017.02.005

Cited by 16 publications

(7 citation statements)

References 24 publications

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“…Scratch Cell Migration Assay was performed with a plastic razor scrape as previously described Montt-Guevara et al ( 20 ). Briefly, a razor blade was pressed trough the confluent ESC monolayer to mark the starting line and cells were swept away on one side of the line.…”

Section: Methodsmentioning

confidence: 99%

Ulipristal Acetate Interferes With Actin Remodeling Induced by 17β-Estradiol and Progesterone in Human Endometrial Stromal Cells

et al. 2018

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Ulipristal acetate (UPA) is a selective progesterone receptor modulator (SPRM) used for emergency contraception and for the medical management of symptomatic uterine fibroids (UF). Treatment with UPA turns in amenorrhea and UF volume reduction. Treatment with UPA is associated with the frequent development of benign, transitory endometrial changes known as SPRM-associated endometrial changes (PAECs). Why PAECs develop and their biological or cellular basis is unknown. Sex steroids, including estrogen and progesterone, are established modulators of the actin cytoskeleton in various cells, including endometrial cells. This explains several morphological and functional changes in endometrial cells. We thus hypothesized that UPA may alter the appearance of the endometrium by interfering with the actions of 17β-estradiol (E2) or progesterone (P4) on actin dynamics. We isolated and cultured human endometrial stromal cells (ESC) from endometrial biopsies from healthy fertile women. Treatment with E2 or P4 stimulated visible actin rearrangements with actin remodeling toward the membrane. Activation through phosphorylation of the actin regulatory proteins, Moesin, and focal adhesion kinase (FAK), hacked actin remodeling induced by E2 and P4. Membrane re-localization of Paxillin and Vinculin were also induced by E2 and P4, showing the formation of focal adhesion complexes. All these E2 and P4 actions were inhibited by co-treatment with UPA, which was otherwise inactive if given alone. The cytoskeletal changes induced by E2 and P4 turned into increased motility of ESC, and UPA again blocked the actions E2 and P4. In conclusion, we find that UPA interferes with the cytoskeletal actions of E2 and P4 in ESC. This finding helps understanding the mode of actions of SPRMs in the endometrium and may be relevant for other potential clinical applications of UPA.

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Section: Methodsmentioning

confidence: 99%

Ulipristal Acetate Interferes With Actin Remodeling Induced by 17β-Estradiol and Progesterone in Human Endometrial Stromal Cells

et al. 2018

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“…In an in vitro study on human umbilical vein endothelial cells, the effects of E4 on fibrinolytic system and whether it could influence the ability of endothelial cells to migrate were studied [ 43 ]. Expression of plasminogen-activator inhibitor-1 (PAI-1), urokinase-type plasminogen activator (u-PA), and tissue plasminogen activator (t-PA) proteins were all increased by E4 in a dose-dependent manner, although E4 was less effective than equimolar amounts of E2.…”

Section: New Combined Hormonal Contraception With Estetrolmentioning

confidence: 99%

Estetrol: A New Choice for Contraception

Fruzzetti

Fidecicchi

Guevara

et al. 2021

JCM

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Estetrol (E4) is a natural estrogenic steroid that is normally produced by human fetal liver. Recent research has demonstrated that it is a potent, orally bioavailable, natural selective estrogen receptor modulator; it has a moderate affinity for both human estrogen receptor alpha (ERα) and ERβ, with a preference for ERα. Clinical studies have demonstrated possible use as an estrogen in combined oral contraceptives (COC). COCs containing E4 and drospirenone (DRSP) showed a high acceptability, tolerability, and user satisfaction also when compared to COCs containing ethinylestradiol (EE). E4/DRSP effectively inhibits ovulation, with a similar effect on endometrium thickness than that of EE-containing COCs. Low doses (15 mg) of E4 with DRSP (3 mg) showed promising results in term of bleeding pattern and cycle control, also when compared to other COCs containing synthetic estrogens. Moreover, the association has limited effects on serum lipids, liver, SHBG levels, and carbohydrate metabolism. This combination also could drive a lower risk of venous thromboembolism than EE-containing COCs. In this review, we will summarize the actual knowledge about the new E4-containing contraceptive. Further large-scale studies in the full target population are needed to provide more insights into the cardiovascular safety profile and user satisfaction of E4/DRSP.

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“…Previous studies confirmed that estrogen have a protective effect on vascular endothelial cells [21][22][23]. Endothelial dysfunction may contribute to acute kidney injury and acute cardiac injury in critically ill patients [24,25].…”

Section: <0001mentioning

confidence: 81%

Association of sex with clinical outcomes in COVID-19 patients: A retrospective analysis of 1190 cases

Liu

Zhang

Chen

et al. 2020

Respiratory Medicine

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Background: The outbreak of COVID-19 caused by SARS-CoV-2 has been a pandemic. The objective of our study was to explore the association between sex and clinical outcomes in patients with COVID-19. Methods: Detailed clinical data including clinical characteristics, laboratory tests, imaging features and treatments of 1190 cases of adult patients with confirmed COVID-19 were retrospectively analyzed. Associations between sex and clinical outcomes were identified by multivariable Cox regression analysis. Results: There were 635 (53.4%) male and 555 (46.6%) female patients in this study. Higher rates of acute kidney injury (5.5% vs. 2.9%, p = 0.026), acute cardiac injury (9.1% vs. 4.3%, p = 0.001), and disseminated intravascular coagulation (2.5% vs. 0.7%, P = 0.024) were observed in males. Compared with female patients, male patients with COVID-19 had a higher inhospital mortality rate (15.7% vs. 10.3%, p = 0.005). However, Cox regression analysis showed that sex did not influence inhospital mortality of COVID-19 patients. Conclusions: Male sex was associated with a worse prognosis of COVID-19, but it seems not to be an independent prognostic factor.

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Regulatory effects of estetrol on the endothelial plasminogen pathway and endothelial cell migration

Cited by 16 publications

References 24 publications

Ulipristal Acetate Interferes With Actin Remodeling Induced by 17β-Estradiol and Progesterone in Human Endometrial Stromal Cells

Ulipristal Acetate Interferes With Actin Remodeling Induced by 17β-Estradiol and Progesterone in Human Endometrial Stromal Cells

Estetrol: A New Choice for Contraception

Association of sex with clinical outcomes in COVID-19 patients: A retrospective analysis of 1190 cases

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