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

SHANTON M.; CAMISAY M.F.; PERÉZ PERÉZ A.; MASKIN B.; SANCHEZ MARGALET V.; ERLEJMAN, A.G.; VARONE C.

CABA

Congreso; LXII Reunión anual de la Sociedad Argentina de Investigación Clínica (SAIC) en el marco de la Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedad Argenitna de Investigación Clínica

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) significantly increases the transcriptional activity of leptin promoter (P<,05). On the other hand, BeWo-Sh2 cells expressing an shRNA against ERapha protein, show no effect to E2 treatment nor with SP1 factor or with Rel A, which will suggest that theses factor requires ERalpha 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 counter this effect with the pharmacological inhibitors H89 (P<0,05) and SQ22536 (P<0,005). Finally by immunofluorescence we observed that there is a strong correlation between the ERalpha and the p65 subunit localization. These findings suggest that leptin expressionis tightly regulated and improved the comprehension of the mechanisms where by E2 regulates leptin expression and leptin function during pregnancy