Augmentation of leptin synthesis and secretion through activation of protein kinases A and C in cultured human trophoblastic cells.
Leptin is a fat cell-derived hormone that regulates food intake and energy expenditure. We previously demonstrated that leptin is produced by nonadipose cells, i.e. by placental trophoblasts. We also reported that a human trophoblastic cell line, BeWo cells, expresses leptin gene and secretes leptin into culture media. To elucidate the regulatory mechanisms of leptin production by human trophoblasts, we investigated synthesis and secretion of leptin in BeWo cells and in explant cultures of human placental tissue. Leptin production and gene expression in BeWo cells were increased by treatment with forskolin. The forskolin-induced increase in leptin production was completely suppressed by H89, an inhibitor of protein kinase A. Leptin production and gene expression in BeWo cells were increased by treatment with phorbol myristate acetate (PMA). The PMA-induced increase in leptin production was completely suppressed by H7 and staurosporine, both of which are inhibitors of protein kinase C. Leptin secretion from first trimester chorionic tissue was approximately 50-fold greater than that from term placental tissue. Leptin production and gene expression in explant cultures of placental tissue at both stages of pregnancy were augmented markedly by treatment with forskolin or PMA. The present study demonstrated augmentation of leptin production by protein kinase A and protein kinase C in cultured human trophoblasts, thereby leading to a better understanding of the regulatory mechanisms of leptin production in human trophoblasts in vivo.
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Japan.
S
S
Yura
N
N
Sagawa
Y
Y
Ogawa
H
H
Masuzaki
H
H
Mise
T
T
Matsumoto
K
K
Ebihara
S
S
Fujii
K
K
Nakao
D002460:Cell Line; D002823:Chorion / Q000378:metabolism; D002845:Chromatography; D005576:Colforsin / Q000494:pharmacology; D003470:Culture Media / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006801:Humans; D020738:Leptin; D009994:Osmolar Concentration; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D011493:Protein Kinase C / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*
D003470:Culture Media; D020738:Leptin; D011506:Proteins; D012333:RNA, Messenger; D005576:Colforsin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate