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Abstract:

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.

Registro:

Documento: Artículo
Título:Up-Regulation of placental leptin by human chorionic gonadotropin
Autor:Maymó, J.L.; Pérez, A.P.; Sánchez-Margalet, V.; Dueñas, J.L.; Calvo, J.C.; Varone, C.L.
Filiación:Departamento de Química Biológica, 1428 Buenos Aires, Argentina
Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Instituto de Biología y Medicina Experimental, 1428 Buenos Aires, Argentina
Departamento de Bioquímica Médica y Biología Molecular, Spain
Facultad de Medicina, Universidad de Sevilla, Servicio de Ginecología y Obstetricia, Hospital Universitario Virgen Macarena, 41009 Sevilla, Spain
Departamento de Química Biológica, Ciudad Universitaria Pabellon 2 piso 4, 1428 Buenos Aires, Argentina
Palabras clave: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
Año:2009
Volumen:150
Número:1
Página de inicio:304
Página de fin:313
DOI: http://dx.doi.org/10.1210/en.2008-0522
Título revista:Endocrinology
Título revista abreviado:Endocrinology
ISSN:00137227
CODEN:ENDOA
CAS:2 (2 amino 3 methoxyphenyl)chromone, 167869-21-8; chorionic gonadotropin, 9002-61-3; cyclic AMP, 60-92-4; cyclic AMP dependent protein kinase; mitogen activated protein kinase, 142243-02-5; mitogen activated protein kinase 1, 137632-08-7; mitogen activated protein kinase 3, 137632-07-6; phosphatidylinositol 3 kinase, 115926-52-8; recombinant chorionic gonadotropin, 177073-44-8; wortmannin, 19545-26-7
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00137227_v150_n1_p304_Maymo.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00137227_v150_n1_p304_Maymo

Referencias:

  • Cervero, A., Horcajadas, J.A., Martin, J., Pellicer, A., Simon, C., The leptin system during human endometrial receptivity and preimplantation development (2004) J Clin Endocrinol Metab, 89, pp. 2442-2451
  • Kauma, S.W., Cytokines in implantation (2000) J Reprod Fertil, (SUPPL. 55), pp. 31-42
  • Fitzgerald, J.S., Busch, S., Wengenmayer, T., Foerster, K., de la Motte, T., Poehlmann, T.G., Markert, U.R., Signal transduction in trophoblast invasion (2005) Chem Immunol Allergy, 88, pp. 181-199
  • Castellucci, M., De Matteis, R., Meisser, A., Cancello, R., Monsurro, V., Islami, D., Sarzani, R., Bischof, P., Leptin modulates extracellular matrix molecules and metalloproteinases: Possible implications for trophoblast invasion (2000) Mol Hum Reprod, 6, pp. 951-958
  • Hauguel-de Mouzon, S., Lepercq, J., Placental leptin and pregnancy pathologies] (2001) Gynecol Obstet Fertil, 29, pp. 534-537
  • Bajoria, R., Sooranna, S.R., Ward, B.S., Chatterjee, R., Prospective function of placental leptin at maternal-fetal interface (2002) Placenta, 23, pp. 103-115
  • Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., Friedman, J.M., Positional cloning of the mouse obese gene and its human homologue (1994) Nature, 372, pp. 425-432
  • Flier, J.S., The adipocyte: Storage depot or node on the energy information superhighway? (1995) Cell, 80, pp. 15-18
  • Ahima, R.S., Flier, J.S., Leptin (2000) Annu Rev Physiol, 62, pp. 413-437
  • Sagawa, N., Yura, S., Itoh, H., Mise, H., Kakui, K., Korita, D., Takemura, M., Fujii, S., Role of leptin in pregnancy-a review (2002) Placenta, 23 (SUPPL. A), pp. S80-S86
  • Reitman, M.L., Bi, S., Marcus-Samuels, B., Gavrilova, O., Leptin and its role in pregnancy and fetal development-an overview (2001) Biochem Soc Trans, 29, pp. 68-72
  • Cervero, A., Horcajadas, J.A., Dominguez, F., Pellicer, A., Simon, C., Leptin system in embryo development and implantation: A protein in search of a function (2005) Reprod Biomed Online, 10, pp. 217-223
  • Henson, M.C., Castracane, V.D., Leptin in pregnancy: An update (2006) Biol Reprod, 74, pp. 218-229
  • Rao, C.V., An overview of the past, present, and future of nongonadal LH/hCG actions in reproductive biology and medicine (2001) Semin Reprod Med, 19, pp. 7-17
  • Dufau, M.L., The luteinizing hormone receptor (1998) Annu Rev Physiol, 60, pp. 461-496
  • Filicori, M., Fazleabas, A.T., Huhtaniemi, I., Licht, P., Rao, C.V., Tesarik, J., Zygmunt, M., Novel concepts of human chorionic gonadotropin: Reproductive system interactions and potential in the management of infertility (2005) Fertil Steril, 84, pp. 275-284
  • Boelhauve, M., Sinowatz, F., WolfE, Paula-Lopes, F.F., Maturation of bovine oocytes in the presence of leptin improves development and reduces apoptosis of in vitro-produced blastocysts (2005) Biol Reprod, 73, pp. 737-744
  • Ryu, K.S., Gilchrist, R.L., Koo, Y.B., Ji, I., Ji, T.H., Gene, interaction, signal generation, signal divergence and signal transduction of the LH/CG receptor (1998) Int J Gynaecol Obstet, 60 (SUPPL. 1), pp. S9-S20
  • Magarinos, M.P., Sanchez-Margalet, V., Kotler, M., Calvo, J.C., Varone, C.L., Leptin promotes cell proliferation and survival of trophoblastic cells (2007) Biol Reprod, 76, pp. 203-210
  • Pidoux, G., Gerbaud, P., Tsatsaris, V., Marpeau, O., Ferreira, F., Meduri, G., Guibourdenche, J., Frendo, J.L., Biochemical characterization and modulation of LH/CG-receptor during human trophoblast differentiation (2007) J Cell Physiol, 212, pp. 26-35
  • Bradford, M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding (1976) Anal Biochem, 72, pp. 248-254
  • Bi, S., Gavrilova, O., Gong, D.W., Mason, M.M., Reitman, M., Identification of a placental enhancer for the human leptin gene (1997) J Biol Chem, 272, pp. 30583-30588
  • Mellon, P.L., Clegg, C.H., Correll, L.A., McKnight, G.S., Regulation of transcription by cyclic AMP-dependent protein kinase (1989) Proc Natl Acad Sci USA, 86, pp. 4887-4891
  • Gonzalez, G.A., Montminy, M.R., Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133 (1989) Cell, 59, pp. 675-680
  • Coso, O.A., Chiariello, M., Yu, J.C., Teramoto, H., Crespo, P., Xu, N., Miki, T., Gutkind, J.S., The small GTP-binding proteins Rac l and Cdc42 regulate the activity of the JNK/SAPK signaling pathway (1995) Cell, 81, pp. 1137-1146
  • Masuzaki, H., Ogawa, Y., Sagawa, N., Hosoda, K., Matsumoto, T., Mise, H., Nishimura, H., Nakao, K., Nonadipose tissue production of leptin: Leptin as a novel placenta-derived hormone in humans (1997) Nat Med, 3, pp. 1029-1033
  • Cauzac, M., Czuba, D., Girard, J., Hauguel-de Mouzon, S., Transduction of leptin growth signals in placental cells is independent of JAK-STAT activation (2003) Placenta, 24, pp. 378-384
  • Conti, M., Harwood, J.P., Hsueh, A.J., Dufau, M.L., Catt, K.J., Gonadotropininduced loss of hormone receptors and desensitization of adenylate cyclase in the ovary (1976) J Biol Chem, 251, pp. 7729-7731
  • Segaloff, D.L., Ascoli, M., The lutropin/choriogonadotropin receptor. 4 years later (1993) Endocr Rev, 14, pp. 324-347
  • Cameo, P., Srisuparp, S., Strakova, Z., Fazleabas, A.T., Chorionic gonadotropin and uterine dialogue in the primate (2004) Reprod Biol Endocrinol, 2, p. 50
  • Faure, M., Voyno-Yasenetskaya, T.A., Bourne, H.R., cAMP and βγ subunits of heterotrimeric G proteins stimulate the mitogen-activated protein kinase pathway in COS-7 cells (1994) J Biol Chem, 269, pp. 7851-7854
  • Cameron, M.R., Foster, J.S., Bukovsky, A., Wimalasena, J., Activation of mitogen-activated protein kinases by gonadotropins and cyclic adenosine 5'- monophosphates in porcine granulosa cells (1996) Biol Reprod, 55, pp. 111-119
  • Hardie, L., Trayhurn, P., Abramovich, D., Fowler, P., Circulating leptin in women: A longitudinal study in the menstrual cycle and during pregnancy (1997) Clin Endocrinol (Oxf), 47, pp. 101-106
  • Henson, M.C., Swan, K.F., O'Neil, J.S., Expression of placental leptin and leptin receptor transcripts in early pregnancy and at term (1998) Obstet Gynecol, 92, pp. 1020-1028
  • Iwagaki, S., Yokoyama, Y., Tang, L., Takahashi, Y., Nakagawa, Y., Tamaya, T., Augmentation of leptin and hypoxia-inducible factor lα mRNAs in the preeclamptic placenta (2004) Gynecol Endocrinol, 18, pp. 263-268
  • Zygmunt M, Hahm D, Munstedt K, Bischof P. Lang U 1998 Invasion of cytotrophoblastic JEG-3 cells is stimulated by hCG in vitro. Placenta 19:587-593; Standley, P.R., Standley, C.A., Identification of a functional Na + /Mg2 + exchanger in human trophoblast cells (2002) Am J Hypertens, 15, pp. 565-570
  • Rebut-Bonneton, C., Segond, N., Demignon, J., Porquet, D., Evain-Brion, D., Effects of calcitonin on human trophoblastic cells in culture: Absence of autocrine control (1992) Mol Cell Endocrinol, 85, pp. 65-71
  • Monjo, M., Pujol, E., Roca, P., α2- to β3-Adrenoceptor switch in 3T3-L1 preadipocytes and adipocytes: Modulation by testosterone, 17β-estradiol, and progesterone (2005) Am J Physiol Endocrinol Metab, 289, pp. E145-E150
  • Popovic, V., Casanueva, F.F., Leptin, nutrition and reproduction: New insights (2002) Hormones (Athens), 1, pp. 204-217
  • Coya, R., Gualillo, O., Pineda, J., Garcia, M.C., Busturia, M.A., Aniel-Quiroga, A., Martul, P., Senaris, R.M., Effect of cyclic 3',5'-adenosine monophosphate, glucocorticoids, and insulin on leptin messenger RNA levels and leptin secretion in cultured human trophoblast (2001) Biol Reprod, 65, pp. 814-819
  • Ambrosini, G., Nath, A.K., Sierra-Honigmann, M.R., Flores-Riveros, J., Transcriptional activation of the human leptin gene in response to hypoxia. Involvement of hypoxia-inducible factor 1 (2002) J Biol Chem, 277, pp. 34601-34609
  • Islami, D., Chardonnens, D., Campana, A., Bischof, P., Comparison of the effects of GnRH-I and GnRH-II on HCG synthesis and secretion by first trimester trophoblast (2001) Mol Hum Reprod, 7, pp. 3-9
  • Islami, D., Bischof, P., Chardonnens, D., Possible interactions between leptin, gonadotrophin-releasing hormone (GnRH-I and II) and human chorionic gonadotrophin (hCG) (2003) Eur J Obstet Gynecol Reprod Biol, 110, pp. 169-175
  • Cameo, P., Bischof, P., Calvo, J.C., Effect of leptin on progesterone, human chorionic gonadotropin, and interleukin-6 secretion by human term trophoblast cells in culture (2003) Biol Reprod, 68, pp. 472-477
  • Chardonnens, D., Cameo, P., Aubert, M.L., Pralong, F.P., Islami, D., Campana, A., Gaillard, R.C., Bischof, P., Modulation of human cytotrophoblastic leptin secretion by interleukin-lα and 17β-oestradiol and its effect on HCG secretion (1999) Mol Hum Reprod, 5, pp. 1077-1082
  • Coya, R., Martul, P., Algorta, J., Aniel-Quiroga, M.A., Busturia, M.A., Senaris, R., Effect of leptin on the regulation of placental hormone secretion in cultured human placental cells (2006) Gynecol Endocrinol, 22, pp. 620-626
  • Islami, D., Bischof, P., Chardonnens, D., Modulation of placental vascular endothelial growth factor by leptin and hCG (2003) Mol Hum Reprod, 9, pp. 395-398
  • Mason, M.M., He, Y., Chen, H., Quon, M.J., Reitman, M., Regulation of leptin promoter function by Spl, C/EBP, and a novel factor (1998) Endocrinology, 139, pp. 1013-1022
  • Sirois, J., Richards, J.S., Transcriptional regulation of the rat prostaglandin endoperoxide synthase 2 gene in granulosa cells. Evidence for the role of a cis-acting C/EBP β promoter element (1993) J Biol Chem, 268, pp. 21931-21938
  • Nalbant, D., Williams, S.C., Stocco, D.M., Khan, S.A., Luteinizing hormonedependent gene regulation in Leydig cells may be mediated by CCAAT/enhancer-binding protein-β (1998) Endocrinology, 139, pp. 272-279
  • Dos Santos, E., Dieudonne, M.N., Leneveu, M.C., Pecquery, R., Serazin, V., Giudicelli, Y., In vitro effects of chorionic gonadotropin hormone on human adipose development (2007) J Endocrinol, 194, pp. 313-325
  • Slieker LJ, Sloop KW, Surface PL, Kriauciunas A, LaQuier F, Manetta J, Bue-Valleskey J, Stephens TW 1996 Regulation of expression of ob mRNA and protein by glucocorticoids and cAMP. J Biol Chem 271:5301-5304; Zhao, J., Kunz, T.H., Tumba, N., Schulz, L.C., Li, C., Reeves, M., Widmaier, E.P., Comparative analysis of expression and secretion of placental leptin in mammals (2003) Am J Physiol Regul Integr Comp Physiol, 285, pp. R438-R446
  • Menon, K.M., Munshi, U.M., Clouser, C.L., Nair, A.K., Regulation of luteinizing hormone/human chorionic gonadotropin receptor expression: A perspective (2004) Biol Reprod, 70, pp. 861-866
  • Salvador, L.M., Maizels, E., Hales, D.B., Miyamoto, E., Yamamoto, H., Hunzicker-Dunn, M., Acute signaling by the LH receptor is independent of protein kinase C activation (2002) Endocrinology, 143, pp. 2986-2994
  • Srisuparp, S., Strakova, Z., Brudney, A., Mukherjee, S., Reierstad, S., Hunzicker-Dunn, M., Fazleabas, A.T., Signal transduction pathways activated by chorionic gonadotropin in the primate endometrial epithelial cells (2003) Biol Reprod, 68, pp. 457-464
  • Carvalho, C.R., Carvalheira, J.B., Lima, M.H., Zimmerman, S.F., Caperuto, L.C., Amanso, A., Gasparetti, A.L., Saad, M.J., Novel signal transduction pathway for luteinizing hormone and its interaction with insulin: Activation of Janus kinase/signal transducer and activator of transcription and phosphoinositol 3-kinase/Akt pathways (2003) Endocrinology, 144, pp. 638-647
  • Amsterdam, A., Hanoch, T., Dantes, A., Tajima, K., Strauss, J.F., Seger, R., Mechanisms of gonadotropin desensitization (2002) Mol Cell Endocrinol, 187, pp. 69-74

Citas:

---------- APA ----------
Maymó, J.L., Pérez, A.P., Sánchez-Margalet, V., Dueñas, J.L., Calvo, J.C. & Varone, C.L. (2009) . Up-Regulation of placental leptin by human chorionic gonadotropin. Endocrinology, 150(1), 304-313.
http://dx.doi.org/10.1210/en.2008-0522
---------- CHICAGO ----------
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" . Endocrinology 150, no. 1 (2009) : 304-313.
http://dx.doi.org/10.1210/en.2008-0522
---------- MLA ----------
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" . Endocrinology, vol. 150, no. 1, 2009, pp. 304-313.
http://dx.doi.org/10.1210/en.2008-0522
---------- VANCOUVER ----------
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. Endocrinology. 2009;150(1):304-313.
http://dx.doi.org/10.1210/en.2008-0522