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Abstract:

In this study, we investigated the interaction between the Notch pathway and progesterone to maintain the functionality of the corpus luteum (CL). When Notch signaling is activated, the γ-secretase complex releases the active intracellular domains (NICD) of their receptors, which exert survival effects. We designed studies to analyze whether the in vitro inhibition of Notch affects progesterone production, steroidogenic regulators, apoptotic parameters, and signaling transduction pathways in the cultures of CL isolated from pregnant and superovulated rats. We detected a decrease in progesterone production when corpora lutea (CL) were incubated with N-(N-(3,5-difluorophenacetyl-L-alanyl))-S-phenylglycine t-butyl ester (DAPT), a γ-secretase inhibitor. This effect could be in part due to the decrease detected in the CL protein levels of P450scc because STAR and 3β-hydroxysteroid dehydrogenase were not affected by Notch inhibition. Besides, the addition of aminoglutethimide to the CL culture medium decreased NICD of NOTCH1. We observed an increase in the expression of active CASPASE3 (CASP3) after in hibition by Notch, which was reversed bythe presence of progesterone. The BAX:BCLXL ratio was increased in CL treated with DAPT and the presence of progesterone reversed this effect. In addition, phosphorylation of AKT was in hibited in CL treated with DAPT, but had no effecton ERK activation. To demon strate that the action of DAPT is specifically related with the inhibition of Notch, CLs were incubated with DLL4 antibody and a decrease in progesterone production was detected. These results suggest the existence of a novel link between progesterone and the Notch signaling pathway to maintain the functionality of the CL. © 2015 Society for Reproduction and Fertility.

Registro:

Documento: Artículo
Título:A link between Notch and progesterone maintains the functionality of the rat corpus luteum
Autor:Accialini, P.; Hernández, S.F.; Bas, D.; Pazos, M.C.; Irusta, G.; Abramovich, D.; Tesone, M.
Filiación:Instituto de Biología y Medicina Experimental (IByME-CONICET), Vuelta de Obligado 2490, Buenos Aires, 1428, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:3(or 17)beta hydroxysteroid dehydrogenase; aminoglutethimide; beta actin; Notch receptor; progesterone; protein Bax; protein bcl x; caspase 3; progesterone; adult; apoptosis; Article; corpus luteum; culture medium; enzyme phosphorylation; female; immunohistochemistry; immunoreactivity; in vitro study; luteal cell; nonhuman; ovary follicle; progesterone synthesis; rat; room temperature; stimulation; Western blotting; animal; cell culture; comparative study; corpus luteum; cytology; drug effects; enzyme immunoassay; metabolism; ovulation; phosphorylation; pregnancy; radioimmunoassay; signal transduction; Sprague Dawley rat; Rattus; Animals; Apoptosis; Blotting, Western; Caspase 3; Cells, Cultured; Corpus Luteum; Female; Immunoenzyme Techniques; Ovulation; Phosphorylation; Pregnancy; Progesterone; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Receptors, Notch; Signal Transduction
Año:2015
Volumen:149
Número:1
Página de inicio:1
Página de fin:10
DOI: http://dx.doi.org/10.1530/REP-14-0449
Título revista:Reproduction
Título revista abreviado:Reproduction
ISSN:14701626
CODEN:RCUKB
CAS:3(or 17)beta hydroxysteroid dehydrogenase, 9015-81-0; aminoglutethimide, 125-84-8; progesterone, 57-83-0; caspase 3, 169592-56-7; Caspase 3; Progesterone; Receptors, Notch
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14701626_v149_n1_p1_Accialini

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Citas:

---------- APA ----------
Accialini, P., Hernández, S.F., Bas, D., Pazos, M.C., Irusta, G., Abramovich, D. & Tesone, M. (2015) . A link between Notch and progesterone maintains the functionality of the rat corpus luteum. Reproduction, 149(1), 1-10.
http://dx.doi.org/10.1530/REP-14-0449
---------- CHICAGO ----------
Accialini, P., Hernández, S.F., Bas, D., Pazos, M.C., Irusta, G., Abramovich, D., et al. "A link between Notch and progesterone maintains the functionality of the rat corpus luteum" . Reproduction 149, no. 1 (2015) : 1-10.
http://dx.doi.org/10.1530/REP-14-0449
---------- MLA ----------
Accialini, P., Hernández, S.F., Bas, D., Pazos, M.C., Irusta, G., Abramovich, D., et al. "A link between Notch and progesterone maintains the functionality of the rat corpus luteum" . Reproduction, vol. 149, no. 1, 2015, pp. 1-10.
http://dx.doi.org/10.1530/REP-14-0449
---------- VANCOUVER ----------
Accialini, P., Hernández, S.F., Bas, D., Pazos, M.C., Irusta, G., Abramovich, D., et al. A link between Notch and progesterone maintains the functionality of the rat corpus luteum. Reproduction. 2015;149(1):1-10.
http://dx.doi.org/10.1530/REP-14-0449