Molecular interaction of BMP-4, TGF-β, and estrogens in lactotrophs: Impact on the PRL promoter
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 mech...
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2009
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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_08888809_v23_n7_p1102_Giacomini http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_08888809_v23_n7_p1102_Giacomini_oai |
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I28-R145-paper_08888809_v23_n7_p1102_Giacomini_oai2020-10-19 Giacomini, D. Páez-Pereda, M. Stalla, J. Stalla, G.K. Arzt, E. 2009 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. Fil:Giacomini, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Páez-Pereda, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. application/pdf http://hdl.handle.net/20.500.12110/paper_08888809_v23_n7_p1102_Giacomini info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar Mol. Endocrinol. 2009;23(7):1102-1114 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 Molecular interaction of BMP-4, TGF-β, and estrogens in lactotrophs: Impact on the PRL promoter info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_08888809_v23_n7_p1102_Giacomini_oai |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-145 |
| collection |
Repositorio Digital de la Universidad de Buenos Aires (UBA) |
| topic |
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 |
| spellingShingle |
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 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 |
| topic_facet |
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 |
| description |
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. |
| format |
Artículo Artículo publishedVersion |
| author |
Giacomini, D. Páez-Pereda, M. Stalla, J. Stalla, G.K. Arzt, E. |
| author_facet |
Giacomini, D. Páez-Pereda, M. Stalla, J. Stalla, G.K. Arzt, E. |
| author_sort |
Giacomini, D. |
| title |
Molecular interaction of BMP-4, TGF-β, and estrogens in lactotrophs: Impact on the PRL promoter |
| title_short |
Molecular interaction of BMP-4, TGF-β, and estrogens in lactotrophs: Impact on the PRL promoter |
| title_full |
Molecular interaction of BMP-4, TGF-β, and estrogens in lactotrophs: Impact on the PRL promoter |
| title_fullStr |
Molecular interaction of BMP-4, TGF-β, and estrogens in lactotrophs: Impact on the PRL promoter |
| title_full_unstemmed |
Molecular interaction of BMP-4, TGF-β, and estrogens in lactotrophs: Impact on the PRL promoter |
| title_sort |
molecular interaction of bmp-4, tgf-β, and estrogens in lactotrophs: impact on the prl promoter |
| publishDate |
2009 |
| url |
http://hdl.handle.net/20.500.12110/paper_08888809_v23_n7_p1102_Giacomini http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_08888809_v23_n7_p1102_Giacomini_oai |
| work_keys_str_mv |
AT giacominid molecularinteractionofbmp4tgfbandestrogensinlactotrophsimpactontheprlpromoter AT paezperedam molecularinteractionofbmp4tgfbandestrogensinlactotrophsimpactontheprlpromoter AT stallaj molecularinteractionofbmp4tgfbandestrogensinlactotrophsimpactontheprlpromoter AT stallagk molecularinteractionofbmp4tgfbandestrogensinlactotrophsimpactontheprlpromoter AT arzte molecularinteractionofbmp4tgfbandestrogensinlactotrophsimpactontheprlpromoter |
| _version_ |
1766026715365113856 |