Regulation of leptin expression by 17beta-estradiol in human placental cells involves membrane associated estrogen receptor alpha

YESICA GAMBINO; ANTONIO PÉREZ-PÉREZ; JOSÉ; DUEÑAS; JUAN CARLOS CALVO; VÍCTOR SÁNCHEZ-MARGALET; CECILIA L. VARONE

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

ELSEVIER SCIENCE BV

Lugar: Londres; Año: 2012 vol. 1823 p. 900 - 910

0167-4889

The placenta produces a wide number of molecules that play essential roles in the establishment and maintenance of pregnancy. In this context, leptin has emerged as an important player in reproduction. The synthesis of leptin in normal trophoblastic cells is regulated by different endogenous biochemical agents, but the regulation of placental leptin expression is still poorly understood. We have previously reported that 17â- estradiol (E2) up-regulates placental leptin expression. To improve the understanding of estrogen receptor mechanisms in regulating leptin gene expression, in the current study we examined the effect of membrane-constrained E2 conjugate, E-BSA, on leptin expression in human placental cells. We have found that leptin expression was induced by E-BSA both in BeWo cells and human placental explants, suggestingthat E2 also exerts its effects through membrane receptors. Moreover E-BSA rapidly activated different MAPKs and AKT pathways, and these pathways were involved in E2 induced placental leptin expression. On the other hand we demonstrated the presence of ERá associated to the plasma membrane of BeWo cells. We showed that E2 genomic and nongenomic actions could be mediated by ERá. Supporting this idea, the downregulation of ERá level through a specific siRNA, decreased E-BSA effects on leptin expression. Taken together, these results provide new evidence of the mechanisms whereby E2 regulates leptin expression in placenta and support the importance of leptin in placental physiology.