A link between Notch and progesterone maintains the functionality of the rat corpus luteum
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 effe...
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todo:paper_14701626_v149_n1_p1_Accialini2023-10-03T16:17:37Z A link between Notch and progesterone maintains the functionality of the rat corpus luteum Accialini, P. Hernández, S.F. Bas, D. Pazos, M.C. Irusta, G. Abramovich, D. Tesone, M. 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 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:BCLX<inf>L</inf> 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. Fil:Accialini, P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Hernández, S.F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Irusta, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Abramovich, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Tesone, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_14701626_v149_n1_p1_Accialini |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
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 |
spellingShingle |
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 Accialini, P. Hernández, S.F. Bas, D. Pazos, M.C. Irusta, G. Abramovich, D. Tesone, M. A link between Notch and progesterone maintains the functionality of the rat corpus luteum |
topic_facet |
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 |
description |
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:BCLX<inf>L</inf> 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. |
format |
JOUR |
author |
Accialini, P. Hernández, S.F. Bas, D. Pazos, M.C. Irusta, G. Abramovich, D. Tesone, M. |
author_facet |
Accialini, P. Hernández, S.F. Bas, D. Pazos, M.C. Irusta, G. Abramovich, D. Tesone, M. |
author_sort |
Accialini, P. |
title |
A link between Notch and progesterone maintains the functionality of the rat corpus luteum |
title_short |
A link between Notch and progesterone maintains the functionality of the rat corpus luteum |
title_full |
A link between Notch and progesterone maintains the functionality of the rat corpus luteum |
title_fullStr |
A link between Notch and progesterone maintains the functionality of the rat corpus luteum |
title_full_unstemmed |
A link between Notch and progesterone maintains the functionality of the rat corpus luteum |
title_sort |
link between notch and progesterone maintains the functionality of the rat corpus luteum |
url |
http://hdl.handle.net/20.500.12110/paper_14701626_v149_n1_p1_Accialini |
work_keys_str_mv |
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