ESTRADIOL EFFECTS ON LEPTIN EXPRESSION IS MEDIATED BY THE INTERRELATIONSHIP OF DIFFERENT TRANSCRIPTIONS FACTORS.

MARIA FERNANDA CAMISAY; VÍCTOR SÁNCHEZ MARGALET; MALENA SCHANTON; BERNARDO MASKIN; CECILIA L. VARONE; ANTONIO PÉREZ PÉREZ; ALEJANDRA ERLEJMAN

CABA

Congreso; LXII Reunión de la Sociedad Argentina de Investigación Clínica; 2017

628) ESTRADIOL EFFECTS ON LEPTIN EXPRESSIONIS MEDIATED BY THE INTERRELATIONSHIP OF DIFFERENTTRANSCRIPTIONS FACTORS.Malena Schanton (1), Maria Fernanda Camisay (1), AntonioPeréz Peréz (2), Bernardo Maskin (3), Victor Sanchez Margalet(2), Alejandra Giselle Erlejman (1), Cecilia Varone (1)(1) Departamento de Química Biológica, FCEN, UBA,IQUIBICEN, CONICET, Buenos Aires, Argentina. (2) Departamentode Bioquímica Médica y Biología Molecular, Universidadde Sevilla, Sevilla, España. (3) Hospital NacionalProfesor Alejandro Posadas, Buenos Aires, Argentina.Leptin is a key hormone in placental physiology. It regulatestrophoblast proliferation, inhibits apoptosis, stimulates protein synthesis,and regulates fetal growth and development. The mechanismsinvolved in the regulation of placental leptin expression arenot fully understood. Previous results from our lab demonstratedthat estradiol (E2) regulates leptin expression involving genomic andnon-genomic effects. In these study we aimed to analyze the effectof Sp1 and NFkB transcription factors and cAMP/PKA signalingpathways in the induction of leptin expression by E2 in human placentalcells. BeWo cells cultured under standard conditions, as wellsas human placental explants were used. Western blot, qRT-PCR,immunofluorescences, transfections assay with reporter constructsand expression vectors were carried out. We found that the inhibitionof the NFkB factor reduced the E2 action over the leptin expression(P£0,05), and the overexpression of the p65 subunit (Rel A)RESÚMENES DE LAS COMUNICACIONES 249significantly increases the transcriptional activity of leptin promoter(P£0,05). On the other hand, BeWo-Sh2 cells expressing an shRNAagainst ERapha protein, show no effect to E2 treatment nor withSP1 factor or with Rel A, which will suggest that theses factor requiresERalpha so it could exert its effects on E2 leptin expression.Moreover we observed that Sp1 (P£0,05) and cAMP-PKA (P£0,05)pathway increased leptin promoter activity, instead we can counterthis effect with the pharmacological inhibitors H89 (P£0,05) andSQ22536 (P£0,005). Finally by immunofluorescence we observedthat there is a strong correlation between the ERalpha and the p65subunit localization. These findings suggest that leptin expressionis tightly regulated and improved the comprehension of the mechanismswhere by E2 regulates leptin expression and leptin functionduring pregnancy.Keywords: Leptin, transcription factors, placenta