Ulipristal acetate interferes with actin remodeling induced by 17β-estradiol and progesterone in human endometrial stromal cells

Autores
Shortrede, Jorge Eduardo; Montt Guevara, Maria Magdalena; Pennacchio, Gisela Erika; Finiguerra, Michele; Giannini, Andrea; Genazzani, Alessandro D.; Simoncini, Tommaso
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Shortrede, Jorge Eduardo. Università degli Studi di Pisa; Italia
Fil: Montt Guevara, Maria Magdalena. Università degli Studi di Pisa; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pennacchio, Gisela Erika. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Finiguerra, Michele. Università degli Studi di Pisa; Italia
Fil: Giannini, Andrea. Università degli Studi di Pisa; Italia
Fil: Genazzani, Alessandro D.. Universita Degli Studi Di Modena E Reggio Emilia;
Fil: Simoncini, Tommaso. Università degli Studi di Pisa; Italia
Materia
17Β-ESTRADIOL (E2)
ACTIN REMODELING
ENDOMETRIAL STROMAL CELLS (ESC)
PROGESTERONE (P4)
ULIPRISTAL ACETATE (UPA)
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/90682
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/90682
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Ulipristal acetate interferes with actin remodeling induced by 17β-estradiol and progesterone in human endometrial stromal cellsShortrede, Jorge EduardoMontt Guevara, Maria MagdalenaPennacchio, Gisela ErikaFiniguerra, MicheleGiannini, AndreaGenazzani, Alessandro D.Simoncini, Tommaso17Β-ESTRADIOL (E2)ACTIN REMODELINGENDOMETRIAL STROMAL CELLS (ESC)PROGESTERONE (P4)ULIPRISTAL ACETATE (UPA)https://purl.org/becyt/ford/3.5https://purl.org/becyt/ford/3Ulipristal 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.Fil: Shortrede, Jorge Eduardo. Università degli Studi di Pisa; ItaliaFil: Montt Guevara, Maria Magdalena. Università degli Studi di Pisa; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pennacchio, Gisela Erika. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Finiguerra, Michele. Università degli Studi di Pisa; ItaliaFil: Giannini, Andrea. Università degli Studi di Pisa; ItaliaFil: Genazzani, Alessandro D.. Universita Degli Studi Di Modena E Reggio Emilia;Fil: Simoncini, Tommaso. Università degli Studi di Pisa; ItaliaFrontiers Research Foundation2018-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/90682Shortrede, Jorge Eduardo; Montt Guevara, Maria Magdalena; Pennacchio, Gisela Erika; Finiguerra, Michele; Giannini, Andrea; et al.; Ulipristal acetate interferes with actin remodeling induced by 17β-estradiol and progesterone in human endometrial stromal cells; Frontiers Research Foundation; Frontiers in Endocrinology; 9; JUL; 6-2018; 1-101664-2392CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fendo.2018.00350info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fendo.2018.00350/fullinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-29T11:40:25Zoai:ri.conicet.gov.ar:11336/90682instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-29 11:40:25.337CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Ulipristal acetate interferes with actin remodeling induced by 17β-estradiol and progesterone in human endometrial stromal cells
title Ulipristal acetate interferes with actin remodeling induced by 17β-estradiol and progesterone in human endometrial stromal cells
spellingShingle Ulipristal acetate interferes with actin remodeling induced by 17β-estradiol and progesterone in human endometrial stromal cells
Shortrede, Jorge Eduardo
17Β-ESTRADIOL (E2)
ACTIN REMODELING
ENDOMETRIAL STROMAL CELLS (ESC)
PROGESTERONE (P4)
ULIPRISTAL ACETATE (UPA)
title_short Ulipristal acetate interferes with actin remodeling induced by 17β-estradiol and progesterone in human endometrial stromal cells
title_full Ulipristal acetate interferes with actin remodeling induced by 17β-estradiol and progesterone in human endometrial stromal cells
title_fullStr Ulipristal acetate interferes with actin remodeling induced by 17β-estradiol and progesterone in human endometrial stromal cells
title_full_unstemmed Ulipristal acetate interferes with actin remodeling induced by 17β-estradiol and progesterone in human endometrial stromal cells
title_sort Ulipristal acetate interferes with actin remodeling induced by 17β-estradiol and progesterone in human endometrial stromal cells
dc.creator.none.fl_str_mv Shortrede, Jorge Eduardo
Montt Guevara, Maria Magdalena
Pennacchio, Gisela Erika
Finiguerra, Michele
Giannini, Andrea
Genazzani, Alessandro D.
Simoncini, Tommaso
author Shortrede, Jorge Eduardo
author_facet Shortrede, Jorge Eduardo
Montt Guevara, Maria Magdalena
Pennacchio, Gisela Erika
Finiguerra, Michele
Giannini, Andrea
Genazzani, Alessandro D.
Simoncini, Tommaso
author_role author
author2 Montt Guevara, Maria Magdalena
Pennacchio, Gisela Erika
Finiguerra, Michele
Giannini, Andrea
Genazzani, Alessandro D.
Simoncini, Tommaso
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv 17Β-ESTRADIOL (E2)
ACTIN REMODELING
ENDOMETRIAL STROMAL CELLS (ESC)
PROGESTERONE (P4)
ULIPRISTAL ACETATE (UPA)
topic 17Β-ESTRADIOL (E2)
ACTIN REMODELING
ENDOMETRIAL STROMAL CELLS (ESC)
PROGESTERONE (P4)
ULIPRISTAL ACETATE (UPA)
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.5
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Shortrede, Jorge Eduardo. Università degli Studi di Pisa; Italia
Fil: Montt Guevara, Maria Magdalena. Università degli Studi di Pisa; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pennacchio, Gisela Erika. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Finiguerra, Michele. Università degli Studi di Pisa; Italia
Fil: Giannini, Andrea. Università degli Studi di Pisa; Italia
Fil: Genazzani, Alessandro D.. Universita Degli Studi Di Modena E Reggio Emilia;
Fil: Simoncini, Tommaso. Università degli Studi di Pisa; Italia
description 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.
publishDate 2018
dc.date.none.fl_str_mv 2018-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/90682
Shortrede, Jorge Eduardo; Montt Guevara, Maria Magdalena; Pennacchio, Gisela Erika; Finiguerra, Michele; Giannini, Andrea; et al.; Ulipristal acetate interferes with actin remodeling induced by 17β-estradiol and progesterone in human endometrial stromal cells; Frontiers Research Foundation; Frontiers in Endocrinology; 9; JUL; 6-2018; 1-10
1664-2392
CONICET Digital
CONICET
url http://hdl.handle.net/11336/90682
identifier_str_mv Shortrede, Jorge Eduardo; Montt Guevara, Maria Magdalena; Pennacchio, Gisela Erika; Finiguerra, Michele; Giannini, Andrea; et al.; Ulipristal acetate interferes with actin remodeling induced by 17β-estradiol and progesterone in human endometrial stromal cells; Frontiers Research Foundation; Frontiers in Endocrinology; 9; JUL; 6-2018; 1-10
1664-2392
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fendo.2018.00350
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fendo.2018.00350/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Research Foundation
publisher.none.fl_str_mv Frontiers Research Foundation
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.10058

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