Artículo

Giacomini, D.; Páez-Pereda, M.; Stalla, J.; Stalla, G.K.; Arzt, E. "Molecular interaction of BMP-4, TGF-β, and estrogens in lactotrophs: Impact on the PRL promoter" (2009) Molecular Endocrinology. 23(7):1102-1114
Artículo de Acceso Abierto. Puede ser descargado en su versión final
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

The regulatory role of estrogen, bone morphogenetic protein-4 (BMP-4), and TGF-β has a strong impact on hormone secretion, gene transcription, and cellular growth of prolactin (PRL)-producing cells. In contrast to TGF-β, BMP-4 induces the secretion of PRL in GH3 cells. Therefore, we studied the mechanism of their transcriptional regulation. Both BMP-4 and TGF-β inhibited the transcriptional activity of the estrogen receptor (ER). Estrogens had no effect on TGF-β-specific Smad protein transcriptional activity but presented a stimulatory action on the transcriptional activity of the BMP-4-specific Smads. BMP-4/estrogen cross talk was observed both on PRL hormone secretion and on the PRL promoter. This cross talk was abolished by the expression of a dominant-negative form for Smad-1 and treatment with ICI 182780 but not by point mutagenesis of the estrogen response element site within the promoter, suggesting that Smad/ER interaction might be dependent on the ER and a Smad binding element. By serial deletions of the PRL promoter, we observed that indeed a region responsive to BMP-4 is located between -2000 and -1500 bp upstream of the transcriptional start site. Chromatin immunoprecipitation confirmed Smad-4 binding to this region, and by specific mutation and gel shift assay, a Smad binding element responsible site was characterized. These results demonstrate that the different transcriptional factors involved in the Smad/ER complexes regulate their transcriptional activity in differential ways and may account for the different regulatory roles of BMP-4, TGF-β, and estrogens in PRL-producing cells. Copyright © 2009 by The Endocrine Society.

Registro:

Documento: Artículo
Título:Molecular interaction of BMP-4, TGF-β, and estrogens in lactotrophs: Impact on the PRL promoter
Autor:Giacomini, D.; Páez-Pereda, M.; Stalla, J.; Stalla, G.K.; Arzt, E.
Filiación:Laboratorio de Fisiología Y Biología Molecular, Departamento de Fisiología, Biología Molecular Y Celular, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina
Max-Planck Institute of Psychiatry, 80804 Munich, Germany
Affectis Pharmaceuticals, 82152 Martinsried, Germany
Laboratorio Fisiología Y Biología Molecular, Departamento de Fisiología, Biología Molecular Y Celular, Pabellon II, 1428 Buenos Aires, Argentina
Palabras clave:bone morphogenetic protein 4; estrogen; estrogen receptor; fulvestrant; prolactin; Smad protein; Smad1 protein; transforming growth factor beta; animal cell; article; binding site; chromatin immunoprecipitation; controlled study; estrogen responsive element; gene mutation; hormone release; mutagenesis; nonhuman; priority journal; prolactin secreting cell; protein analysis; protein binding; protein expression; protein function; protein localization; protein protein interaction; rat; Animals; Binding Sites; Bone Morphogenetic Protein 4; Cells, Cultured; Estrogens; Lactotrophs; Prolactin; Promoter Regions, Genetic; Protein Binding; Rats; Receptor Cross-Talk; Receptors, Estrogen; Smad Proteins; Transcriptional Activation; Transforming Growth Factor beta
Año:2009
Volumen:23
Número:7
Página de inicio:1102
Página de fin:1114
DOI: http://dx.doi.org/10.1210/me.2008-0425
Handle:http://hdl.handle.net/20.500.12110/paper_08888809_v23_n7_p1102_Giacomini
Título revista:Molecular Endocrinology
Título revista abreviado:Mol. Endocrinol.
ISSN:08888809
CODEN:MOENE
CAS:Smad protein, 62395-38-4; Smad1 protein, 444952-89-0; fulvestrant, 129453-61-8; prolactin, 12585-34-1, 50647-00-2, 9002-62-4; Bmp4 protein, rat; Bone Morphogenetic Protein 4; Estrogens; Prolactin, 9002-62-4; Receptors, Estrogen; Smad Proteins; Transforming Growth Factor beta
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_08888809_v23_n7_p1102_Giacomini.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08888809_v23_n7_p1102_Giacomini

Referencias:

  • Goffin, V., Bernichtein, S., Touraine, P., Kelly, P.A., Development and potential clinical uses of human prolactin receptor antagonists (2005) Endocrine Reviews, 26 (3), pp. 400-422. , DOI 10.1210/er.2004-0016
  • Bole-Feysot, C., Goffin, V., Edery, M., Binart, N., Kelly, P.A., Prolactin (PRL) and its receptor: Actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice (1998) Endocrine Reviews, 19 (3), pp. 225-268
  • Freeman, M.E., Kanyicska, B., Lerant, A., Nagy, G., Prolactin: Structure, function, and regulation of secretion (2000) Physiological Reviews, 80 (4), pp. 1523-1631
  • De Paul, A.L., Pons, P., Aoki, A., Torres, A.I., Heterogeneity of pituitary lactotrophs: Immunocytochemical identification of functional subtypes (1997) Acta Histochemica, 99 (3), pp. 277-289
  • Sasaki, F., Sano, M., Roles of the arcuate nucleus and ovary in the maturation of growth hormone, prolactin, and nongranulated cells in the mouse adenohypophysis during postnatal development: A stereological morphometric study by electron microscopy (1986) Endocrinology, 119 (4), pp. 1682-1689
  • Chen, C.L., Meites, J., Effects of estrogen and progesterone on serum and pituitary prolactin levels in ovariectomized rats (1970) Endocrinology, 86, pp. 503-505
  • Burnstein, K.L., Cidlowski, J.A., Multiple mechanisms for regulation of steroid hormone action (1993) Journal of Cellular Biochemistry, 51 (2), pp. 130-134. , DOI 10.1002/jcb.240510203
  • Waterman, M.L., Adler, S., Nelson, C., Greene, G.L., Evans, R.M., Rosenfeld, M.G., A single domain of the estrogen receptor confers deoxyribonucleic acid binding and transcriptional activation of the rat prolactin gene (1988) Molecular Endocrinology, 2 (1), pp. 14-21
  • Raymond, V., Bealieu, M., Labrie, F., Potent antidopaminergic activity of estradiol at the pituitary level on prolactin release (1978) Science, 200 (4346), pp. 1173-1175
  • Newton, C.J., Arzt, E., Stalla, G.K., Involvement of the estrogen receptor in the growth response of pituitary tumor cells to interleukin-2 (1994) Biochem Biophys Res Commun, 205, pp. 1930-1937
  • Gillam, M.P., Molitch, M.E., Lombardi, G., Colao, A., Advances in the treatment of prolactinomas (2006) Endocrine Reviews, 27 (5), pp. 485-534. , http://edrv.endojournals.org/cgi/reprint/27/5/485.pdf, DOI 10.1210/er.2005-9998
  • Garcia, M.M., Kapcala, L.P., Growth of a microprolactinoma to a macroprolactinoma during estrogen therapy (1995) J Endocrinol Invest, 18, pp. 450-455
  • Heaney, A.P., Horwitz, G.A., Wang, Z., Singson, R., Melmed, S., Early involvement of estrogen-induced pituitary tumor transforming gene and fibroblast growth factor expression in prolactinoma pathogenesis (1999) Nature Medicine, 5 (11), pp. 1317-1321. , DOI 10.1038/15275
  • Wiklund, J., Wertz, N., Gorski, J., A comparison of estrogen effects on uterine and pituitary growth and prolactin synthesis in F344 and Holtzman rats (1981) Endocrinology, 109 (5), pp. 1700-1707
  • Kelly, M.A., Rubinstein, M., Asa, S.L., Zhang, G., Saez, C., Bunzow, J.R., Allen, R.G., Low, M.J., Pituitary lactotroph hyperplasia and chronic hyperprolactinemia in dopamine D2 receptor-deficient mice (1997) Neuron, 19 (1), pp. 103-113. , DOI 10.1016/S0896-6273(00)80351-7
  • Asa, S.L., Kelly, M.A., Grandy, D.K., Low, M.J., Pituitary lactotroph adenomas develop after prolonged lactotroph hyperplasia in dopamine D2 receptor-deficient mice (1999) Endocrinology, 140 (11), pp. 5348-5355
  • Saiardi, A., Bozzi, Y., Baik, J.-H., Borrelli, E., Antiproliferative role of dopamine: Loss of D2 receptors causes hormonal dysfunction and pituitary hyperplasia (1997) Neuron, 19 (1), pp. 115-126. , DOI 10.1016/S0896-6273(00)80352-9
  • Sarkar, D.K., Kim, K.H., Minami, S., Transforming growth factor-β1 messenger RNA and protein expression in the pituitary gland: Its action on prolactin secretion and lactotropic growth (1992) Mol Endocrinol, 6, pp. 1825-1833
  • Delidow, B.C., Billis, W.M., Agarwal, P., White, B.A., Inhibition of prolactin gene transcription by transforming growth factor-β in GH3 cells (1991) Mol Endocrinol, 5, pp. 1716-1722
  • Lacerte, A., Lee, E.-H., Reynaud, R., Canaff, L., De Guise, C., Devost, D., Ali, S., Lebrun, J.-J., Activin inhibits pituitary prolactin expression and cell growth through Smads, Pit-1 and menin (2004) Molecular Endocrinology, 18 (6), pp. 1558-1569. , DOI 10.1210/me.2003-0470
  • Ramsdell, J.S., Transforming growth factor-α and -β are potent and effective inhibitors of GH4 pituitary tumor cell proliferation (1991) Endocrinology, 128, pp. 1981-1990
  • Coya, R., Alvarez, C.V., Perez, F., Gianzo, C., Dieguez, C., Effects of TGF-β1 on prolactin synthesis and secretion: An in-vitro study (1999) Journal of Neuroendocrinology, 11 (5), pp. 351-360. , DOI 10.1046/j.1365-2826.1999.00336.x
  • Pastorcic, M., De, A., Boyadjieva, N., Vale, W., Sarkar, D.K., Reduction in the expression and action of transforming growth factor β1 on lactotropes during estrogen-induced tumorigenesis in the anterior pituitary (1995) Cancer Res, 55, pp. 4892-4898
  • Burns, G., Sarkar, D.K., Transforming growth factor-β1-like immunoreactivity in the pituitary gland of the rat: Effect of estrogen (1993) Endocrinology, 133 (3), pp. 1444-1449. , DOI 10.1210/en.133.3.1444
  • Hentges, S., Pastorcic, M., De, A., Boyadjieva, N., Sarkar, D.K., Opposing actions of two transforming growth factor-β isoforms on pituitary lactotropic cell proliferation (2000) Endocrinology, 141 (4), pp. 1528-1535. , DOI 10.1210/en.141.4.1528
  • Scully, K.M., Rosenfeld, M.G., Pituitary development: Regulatory codes in mammalian organogenesis (2002) Science, 295 (5563), pp. 2231-2235. , DOI 10.1126/science.1062736
  • Davis, S.W., Camper, S.A., Noggin regulates Bmp4 activity during pituitary induction (2007) Developmental Biology, 305 (1), pp. 145-160. , DOI 10.1016/j.ydbio.2007.02.001, PII S0012160607000899
  • Paez-Pereda, M., Giacomini, D., Refojo, D., Nagashima, A.C., Hopfner, U., Grubler, Y., Chervin, A., Arzt, E., Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad/estrogen receptor crosstalk (2003) Proceedings of the National Academy of Sciences of the United States of America, 100 (3), pp. 1034-1039. , DOI 10.1073/pnas.0237312100
  • Day, R.N., Maurer, R.A., The distal enhancer region of the rat prolactin gene contains elements conferring response to multiple hormones (1989) Molecular Endocrinology, 3 (1), pp. 3-9
  • Kim, K.E., Day, R.N., Maurer, R.A., Functional analysis of the interaction of a tissue-specific factor with an upstream enhancer element of the rat prolactin gene (1988) Molecular Endocrinology, 2 (12), pp. 1374-1381
  • Gutierrez-Hartmann, A., Siddiqui, S., Loukin, S., Selective transcription and DNase I protection of the rat prolactin gene by GH3 pituitary cell-free extracts (1987) Proc Natl Acad Sci USA, 84, pp. 5211-5215
  • Nelson, C., Crenshaw III, E.B., Franco, R., Lira, S.A., Albert, V.R., Evans, R.M., Rosenfeld, M.G., Discrete cis-active genomic sequences dictate the pituitary cell type-specific expression of rat prolactin and growth hormone genes (1986) Nature, 322, pp. 557-562
  • Maurer, R.A., Selective binding of the estradiol receptor to a region at least one kilobase upstream from the rat prolactin gene (1985) DNA, 4 (1), pp. 1-9
  • Simmons, D.M., Voss, J.W., Ingraham, H.A., Holloway, J.M., Broide, R.S., Rosenfeld, M.G., Swanson, L.W., Pituitary cell phenotypes involve cell-specific Pit-1 mRNA translation and synergistic interactions with other classes of transcription factors (1990) Genes and Development, 4 (5), pp. 695-711
  • Day, R.N., Koike, S., Sakai, M., Muramatsu, M., Maurer, R.A., Both Pit-1 and the estrogen receptor are required for estrogen responsiveness of the rat prolactin gene (1990) Mol Endocrinol, 4, pp. 1964-1971
  • Howard, P.W., Maurer, R.A., A composite Ets/Pit-1 binding site in the prolactin gene can mediate transcriptional responses to multiple signal transduction pathways (1995) J Biol Chem, 270, pp. 20930-20936
  • Bradford, A.P., Conrad, K.E., Tran, P.H., Ostrowski, M.C., Gutierrez-Hartmann, A., GHF-1/Pit-1 functions as a cell-specific integrator of Ras signaling by targeting the Ras pathway to a composite Ets-1/GHF-1 response element (1996) Journal of Biological Chemistry, 271 (40), pp. 24639-24648. , DOI 10.1074/jbc.271.40.24639
  • Bradford, A.P., Conrad, K.E., Wasylyk, C., Wasylyk, B., Gutierrez-Hartmann, A., Functional interaction of c-Ets-1 and GHF-1/Pit-1 mediates Ras activation of pituitary-specific gene expression: Mapping of the essential c-Ets-1 domain (1995) Mol Cell Biol, 15, pp. 2849-2857
  • Diamond, S.E., Gutierrez-Hartmann, A., A 26-amino acid insertion domain defines a functional transcription switch motif in Pit-1β (1996) Journal of Biological Chemistry, 271 (46), pp. 28925-28932. , DOI 10.1074/jbc.271.46.28925
  • Bradford, A.P., Brodsky, K.S., Diamond, S.E., Kuhn, L.C., Liu, Y., Gutierrez-Hartmann, A., The Pit-1 homeodomain and β-domain interact with Ets-1 and modulate synergistic activation of the rat prolactin promoter (2000) Journal of Biological Chemistry, 275 (5), pp. 3100-3106. , DOI 10.1074/jbc.275.5.3100
  • Adamson, A.D., Friedrichsen, S., Semprini, S., Harper, C.V., Mullins, J.J., White, M.R.H., Davis, J.R.E., Human prolactin gene promoter regulation by estrogen: Convergence with tumor necrosis factor-α signaling (2008) Endocrinology, 149 (2), pp. 687-694. , http://endo.endojournals.org/cgi/reprint/149/2/687, DOI 10.1210/en.2007-1066
  • Murdoch, F.E., Byrne, L.M., Ariazi, E.A., Furlow, J.D., Meier, D.A., Gorski, J., Estrogen receptor binding to DNA: Affinity for nonpalindromic elements from the rat prolactin gene (1995) Biochemistry, 34, pp. 9144-9150
  • Berwaer, M., Monget, P., Peers, B., Mathy-Hartert, M., Bellefroid, E., Davis, J.R., Belayew, A., Martial, J.A., Multihormonal regulation of the human prolactin gene expression from 5000 bp of its upstream sequence (1991) Mol Cell Endocrinol, 80, pp. 53-64
  • Farrow, K.N., Gutierrez-Hartmann, A., Transforming growth factor-β1 inhibits rat prolactin promoter activity in GH4 neuroendocrine cells (1999) DNA Cell Biol, 18, pp. 863-873
  • Komolov, I.S., Perez-Arce, J.A., Fedotov, V.P., The effects of estradiol on prolactin and growth hormone secretion in cultured pituitary cells from intact and ovariectomized rats (1980) Endokrinologie, 75 (3), pp. 278-284
  • Miyoshi, T., Otsuka, F., Otani, H., Inagaki, K., Goto, J., Yamashita, M., Ogura, T., Makino, H., Involvement of bone morphogenetic protein-4 in GH regulation by octreotide and bromocriptine in rat pituitary GH3 cells (2008) Journal of Endocrinology, 197 (1), pp. 159-169. , DOI 10.1677/JOE-07-0549
  • Yanagisawa, J., Yanagi, Y., Masuhiro, Y., Suzawa, M., Watanabe, M., Kashiwagi, K., Toriyabe, T., Kato, S., Convergence of transforming growth factor-β and vitamin D signaling pathways on SMAD transcriptional coactivators (1999) Science, 283 (5406), pp. 1317-1321
  • Kang, H.-Y., Lin, H.-K., Hu, Y.-C., Yeh, S., Huang, K.-E., Chang, C., From transforming growth factor-β signaling to androgen action: Identification of Smad3 as an androgen receptor coregulator in prostate cancer cells (2001) Proceedings of the National Academy of Sciences of the United States of America, 98 (6), pp. 3018-3023. , DOI 10.1073/pnas.061305498
  • Hayes, S.A., Zarnegar, M., Sharma, M., Yang, F., Peehl, D.M., Ten Dijke, P., Sun, Z., SMAD3 represses androgen receptor-mediated transcription (2001) Cancer Res, 61, pp. 2112-2118
  • Song, C.-Z., Tian, X., Gelehrter, T.D., Glucocorticoid receptor inhibits transforming growth factor-β signaling by directly targeting the transcriptional activation function of Smad3 (1999) Proceedings of the National Academy of Sciences of the United States of America, 96 (21), pp. 11776-11781. , DOI 10.1073/pnas.96.21.11776
  • Giacomini, D., Paez-Pereda, M., Theodoropoulou, M., Labeur, M., Refojo, D., Gerez, J., Chervin, A., Arzt, E., Bone morphogenetic protein-4 inhibits corticotroph tumor cells: Involvement in the retinoic acid inhibitory action (2006) Endocrinology, 147 (1), pp. 247-256. , http://endo.endojournals.org/cgi/reprint/147/1/247, DOI 10.1210/en.2005-0958
  • Matsuda, T., Yamamoto, T., Muraguchi, A., Saatcioglu, F., Cross-talk between Transforming Growth Factor-β and Estrogen Receptor Signaling through Smad3 (2001) Journal of Biological Chemistry, 276 (46), pp. 42908-42914. , DOI 10.1074/jbc.M105316200
  • Yamamoto, T., Saatcioglu, F., Matsuda, T., Cross-talk between bone morphogenic proteins and estrogen receptor signaling (2002) Endocrinology, 143 (7), pp. 2635-2642. , DOI 10.1210/en.143.7.2635
  • Sarkar, D.K., Pastorcic, M., De, A., Engel, M., Moses, H., Ghasemzadeh, M.B., Role of transforming growth factor (TGF)-β type I and TGF-β type II receptors in the TGF-β1-regulated gene expression in pituitary prolactin- Secreting lactotropes (1998) Endocrinology, 139 (8), pp. 3620-3628. , DOI 10.1210/en.139.8.3620
  • Kusanagi, K., Inoue, H., Ishidou, Y., Mishima, H.K., Kawabata, M., Miyazono, K., Characterization of a bone morphogenetic protein-responsive Smad- Binding element (2000) Molecular Biology of the Cell, 11 (2), pp. 555-565
  • Massagué, J., How cells read TGF-β signals (2000) Nat Rev Mol Cell Biol, 1, pp. 169-178
  • Massagué, J., Blain, S.W., Lo, R.S., TGFβ signaling in growth control, cancer, and heritable disorders (2000) Cell, 103, pp. 295-309
  • Chen, C.-R., Kang, Y., Siegel, P.M., Massague, J., E2F4/5 and p107 as Smad cofactors linking the TGFβ receptor to c-myc repression (2002) Cell, 110 (1), pp. 19-32. , DOI 10.1016/S0092-8674(02)00801-2
  • Arzt, E., Buric, R., Stelzer, G., Stalla, J., Sauer, J., Renner, U., Stalla, G.K., Interleukin involvement in anterior pituitary cell growth regulation: Effects of IL-2 and IL-6 (1993) Endocrinology, 132 (1), pp. 459-467. , DOI 10.1210/en.132.1.459
  • Berthois, Y., Katzenellenbogen, J.A., Katzenellenbogen, B.S., Phenol red in tissue culture media is a weak estrogen: Implications concerning the study of estrogen-responsive cells in culture (1986) Proceedings of the National Academy of Sciences of the United States of America, 83 (8), pp. 2496-2500
  • Farrow, K.N., Manning, N., Schaufele, F., Gutierrez-Hartmann, A., The c-Jun δ-domain inhibits neuroendocrine promoter activity in a DNA sequence- And pituitary-specific manner (1996) Journal of Biological Chemistry, 271 (29), pp. 17139-17146. , DOI 10.1074/jbc.271.29.17139
  • Zschocke, J., Manthey, D., Bayatti, N., Van Der Burg, B., Goodenough, S., Behl, C., Estrogen receptor α-mediated silencing of caveolin gene expression in neuronal cells (2002) Journal of Biological Chemistry, 277 (41), pp. 38772-38780. , DOI 10.1074/jbc.M205664200
  • Korchynskyi, O., Ten Dijke, P., Identification and functional characterization of distinct critically important bone morphogenetic protein-specific response elements in the Id1 promoter (2002) J Biol Chem, 277, pp. 4883-4891
  • Spinella-Jaegle, S., Roman-Roman, S., Faucheu, C., Dunn, F.-W., Kawai, S., Gallea, S., Stiot, V., Rawadi, G., Opposite effects of bone morphogenetic protein-2 and transforming growth factor-β1 on osteoblast differentiation (2001) Bone, 29 (4), pp. 323-330. , DOI 10.1016/S8756-3282(01)00580-4, PII S8756328201005804
  • Norris, J.D., Fan, D., Kerner, S.A., McDonnell, D.P., Identification of a third autonomous activation domain within the human estrogen receptor (1997) Molecular Endocrinology, 11 (6), pp. 747-754. , DOI 10.1210/me.11.6.747
  • Carbia-Nagashima, A., Gerez, J., Perez-Castro, C., Paez-Pereda, M., Silberstein, S., Stalla, G.K., Holsboer, F., Arzt, E., RSUME, a Small RWD-Containing Protein, Enhances SUMO Conjugation and Stabilizes HIF-1α during Hypoxia (2007) Cell, 131 (2), pp. 309-323. , DOI 10.1016/j.cell.2007.07.044, PII S0092867407010240
  • Maurer, R.A., Notides, A.C., Identification of an estrogen-responsive element from the 5'-flanking region of the rat prolactin gene (1987) Molecular and Cellular Biology, 7 (12), pp. 4247-4254
  • Stopa, M., Anhuf, D., Terstegen, L., Gatsios, P., Gressner, A.M., Dooley, S., Participation of Smad2, Smad3, and Smad4 in transforming growth factor β (TGF-β)-induced activation of Smad7: The TGF-β response element of the promoter requires functional Smad binding element and E-box sequences for transcriptional regulation (2000) Journal of Biological Chemistry, 275 (38), pp. 29308-29317. , DOI 10.1074/jbc.M003282200
  • Li, W., Chen, F., Nagarajan, R.P., Liu, X., Chen, Y., Characterization of the DNA-binding property of Smad5 (2001) Biochemical and Biophysical Research Communications, 286 (5), pp. 1163-1169. , DOI 10.1006/bbrc.2001.5529
  • Paez-Pereda, M., Kovalovsky, D., Hopfner, U., Theodoropoulou, M., Pagotto, U., Uhl, E., Losa, M., Stalla, G.K., Retinoic acid prevents experimental Cushing syndrome (2001) Journal of Clinical Investigation, 108 (8), pp. 1123-1131. , DOI 10.1172/JCI200111098
  • Liberman, A.C., Refojo, D., Druker, J., Toscano, M., Rein, T., Holsboer, F., Arzt, E., The activated glucocorticoid receptor inhibits the transcription factor T-bet by direct protein-protein interaction (2007) FASEB Journal, 21 (4), pp. 1177-1188. , http://www.fasebj.org/cgi/reprint/21/4/1177, DOI 10.1096/fj.06-7452com

Citas:

---------- APA ----------
Giacomini, D., Páez-Pereda, M., Stalla, J., Stalla, G.K. & Arzt, E. (2009) . Molecular interaction of BMP-4, TGF-β, and estrogens in lactotrophs: Impact on the PRL promoter. Molecular Endocrinology, 23(7), 1102-1114.
http://dx.doi.org/10.1210/me.2008-0425
---------- CHICAGO ----------
Giacomini, D., Páez-Pereda, M., Stalla, J., Stalla, G.K., Arzt, E. "Molecular interaction of BMP-4, TGF-β, and estrogens in lactotrophs: Impact on the PRL promoter" . Molecular Endocrinology 23, no. 7 (2009) : 1102-1114.
http://dx.doi.org/10.1210/me.2008-0425
---------- MLA ----------
Giacomini, D., Páez-Pereda, M., Stalla, J., Stalla, G.K., Arzt, E. "Molecular interaction of BMP-4, TGF-β, and estrogens in lactotrophs: Impact on the PRL promoter" . Molecular Endocrinology, vol. 23, no. 7, 2009, pp. 1102-1114.
http://dx.doi.org/10.1210/me.2008-0425
---------- VANCOUVER ----------
Giacomini, D., Páez-Pereda, M., Stalla, J., Stalla, G.K., Arzt, E. Molecular interaction of BMP-4, TGF-β, and estrogens in lactotrophs: Impact on the PRL promoter. Mol. Endocrinol. 2009;23(7):1102-1114.
http://dx.doi.org/10.1210/me.2008-0425