Regulation of leptin expression by 17beta-estradiol in human placental cells involves membrane associated estrogen receptor alpha.
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 17β-estradiol (E(2)) 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 E(2) 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, suggesting that E(2) also exerts its effects through membrane receptors. Moreover E-BSA rapidly activated different MAPKs and AKT pathways, and these pathways were involved in E(2) induced placental leptin expression. On the other hand we demonstrated the presence of ERα associated to the plasma membrane of BeWo cells. We showed that E(2) genomic and nongenomic actions could be mediated by ERα. Supporting this idea, the downregulation of ERα level through a specific siRNA, decreased E-BSA effects on leptin expression. Taken together, these results provide new evidence of the mechanisms whereby E(2) regulates leptin expression in placenta and support the importance of leptin in placental physiology.
Departamento de Química Biológica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Yésica P
YP
Gambino
Antonio
A
Pérez Pérez
José L
JL
Dueñas
Juan Carlos
JC
Calvo
Víctor
V
Sánchez-Margalet
Cecilia L
CL
Varone
D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D000077267:Fulvestrant; D005786:Gene Expression Regulation / Q000187:drug effects*; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D020738:Leptin / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D010920:Placenta / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D012710:Serum Albumin, Bovine; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D020738:Leptin; D000077267:Fulvestrant; D012710:Serum Albumin, Bovine; D004958:Estradiol