Requirement of Estrogen Receptor-α in Insulin-like Growth Factor-1 (IGF-1)-induced Uterine Responses and in Vivo Evidence for IGF-1/Estrogen Receptor Cross-talk
| Autor: | Jonathan Lindzey, Michele Raviscioni, Richard P. DiAugustine, Julie F. Foley, Paolo Ciana, Diane M. Klotz, Kenneth S. Korach, Sylvia C. Hewitt, Adriana Maggi |
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| Rok vydání: | 2002 |
| Předmět: |
Time Factors
Transcription Genetic medicine.medical_treatment Estrogen receptor Biochemistry Mice Phosphatidylinositol 3-Kinases Insulin-like growth factor Insulin-Like Growth Factor I Luciferases Promoter Regions Genetic Fulvestrant Mice Knockout Estradiol biology Estrogen Antagonists Immunohistochemistry Receptors Estrogen Female Signal transduction Cell Division Protein Binding Signal Transduction medicine.medical_specialty medicine.drug_class Immunoblotting Alpha (ethology) Mice Transgenic Protein Serine-Threonine Kinases Response Elements Models Biological Proto-Oncogene Proteins Internal medicine medicine Animals Molecular Biology Estrogen receptor beta Cell Nucleus Uterus Estrogen Receptor alpha Cell Biology Precipitin Tests Enzyme Activation Insulin receptor Endocrinology Bromodeoxyuridine Estrogen biology.protein Proto-Oncogene Proteins c-akt Estrogen receptor alpha |
| Zdroj: | Journal of Biological Chemistry. 277:8531-8537 |
| ISSN: | 0021-9258 |
| Popis: | In the uterus insulin-like growth factor-1 (IGF-1) signaling can be initiated by estradiol acting through its nuclear receptor (estrogen receptor (ER)) to stimulate the local synthesis of IGF-1. Conversely, in vitro studies have demonstrated that estradiol-independent ER transcriptional activity can be induced by IGF-1 signaling, providing evidence for a cross-talk mechanism between IGF-1 and ER. To investigate whether ER alpha is required for uterine responses to IGF-1 in vivo, both wild-type (WT) and ER alpha knockout (alpha ERKO) mice were administered IGF-1, and various uterine responses to IGF-1 were compared. In both WT and alpha ERKO mice, IGF-1 treatment resulted in phosphorylation of uterine IGF-1 receptor (IGF-1R) and formation of an IGF-1R/insulin receptor substrate-1/ phosphatidylinositol 3-kinase signaling complex. In addition, IGF-1 stimulated phosphorylation of uterine Akt and MAPK in both WT and alpha ERKO mice. However, IGF-1 treatment stimulated BrdUrd incorporation and proliferating cell nuclear antigen expression in WT uteri only. To determine whether ER alpha can be activated in vivo by IGF-1 signaling, transgenic mice carrying a luciferase gene driven by two estrogen response elements (ERE-luciferase mice) were utilized. Treatment of ovariectomized ERE-luciferase mice with IGF-1 resulted in an increase in uterine luciferase activity that was attenuated in the presence of the ER antagonist ICI 182,780. Together these data demonstrate that 1) functional signaling proximal to IGF-1R is maintained in the alpha ERKO mouse uterus, 2) ER alpha is necessary for IGF-1 induction of uterine nuclear proliferative responses, and 3) cross-talk between IGF-1R and ER signaling pathways exists in vivo. |
| Databáze: | OpenAIRE |
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