A link between Notch and progesterone maintains the functionality of the rat corpus luteum

ACCIALINI PAULA; HERNANDEZ FATIMA; BAS DIANA; PAZOS CAMILA; IRUSTA GRISELDA; ABRAMOVICH DALHIA; TESONE MARTA

REPRODUCTION

BIOSCIENTIFICA LTD

Año: 2015 vol. 149 p. 1 - 10

1470-1626

We investigated the interaction between the Notch pathway and progesterone (P) 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 P production, steroidogenic regulators, apoptotic parameters and signaling transduction pathways in cultures of CL isolated from pregnant and superovulated rats. We detected a decrease in P production when corpora lutea (CL) were incubated with DAPT, a gamma secretase inhibitor. This effect could be in part due to the decrease detected in the CL protein levels of P450scc since StAR and 3β-HSD were not affected by Notch inhibition. Besides, the addition of aminoglutethimide to the CL culture medium decreased NICD of NOTCH 1. We observed an increase in the expression of active CASPASE3 (CASP3) after Notch inhibition which was reversed by the presence of P. The BAX/BCLXL ratio was increased in CL treated with DAPT and the presence of P reversed this effect. In addition, AKT phosphorylation was inhibited in CL treated with DAPT but had no effect on ERK activation. To demonstrate that the action of DAPT is specifically related to the inhibition of Notch, CL were incubated with DLL4 antibody and a decrease in P production was detected. These results suggest the existence of a novel link between P and the Notch signaling pathway to maintain the functionality of the CL.