title: A link between Notch and progesterone maintains the functionality of the rat corpus luteum.
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 inhibition by Notch, which was reversed by the 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 inhibited in CL treated with DAPT, but had no effect on ERK activation. To demonstrate 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.
authors.affiliation: Instituto de Biología y Medicina Experimental (IByME-CONICET)Vuelta de Obligado 2490, Buenos Aires 1428, ArgentinaDepartamento de Química BiológicaFacultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: P
authors.initials: P
authors.lastname: Accialini
authors.affiliation: Instituto de Biología y Medicina Experimental (IByME-CONICET)Vuelta de Obligado 2490, Buenos Aires 1428, ArgentinaDepartamento de Química BiológicaFacultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: S F
authors.initials: SF
authors.lastname: Hernández
authors.affiliation: Instituto de Biología y Medicina Experimental (IByME-CONICET)Vuelta de Obligado 2490, Buenos Aires 1428, ArgentinaDepartamento de Química BiológicaFacultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: D
authors.initials: D
authors.lastname: Bas
authors.affiliation: Instituto de Biología y Medicina Experimental (IByME-CONICET)Vuelta de Obligado 2490, Buenos Aires 1428, ArgentinaDepartamento de Química BiológicaFacultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: M C
authors.initials: MC
authors.lastname: Pazos
authors.affiliation: Instituto de Biología y Medicina Experimental (IByME-CONICET)Vuelta de Obligado 2490, Buenos Aires 1428, ArgentinaDepartamento de Química BiológicaFacultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: G
authors.initials: G
authors.lastname: Irusta
authors.affiliation: Instituto de Biología y Medicina Experimental (IByME-CONICET)Vuelta de Obligado 2490, Buenos Aires 1428, ArgentinaDepartamento de Química BiológicaFacultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: D
authors.initials: D
authors.lastname: Abramovich
authors.affiliation: Instituto de Biología y Medicina Experimental (IByME-CONICET)Vuelta de Obligado 2490, Buenos Aires 1428, ArgentinaDepartamento de Química BiológicaFacultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina Instituto de Biología y Medicina Experimental (IByME-CONICET)Vuelta de Obligado 2490, Buenos Aires 1428, ArgentinaDepartamento de Química BiológicaFacultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina martatesone.uba@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Tesone
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D003338:Corpus Luteum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D007124:Immunoenzyme Techniques; D010060:Ovulation / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D051880:Receptors, Notch; D011374:Progesterone; D053148:Caspase 3