NFkB Effects on Estradiol Induced Placental Leptin Expression

YESICA GAMBINO; CECILIA VARONE; SCHANTON MALENA; BERNARDO MASKIN; A. PEREZ PEREZ; V. SANCHEZ MARGALET

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC), LXIV Reunión Anual de la Sociedad Argentina de Inmunología (SAI), XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE), VII Reunión Cient; 2016

Leptin is a key hormone in placental physiology. Previous results from our lab demonstrated that estradiol (E2) regulates leptin expression involving genomic and non-genomic effects. Considering these results and that we have seen through an in silico analysis on the promoter sequence of leptin gene, that there is a potential binding site for NFkB between -2850 and -2838bp, and taking into account the interaction that takes among the ERs and the NFkB factor, we decided to analyze the involvement of this transcription factor in the effects of E2 on the expression of placental leptin.The BeWo cells were transiently transfected with the Rel A vector which express the subunit p65, one of the responsible for the activity of NFkB dimers. The expression of this protein decreased significantly E2 effects on the transcriptional activity of pL1951 vector. Is also observed a markedly activity reduced of the basal leptin promoter. Similar results can be seen with the BeWo-Sh2, treated with doxiciclina, which presents reduced level of Erα protein. Suggesting that the overexpression of Rel A would inhibit the interaction of others factors with there regulators sequence on the leptin promoter, one of those affected factor it could be the ERs receptors.Experiments with placental explants and BeWo cells where perform treated with E2 for 48 hours in presence of sulfasalazine (an Ikk inhibitor, the activating kinase of NFkB), later analyzed the expression of endogen leptin by western blot and the messenger by RT-PCR, the obtain results shows that the treatment with the drug reduce the E2 action over the endogenous leptin expression, suggesting the participation of the NFkB dimers in the regulatory effect from this steroid.These results provide new evidence about the mechanisms by which the E2 regulates the expression of placental leptin.