title: Cross talk between cAMP and p38 MAPK pathways in the induction of leptin by hCG in human placental syncytiotrophoblasts.
abstract: Leptin produced by the placental syncytiotrophoblasts participates in a number of processes in pregnancy including implantation, proliferation of the cytotrophoblasts, and nutrient transfer across the placenta. Despite the functional significance of leptin in pregnancy, the regulation of leptin synthesis is poorly understood in human placental syncytiotrophoblasts. In this study, we investigated the role of endogenous human chorionic gonadotropin (hCG) in the regulation of leptin production as well as the underlying mechanism involving the cross talk between cAMP and p38 mitogen-activated protein kinase (MAPK) pathways. We found that neutralization of endogenous hCG with its antibody dose dependently decreased leptin mRNA level and secretion, whereas exogenous hCG increased leptin mRNA level and secretion. Activation of the cAMP pathway with dibutyryl cAMP (db cAMP) or forskolin recapitulated the stimulatory effect of hCG on leptin expression. Inhibition of protein kinase A with H89 not only reduced the basal leptin expression but also attenuated the induced leptin expression by hCG. Treatment of the syncytiotrophoblasts with db cAMP and hCG phosphorylated p38 MAPK. Inhibition of p38 MAPK with SB203580 not only reduced the basal leptin production but also attenuated the leptin-induced production by both hCG and db cAMP. These data suggest that endogenous hCG plays a significant role in maintaining leptin production in human placental syncytiotrophoblasts, and this effect involves a cross talk between cAMP and p38 MAPK pathways.
authors.affiliation: Shanghai First Maternity and Infant Health Hospital, Tongji University, Shanghai 200040, People's Republic of China.
authors.forename: Y C
authors.initials: YC
authors.lastname: Ge
authors.forename: J N
authors.initials: JN
authors.lastname: Li
authors.forename: X T
authors.initials: XT
authors.lastname: Ni
authors.forename: C M
authors.initials: CM
authors.lastname: Guo
authors.forename: W S
authors.initials: WS
authors.lastname: Wang
authors.forename: T
authors.initials: T
authors.lastname: Duan
authors.forename: K
authors.initials: K
authors.lastname: Sun
mesh_terms: D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000242:Cyclic AMP / Q000819:agonists / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009994:Osmolar Concentration; D010766:Phosphorylation / Q000187:drug effects; D010920:Placenta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D047428:Protein Kinase Inhibitors / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015290:Second Messenger Systems / Q000187:drug effects; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D006063:Chorionic Gonadotropin; D020738:Leptin; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases