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Abstract:

The process of embryo implantation and trophoblast invasion is considered the most limiting factor in the establishment of pregnancy. Leptin was originally described as an adipocyte-derived signaling molecule for the central control of metabolism. However, it has been suggested that leptin is involved in other functions during pregnancy, particularly in the placenta, where it was found to be expressed. In the present work, we have found a stimulatory effect of 17beta-estradiol (E2) on endogenous leptin expression, as analyzed by Western blot, in both the BeWo choriocarcinoma cell line and normal placental explants. This effect was time and dose dependent. Maximal effect was achieved at 10 nM in BeWo cells and 1 nM in placental explants. The E 2 effects involved the estrogen receptor, as the antagonist ICI 182 780 inhibited E2-induced leptin expression. Moreover, E2 treatment enhanced leptin promoter activity up to 4-fold, as evaluated by transient transfection with a plasmid construction containing the leptin promoter region and the reporter gene luciferase. This effect was dose dependent. Deletion analysis demonstrated that a minimal promoter region between - 1951 and -1847 bp is both necessary and sufficient to achieve E2 effects. Estradiol action involved estrogen receptor 1, previously known as estrogen receptor alpha, as cotransfection with a vector encoding estrogen receptor 1 potentiated the effects of E2 on leptin expression. Moreover, E2 action probably involves membrane receptors too, as treatment with an estradiol-bovine serum albumin complex partially enhanced leptin expression. The effects of E2 could be blocked by pharmacologic inhibition of MAPK and the phosphoinositide-3-kinase (PI3K) pathways with 50 μM PD98059 and 0.1 μM Wortmannin, respectively. Moreover, cotransfection of dominant negative mutants of MAP2K or MAPK blocked E 2 induction of leptin promoter. On the other hand, E2 treatment promoted MAPK1/MAPK3 and AKT phosphorylation in placental cells. In conclusion, we provide evidence suggesting that E2 induces leptin expression in trophoblastic cells, probably through genomic and nongenomic actions via crosstalk between estrogen receptor 1 and MAPK and PI3K signal transduction pathways. © 2010 by the Society for the Study of Reproduction, Inc.

Registro:

Documento: Artículo
Título:17Beta-estradiol enhances leptin expression in human placental cells through genomic and nongenomic actions
Autor:Gambino, Y.P.; Maymó, J.L.; Pérez-Pérez, A.; Dueñas, J.L.; Sánchez-Margalet, V.; Calvo, J.C.; Varone, C.L.
Filiación:Departamento de Química Biológica, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Departamento de Bioquímica Médica Y Biología Molecular, Hospital Universitario Virgen Macarena, Universidad de Sevilla, Seville, Spain
Servicio de Ginecología Y Obstetricia, Hospital Universitario Virgen Macarena, Seville, Spain
Instituto de Biología Y Medicina Experimental (IBYME), Buenos Aires, Argentina
Palabras clave:17beta-estradiol; Gene expression; Leptin; MAPK signal transduction pathway; Placenta; 2 (2 amino 3 methoxyphenyl)chromone; estradiol; estrogen receptor; estrogen receptor alpha; fulvestrant; leptin; luciferase; mitogen activated protein kinase; phosphatidylinositol 3 kinase; wortmannin; estradiol; estrogen receptor alpha; estrogen receptor alpha, human; fulvestrant; leptin; mitogen activated protein kinase; phosphatidylinositol 3 kinase; protein kinase B; adipocyte; article; cancer cell culture; choriocarcinoma; concentration response; controlled study; embryo; enzyme inhibition; enzyme phosphorylation; explant; gene deletion; gene expression; human; human cell; human tissue; nidation; placenta; plasmid; pregnancy; priority journal; promoter region; reporter gene; signal transduction; transient transfection; trophoblast; Western blotting; analogs and derivatives; antagonists and inhibitors; female; in vitro study; metabolism; placenta; signal transduction; tumor cell line; Bovinae; Cell Line, Tumor; Estradiol; Estrogen Receptor alpha; Extracellular Signal-Regulated MAP Kinases; Female; Humans; In Vitro Techniques; Leptin; MAP Kinase Signaling System; Phosphatidylinositol 3-Kinases; Placenta; Pregnancy; Promoter Regions, Genetic; Proto-Oncogene Proteins c-akt; Receptor Cross-Talk
Año:2010
Volumen:83
Número:1
Página de inicio:42
Página de fin:51
DOI: http://dx.doi.org/10.1095/biolreprod.110.083535
Título revista:Biology of Reproduction
Título revista abreviado:Biol. Reprod.
ISSN:00063363
CODEN:BIREB
CAS:2 (2 amino 3 methoxyphenyl)chromone, 167869-21-8; estradiol, 50-28-2; fulvestrant, 129453-61-8; mitogen activated protein kinase, 142243-02-5; phosphatidylinositol 3 kinase, 115926-52-8; wortmannin, 19545-26-7; protein kinase B, 148640-14-6; Estradiol; Estrogen Receptor alpha; estrogen receptor alpha, human; Extracellular Signal-Regulated MAP Kinases; fulvestrant; Leptin; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00063363_v83_n1_p42_Gambino.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00063363_v83_n1_p42_Gambino

Referencias:

  • 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 pathologies during pregnancy (2001) Gynecologie Obstetrique Fertilite, 29 (7-8), pp. 534-537. , DOI 10.1016/S1297-9589(01)00178-3
  • Bajoria, R., Sooranna, S.R., Ward, B.S., Chatterjee, R., Prospective function of placental leptin at maternal-fetal interface (2002) Placenta, 23 (2-3), pp. 103-115. , DOI 10.1053/plac.2001.0769
  • 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 (6505), pp. 425-432. , DOI 10.1038/372425a0
  • Flier, J.S., The adipocyte: Storage depot or node on the energy information superhighway? (1995) Cell, 80, pp. 15-18
  • 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-A86
  • Ahima, R.S., Flier, J.S., (2000) Leptin. Annu Rev Physiol, 62, pp. 413-437
  • Chen, Z., Katzenellenbogen, B.S., Katzenellenbogen, J.A., Zhao, H., Directed evolution of human estrogen receptor variants with significantly enhanced androgen specificity and affinity (2004) Journal of Biological Chemistry, 279 (32), pp. 33855-33864. , DOI 10.1074/jbc.M402118200
  • Bjornstrom, L., Sjoberg, M., Mechanisms of estrogen receptor signaling: Convergence of genomic and nongenomic actions on target genes (2005) Molecular Endocrinology, 19 (4), pp. 833-842. , DOI 10.1210/me.2004-0486
  • Sasano, H., Suzuki, T., Miki, Y., Moriya, T., Intracrinology of estrogens and androgens in breast carcinoma (2008) Journal of Steroid Biochemistry and Molecular Biology, 108 (3-5), pp. 181-185. , DOI 10.1016/j.jsbmb.2007.09.012, PII S0960076007002440
  • Doria, A., Iaccarino, L., Sarzi-Puttini, P., Ghirardello, A., Zampieri, S., Arienti, S., Cutolo, M., Todesco, S., Estrogens in pregnancy and systemic lupus erythematosus (2006) Annals of the New York Academy of Sciences, 1069, pp. 247-256. , DOI 10.1196/annals.1351.022
  • Everett, R.B., MacDonald, P.C., Endocrinology of the placenta (1979) Annu Rev Med, 30, pp. 473-488
  • Genbacev, O., Joslin, R., Damsky, C.H., Polliotti, B.M., Fisher, S.J., Hypoxia alters early gestation human cytotrophoblast differentiation/ invasion in vitro and models the placental defects that occur in preeclampsia (1996) Journal of Clinical Investigation, 97 (2), pp. 540-550
  • Jiang, B., Kamat, A., Mendelson, C.R., Hypoxia prevents induction of aromatase expression in human trophoblast cells in culture: Potential inhibitory role of the hypoxia-inducible transcription factor Mash-2 (mammalian achaete-scute homologous protein-2) (2000) Mol Endocrinol, 14, pp. 1661-1673
  • Cronier, L., Guibourdenche, J., Niger, C., Malassine, A., Oestradiol stimulates morphological and functional differentiation of human villous cytotrophoblast (1999) Placenta, 20 (8), pp. 669-676. , DOI 10.1053/plac.1999.0423
  • Albrecht, E.D., Bonagura, T.W., Burleigh, D.W., Enders, A.C., Aberdeen, G.W., Pepe, G.J., Suppression of extravillous trophoblast invasion of uterine spiral arteries by estrogen during early baboon pregnancy (2006) Placenta, 27, pp. 483-490
  • Safe, S., Kim, K., Non-classical genomic estrogen receptor (ER)/specificity protein and ER/activating protein-1 signaling pathways (2008) J Mol Endocrinol, 41, pp. 263-275
  • Wade, C.B., Robinson, S., Shapiro, R.A., Dorsa, D.M., Estrogen receptor (ER)α and ERβ exhibit unique pharmacologic properties when coupled to activation of the mitogen-activated protein kinase pathway (2001) Endocrinology, 142 (6), pp. 2336-2342. , DOI 10.1210/en.142.6.2336
  • O'Neil, J.S., Burow, M.E., Green, A.E., McLachlan, J.A., Henson, M.C., Effects of estrogen on leptin gene promoter activation in MCF-7 breast cancer and JEG-3 choriocarcinoma cells: Selective regulation via estrogen receptors alpha and beta (2001) Mol Cell Endocrinol, 176, pp. 67-75
  • Stevis, P.E., Deecher, D.C., Suhadolnik, L., Mallis, L.M., Frail, D.E., Differential effects of estradiol and estradiol-BSA conjugates (1999) Endocrinology, 140, pp. 5455-5458
  • 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
  • Catalano, S., Mauro, L., Marsico, S., Giordano, C., Rizza, P., Hago, V., Montanaro, D., Ando, S., Leptin Induces, via ERK1/ERK2 Signal, Functional Activation of Estrogen Receptor α in MCF-7 Cells (2004) Journal of Biological Chemistry, 279 (19), pp. 19908-19915. , DOI 10.1074/jbc.M313191200
  • Coso, O.A., Chiariello, M., Yu, J.C., Teramoto, H., Crespo, P., Xu, N., Miki, T., Gutkind, J.S., The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway (1995) Cell, 81, pp. 1137-1146
  • Magarinos, M.P., Sanchez-Margalet, V., Kotler, M., Calvo, J.C., Varone, C.L., Leptin promotes cell proliferation and survival of trophoblastic cells (2007) Biology of Reproduction, 76 (2), pp. 203-210. , DOI 10.1095/biolreprod.106.051391
  • 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) Nature Medicine, 3 (9), pp. 1029-1033. , DOI 10.1038/nm0997-1029
  • 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 (4), pp. 378-384. , DOI 10.1053/plac.2002.0915
  • Hassink, S.G., De Lancey, E., Sheslow, D.V., Smith-Kirwin, S.M., O'Connor, D.M., Considine, R.V., Opentanova, I., Funanage, V.L., Placental leptin: An important new growth factor in intrauterine and neonatal development? (1997) Pediatrics, 100, pp. E1
  • 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) Obstetrics and Gynecology, 92 (6), pp. 1020-1028. , DOI 10.1016/S0029-7844(98)00299-3, PII S0029784498002993
  • Hardie, L., Trayhurn, P., Abramovich, D., Fowler, P., Circulating leptin in women: A longitudinal study in the menstrual cycle and during pregnancy (1997) Clinical Endocrinology, 47 (1), pp. 101-106
  • 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- 1α and 17β-oestradiol and its effect on HCG secretion (1999) Molecular Human Reproduction, 5 (11), pp. 1077-1082. , DOI 10.1093/molehr/5.11.1077
  • Maymo, J.L., Perez Perez, A., Sanchez-Margalet, V., Duenas, J.L., Calvo, J.C., Varone, C.L., Up-regulation of placental leptin by human chorionic gonadotropin (2009) Endocrinology, 150, pp. 304-313
  • Meissner, U., Ostreicher, I., Allabauer, I., Rascher, W., Dotsch, J., Synergistic effects of hypoxia and insulin are regulated by different transcriptional elements of the human leptin promoter (2003) Biochemical and Biophysical Research Communications, 303 (2), pp. 707-712. , DOI 10.1016/S0006-291X(03)00401-7
  • 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
  • Perez-Perez, A., Maymo, J., Duenas, J.L., Goberna, R., Calvo, J.C., Varone, C., Sanchez-Margalet, V., Leptin prevents apoptosis of trophoblastic cells by activation of MAPK pathway (2008) Arch Biochem Biophys, 477, pp. 390-395
  • Perez-Perez, A., Maymo, J., Gambino, Y., Duenas, J.L., Goberna, R., Varone, C., Sanchez-Margalet, V., Leptin stimulates protein synthesis-activating translation machinery in human trophoblastic cells (2009) Biol Reprod, 81, pp. 826-832
  • 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) Biology of Reproduction, 68 (2), pp. 472-477. , DOI 10.1095/biolreprod.102.006122
  • Henson, M.C., Castracane, V.D., Leptin in pregnancy (2000) Biol Reprod, 63, pp. 1219-1228
  • Lappas, M., Yee, K., Permezel, M., Rice, G.E., Release and regulation of leptin, resistin and adiponectin from human placenta, fetal membranes, and maternal adipose tissue and skeletal muscle from normal and gestational diabetes mellitus-complicated pregnancies (2005) Journal of Endocrinology, 186 (3), pp. 457-465. , DOI 10.1677/joe.1.06227
  • Ebihara, K., Ogawa, Y., Isse, N., Mori, K., Tamura, N., Masuzaki, H., Kohno, K.-I., Nakao, K., Identification of the human leptin 5'-flanking sequences involved in the trophoblast-specific transcription (1997) Biochemical and Biophysical Research Communications, 241 (3), pp. 658-663. , DOI 10.1006/bbrc.1997.7869
  • Henson, M.C., Castracane, V.D., Leptin in pregnancy: An update (2006) Biol Reprod, 74, pp. 218-229
  • Zygmunt, M., Hahn, D., Munstedt, K., Bischof, P., Lang, U., Invasion of cytotrophoblastic JEG-3 cells is stimulated by hCG in vitro (1998) Placenta, 19 (8), pp. 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
  • Bodner, J., Ebenbichler, C.F., Wolf, H.J., Muller-Holzner, E., Stanzl, U., Gander, R., Huter, O., Patsch, J.R., Leptin receptor in human term placenta: In situ hybridization and immunohistochemical localization (1999) Placenta, 20, pp. 677-682
  • Schiessl, B., Mylonas, I., Kuhn, C., Kunze, S., Schulze, S., Friese, K., Jeschke, U., Expression of estrogen receptor-alpha, estrogen receptor-beta and placental endothelial and inducible NO synthase in intrauterine growth-restricted and normal placentals (2006) Arch Med Res, 37, pp. 967-975
  • Wang, H., Zhou, L., Gupta, A., Vethanayagam, R.R., Zhang, Y., Unadkat, J.D., Mao, Q., Regulation of BCRP/ABCG2 expression by progesterone and 17beta-estradiol in human placental BeWo cells (2006) Am J Physiol Endocrinol Metab, 290, pp. E798-E807
  • Stock, S.M., Sande, E.M., Bremme, K.A., Leptin levels vary significantly during the menstrual cycle, pregnancy, and in vitro fertilization treatment: Possible relation to estradiol (1999) Fertil Steril, 72, pp. 657-662
  • Machinal, F., Dieudonne, M.N., Leneveu, M.C., Pecquery, R., Giudicelli, Y., In vivo and in vitro ob gene expression and leptin secretion in rat adipocytes: Evidence for a regional specific regulation by sex steroid hormones (1999) Endocrinology, 140, pp. 1567-1574
  • Beato, M., Herrlich, P., Schutz, G., Steroid hormone receptors: Many actors in search of a plot (1995) Cell, 83, pp. 851-857
  • Gaub, M.P., Bellard, M., Scheuer, I., Chambon, P., Sassone-Corsi, P., Activation of the ovalbumin gene by the estrogen receptor involves the fos-jun complex (1990) Cell, 63, pp. 1267-1276
  • Umayahara, Y., Kawamori, R., Watada, H., Imano, E., Iwama, N., Morishima, T., Yamasaki, Y., Kamada, T., Estrogen regulation of the insulin-like growth factor I gene transcription involves an AP-1 enhancer (1994) J Biol Chem, 269, pp. 16433-16442
  • Weisz, A., Rosales, R., Identification of an estrogen response element upstream of the human c-fos gene that binds the estrogen receptor and the AP-1 transcription factor (1990) Nucleic Acids Res, 18, pp. 5097-5106
  • O'Lone, R., Frith, M.C., Karlsson, E.K., Hansen, U., Genomic targets of nuclear estrogen receptors (2004) Mol Endocrinol, 18, pp. 1859-1875
  • Vanacker, J.M., Pettersson, K., Gustafsson, J.A., Laudet, V., Transcriptional targets shared by estrogen receptor-related receptors (ERRs) and estrogen receptor (ER) alpha, but not by ERbeta (1999) EMBO J, 18, pp. 4270-4279
  • Porter, W., Saville, B., Hoivik, D., Safe, S., Functional synergy between the transcription factor Sp1 and the estrogen receptor (1997) Mol Endocrinol, 11, pp. 1569-1580
  • Li, C., Briggs, M.R., Ahlborn, T.E., Kraemer, F.B., Liu, J., Requirement of Sp1 and estrogen receptor alpha interaction in 17beta-estradiol-mediated transcriptional activation of the low density lipoprotein receptor gene expression (2001) Endocrinology, 142, pp. 1546-1553
  • Duan, R., Porter, W., Safe, S., Estrogen-induced c-fos protooncogene expression in MCF-7 human breast cancer cells: Role of estrogen receptor Sp1 complex formation (1998) Endocrinology, 139, pp. 1981-1990
  • Castro-Rivera, E., Samudio, I., Safe, S., Estrogen regulation of cyclin D1 gene expression in ZR-75 breast cancer cells involves multiple enhancer elements (2001) J Biol Chem, 276, pp. 30853-30861
  • Safe, S., Transcriptional activation of genes by 17 beta-estradiol through estrogen receptor-Sp1 interactions (2001) Vitam Horm, 62, pp. 231-252
  • Kruger, I., Vollmer, M., Simmons, D., Elsasser, H.-P., Philipsen, S., Suske, G., Sp1/Sp3 compound heterozygous mice are not viable: Impaired erythropoiesis and severe placental defects (2007) Developmental Dynamics, 236 (8), pp. 2235-2244. , DOI 10.1002/dvdy.21222
  • Mason, M.M., He, Y., Chen, H., Quon, M.J., Reitman, M., Regulation of leptin promoter function by Sp1, C/EBP, and a novel factor (1998) Endocrinology, 139, pp. 1013-1022
  • Prossnitz, E.R., Oprea, T.I., Sklar, L.A., Arterburn, J.B., The ins and outs of GPR30: A transmembrane estrogen receptor (2008) J Steroid Biochem Mol Biol, 109, pp. 350-353
  • Kumar, P., Kamat, A., Mendelson, C.R., Estrogen receptor alpha (ERalpha) mediates stimulatory effects of estrogen on aromatase (CYP19) gene expression in human placenta (2009) Mol Endocrinol, 23, pp. 784-793
  • Bocquel, M.T., Kumar, V., Stricker, C., Chambon, P., Groenmeyer, H., The contribution of the N- And C-terminal regions of steroid receptors to activation of transcription is both receptor and cell-specific (1989) Nucleic Acids Research, 17 (7), pp. 2581-2595
  • Sadovsky, Y., Webb, P., Lopez, G., Baxter, J.D., Fitzpatrick, P.M., Gizang-Ginsberg, E., Cavailles, V., Kushner, P.J., Transcriptional activators differ in their responses to overexpression of TATA-box-binding protein (1995) Mol Cell Biol, 15, pp. 1554-1563
  • Losel, R., Wehling, M., Nongenomic actions of steroid hormones (2003) Nat Rev Mol Cell Biol, 4, pp. 46-56
  • Pedram, A., Razandi, M., Levin, E.R., Nature of functional estrogen receptors at the plasma membrane (2006) Molecular Endocrinology, 20 (9), pp. 1996-2009. , http://mend.endojournals.org/cgi/reprint/20/9/1996, DOI 10.1210/me.2005-0525
  • Razandi, M., Oh, P., Pedram, A., Schnitzer, J., Levin, E.R., ERs associate with and regulate the production of caveolin: Implications for signaling and cellular actions (2002) Molecular Endocrinology, 16 (1), pp. 100-115. , DOI 10.1210/me.16.1.100
  • Migliaccio, A., Di Domenico, M., Castoria, G., De Falco, A., Bointempo, P., Nola, E., Auricchio, F., Tyrosine kinase/p21(ras)/MAP-kinase pathway activation by estradiol-receptor complex in MCF-7 cells (1996) EMBO Journal, 15 (6), pp. 1292-1300
  • Chen, Z., Yuhanna, I.S., Galcheva-Gargova, Z., Karas, R.H., Mendelsohn, M.E., Shaul, P.W., Estrogen receptor mediates the nongenomic activation of endothelial nitric oxide synthase by estrogen (1999) Journal of Clinical Investigation, 103 (3), pp. 401-406
  • Jessop, H.L., Sjoberg, M., Cheng, M.Z., Zaman, G., Wheeler-Jones, C.P.D., Lanyon, L.E., Mechanical strain and estrogen activate estrogen receptor α in bone cells (2001) Journal of Bone and Mineral Research, 16 (6), pp. 1045-1055
  • Watters, J.J., Campbell, J.S., Cunningham, M.J., Krebs, E.G., Dorsa, D.M., Rapid membrane effects of steroids in neuroblastoma cells: Effects of estrogen on mitogen activated protein kinase signalling cascade and c-fos immediate early gene transcription (1997) Endocrinology, 138, pp. 4030-4033
  • Simoncini, T., Hafezi-Moghadam, A., Brazil, D.P., Ley, K., Chin, W.W., Liao, J.K., Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase (2000) Nature, 407, pp. 538-541
  • Castoria, G., Migliaccio, A., Bilancio, A., Di Domenico, M., De Falco, A., Lombardi, M., Fiorentino, R., Auricchio, F., PI3-kinase in concert with Src promotes the S-phase entry of oestradiol-stimulated MCF-7 cells (2001) EMBO Journal, 20 (21), pp. 6050-6059. , DOI 10.1093/emboj/20.21.6050
  • Marino, M., Acconcia, F., Bresciani, F., Weisz, A., Trentalance, A., Distinct nongenomic signal transduction pathways controlled by 17beta-estradiol regulate DNA synthesis and cyclin D(1) gene transcription in HepG2 cells (2002) Mol Biol Cell, 13, pp. 3720-3729

Citas:

---------- APA ----------
Gambino, Y.P., Maymó, J.L., Pérez-Pérez, A., Dueñas, J.L., Sánchez-Margalet, V., Calvo, J.C. & Varone, C.L. (2010) . 17Beta-estradiol enhances leptin expression in human placental cells through genomic and nongenomic actions. Biology of Reproduction, 83(1), 42-51.
http://dx.doi.org/10.1095/biolreprod.110.083535
---------- CHICAGO ----------
Gambino, Y.P., Maymó, J.L., Pérez-Pérez, A., Dueñas, J.L., Sánchez-Margalet, V., Calvo, J.C., et al. "17Beta-estradiol enhances leptin expression in human placental cells through genomic and nongenomic actions" . Biology of Reproduction 83, no. 1 (2010) : 42-51.
http://dx.doi.org/10.1095/biolreprod.110.083535
---------- MLA ----------
Gambino, Y.P., Maymó, J.L., Pérez-Pérez, A., Dueñas, J.L., Sánchez-Margalet, V., Calvo, J.C., et al. "17Beta-estradiol enhances leptin expression in human placental cells through genomic and nongenomic actions" . Biology of Reproduction, vol. 83, no. 1, 2010, pp. 42-51.
http://dx.doi.org/10.1095/biolreprod.110.083535
---------- VANCOUVER ----------
Gambino, Y.P., Maymó, J.L., Pérez-Pérez, A., Dueñas, J.L., Sánchez-Margalet, V., Calvo, J.C., et al. 17Beta-estradiol enhances leptin expression in human placental cells through genomic and nongenomic actions. Biol. Reprod. 2010;83(1):42-51.
http://dx.doi.org/10.1095/biolreprod.110.083535