Up-Regulation of placental leptin by human chorionic gonadotropin

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Leptin, the 16,000 molecular weight protein product of the obese gene, was originally considered as an adipocyte-derived signaling moleculeforthe central control of metabolism. However, leptin has been suggested to be involved in other functions during pregnancy, particularly in placenta, in which i...

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Autores principales:	Maymó, J.L., Pérez, A.P., Sánchez-Margalet, V., Dueñas, J.L., Calvo, J.C., Varone, C.L.
Formato:	JOUR
Materias:	2 (2 amino 3 methoxyphenyl)chromone binding protein chorionic gonadotropin cyclic AMP cyclic AMP dependent protein kinase leptin luciferase mitogen activated protein kinase mitogen activated protein kinase 1 mitogen activated protein kinase 3 phosphatidylinositol 3 kinase recombinant chorionic gonadotropin wortmannin article cancer cell culture catalysis cell line cell stimulation choriocarcinoma DNA responsive element enzyme subunit explant genetic transfection hormonal regulation hormone response human human cell plasmid priority journal promoter region protein analysis protein expression protein phosphorylation reporter gene signal transduction trophoblast Western blotting
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00137227_v150_n1_p304_Maymo
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_00137227_v150_n1_p304_Maymo2023-10-03T14:11:20Z Up-Regulation of placental leptin by human chorionic gonadotropin Maymó, J.L. Pérez, A.P. Sánchez-Margalet, V. Dueñas, J.L. Calvo, J.C. Varone, C.L. 2 (2 amino 3 methoxyphenyl)chromone binding protein chorionic gonadotropin cyclic AMP cyclic AMP dependent protein kinase leptin luciferase mitogen activated protein kinase mitogen activated protein kinase 1 mitogen activated protein kinase 3 phosphatidylinositol 3 kinase recombinant chorionic gonadotropin wortmannin article cancer cell culture catalysis cell line cell stimulation choriocarcinoma DNA responsive element enzyme subunit explant genetic transfection hormonal regulation hormone response human human cell plasmid priority journal promoter region protein analysis protein expression protein phosphorylation reporter gene signal transduction trophoblast Western blotting Leptin, the 16,000 molecular weight protein product of the obese gene, was originally considered as an adipocyte-derived signaling moleculeforthe central control of metabolism. However, leptin has been suggested to be involved in other functions during pregnancy, particularly in placenta, in which it was found to be expressed. In the present work, we have found that recombinant human chorionic gonadotropin (hCG) added to BeWo choriocarcinoma cell line showed a stimulatory effect on endogenous leptin expression, when analyzed by Western blot. This effect was time and dose dependent. Maximal effect was achieved at hCG 100 IU/ml. Moreover, hCG treatment enhanced leptin promoter activity up to 12.9 times, evaluated by transient transfection with a plasmid construction containing different promoter regions and the reporter gene luciferase. This effect was dose dependent and evidenced with all the promoter regions analyzed, regardless of length. Similar results were obtained with placental explants, thus indicating physiological relevance. Because hCG signal transduction usually involves cAMP signaling, this pathway was analyzed. Contrarily, we found that dibutyryl cAMP counteracted hCG effect on leptin expression. Furthermore, cotransfection with the catalytic subunit of PKA and/or the transcription factor cAMP response element binding protein repressed leptin expression. Thereafter we determined that hCG effect could be partially blocked by pharmacologic inhibition of MAPK pathway with 50 μM PD98059 but not by the inhibition of the phosphatidylinositol 3-kinase pathway with 0.1 μm wortmannin. Moreover, hCG treatment promoted MAPK kinase and ERK1/ERK2 phosphorylation in placental cells. Finally, cotransfection with a dominant-negative mutant of MAPK blocked the hCG-mediated activation of leptin expression. In conclusion, we provide some evidence suggesting that hCG induces leptin expression in trophoblastic cells probably involving the MAPK signal transduction pathway. Copyright © 2009. Fil:Maymó, J.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Calvo, J.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Varone, C.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00137227_v150_n1_p304_Maymo
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	2 (2 amino 3 methoxyphenyl)chromone binding protein chorionic gonadotropin cyclic AMP cyclic AMP dependent protein kinase leptin luciferase mitogen activated protein kinase mitogen activated protein kinase 1 mitogen activated protein kinase 3 phosphatidylinositol 3 kinase recombinant chorionic gonadotropin wortmannin article cancer cell culture catalysis cell line cell stimulation choriocarcinoma DNA responsive element enzyme subunit explant genetic transfection hormonal regulation hormone response human human cell plasmid priority journal promoter region protein analysis protein expression protein phosphorylation reporter gene signal transduction trophoblast Western blotting
spellingShingle	2 (2 amino 3 methoxyphenyl)chromone binding protein chorionic gonadotropin cyclic AMP cyclic AMP dependent protein kinase leptin luciferase mitogen activated protein kinase mitogen activated protein kinase 1 mitogen activated protein kinase 3 phosphatidylinositol 3 kinase recombinant chorionic gonadotropin wortmannin article cancer cell culture catalysis cell line cell stimulation choriocarcinoma DNA responsive element enzyme subunit explant genetic transfection hormonal regulation hormone response human human cell plasmid priority journal promoter region protein analysis protein expression protein phosphorylation reporter gene signal transduction trophoblast Western blotting Maymó, J.L. Pérez, A.P. Sánchez-Margalet, V. Dueñas, J.L. Calvo, J.C. Varone, C.L. Up-Regulation of placental leptin by human chorionic gonadotropin
topic_facet	2 (2 amino 3 methoxyphenyl)chromone binding protein chorionic gonadotropin cyclic AMP cyclic AMP dependent protein kinase leptin luciferase mitogen activated protein kinase mitogen activated protein kinase 1 mitogen activated protein kinase 3 phosphatidylinositol 3 kinase recombinant chorionic gonadotropin wortmannin article cancer cell culture catalysis cell line cell stimulation choriocarcinoma DNA responsive element enzyme subunit explant genetic transfection hormonal regulation hormone response human human cell plasmid priority journal promoter region protein analysis protein expression protein phosphorylation reporter gene signal transduction trophoblast Western blotting
description	Leptin, the 16,000 molecular weight protein product of the obese gene, was originally considered as an adipocyte-derived signaling moleculeforthe central control of metabolism. However, leptin has been suggested to be involved in other functions during pregnancy, particularly in placenta, in which it was found to be expressed. In the present work, we have found that recombinant human chorionic gonadotropin (hCG) added to BeWo choriocarcinoma cell line showed a stimulatory effect on endogenous leptin expression, when analyzed by Western blot. This effect was time and dose dependent. Maximal effect was achieved at hCG 100 IU/ml. Moreover, hCG treatment enhanced leptin promoter activity up to 12.9 times, evaluated by transient transfection with a plasmid construction containing different promoter regions and the reporter gene luciferase. This effect was dose dependent and evidenced with all the promoter regions analyzed, regardless of length. Similar results were obtained with placental explants, thus indicating physiological relevance. Because hCG signal transduction usually involves cAMP signaling, this pathway was analyzed. Contrarily, we found that dibutyryl cAMP counteracted hCG effect on leptin expression. Furthermore, cotransfection with the catalytic subunit of PKA and/or the transcription factor cAMP response element binding protein repressed leptin expression. Thereafter we determined that hCG effect could be partially blocked by pharmacologic inhibition of MAPK pathway with 50 μM PD98059 but not by the inhibition of the phosphatidylinositol 3-kinase pathway with 0.1 μm wortmannin. Moreover, hCG treatment promoted MAPK kinase and ERK1/ERK2 phosphorylation in placental cells. Finally, cotransfection with a dominant-negative mutant of MAPK blocked the hCG-mediated activation of leptin expression. In conclusion, we provide some evidence suggesting that hCG induces leptin expression in trophoblastic cells probably involving the MAPK signal transduction pathway. Copyright © 2009.
format	JOUR
author	Maymó, J.L. Pérez, A.P. Sánchez-Margalet, V. Dueñas, J.L. Calvo, J.C. Varone, C.L.
author_facet	Maymó, J.L. Pérez, A.P. Sánchez-Margalet, V. Dueñas, J.L. Calvo, J.C. Varone, C.L.
author_sort	Maymó, J.L.
title	Up-Regulation of placental leptin by human chorionic gonadotropin
title_short	Up-Regulation of placental leptin by human chorionic gonadotropin
title_full	Up-Regulation of placental leptin by human chorionic gonadotropin
title_fullStr	Up-Regulation of placental leptin by human chorionic gonadotropin
title_full_unstemmed	Up-Regulation of placental leptin by human chorionic gonadotropin
title_sort	up-regulation of placental leptin by human chorionic gonadotropin
url	http://hdl.handle.net/20.500.12110/paper_00137227_v150_n1_p304_Maymo
work_keys_str_mv	AT maymojl upregulationofplacentalleptinbyhumanchorionicgonadotropin AT perezap upregulationofplacentalleptinbyhumanchorionicgonadotropin AT sanchezmargaletv upregulationofplacentalleptinbyhumanchorionicgonadotropin AT duenasjl upregulationofplacentalleptinbyhumanchorionicgonadotropin AT calvojc upregulationofplacentalleptinbyhumanchorionicgonadotropin AT varonecl upregulationofplacentalleptinbyhumanchorionicgonadotropin
_version_	1782028560789143552

Up-Regulation of placental leptin by human chorionic gonadotropin

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