CONICET | Buscador de Institutos y Recursos Humanos

Objective: Leptin, the 16000 MW protein product of the obese gene, was originally considered as an adipocyte-derived signaling molecule for the central control of metabolism. However, leptin has been suggested to be involved in other functions during pregnancy, particularly in placenta, where it was found to be expressed. Recently, we have demonstrated that leptin promotes proliferation and survival of trophoblastic cells. We also showed that leptin expression is tightly regulated by different important molecules in pregnancy, such as hCG, cAMP and estradiol. In different pathologies associated with reproduction, leptin expression level changes dramatically, but little has been described on its mechanisms of action and regulation. In the present work we aimed to study the regulation of leptin expression by hCG and cAMP in normal and pathological placentas. Methods: JEG-3 cells, cultured under standard conditions, as well as human placenta explants were used. Western blot analyses were carried out to detect leptin expression as well as the phosphorylated form of the ERK1/2 protein. Real time-PCR was also used to detect leptin expression. Results: We observed by Western blot and qRT-PCR that leptin expression is increased in pathological placentas compared with normal ones. Moreover we determined that the regulation of leptin expression by hCG (0-100 IU/ml) and cAMP (0-1mM) is lost in placentas from different pathologies (gestational diabetes, IUGR, preeclampsia). In these cases, leptin expression was significantly lower in pathological placentas than in normal placentas at term. Evenmore, ERK 1/2 phosphorylation is stimulated by hCG in normal placental explants and this effect disappears in placentas from pathological pregnancies. Conclusion: These results improve the comprehension of leptin function during pregnancy and further support the importance of leptin in the biology of reproduction.

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