Nongenotropic, Sex-Nonspecific Signaling through the Estrogen or Androgen Receptors
| Autor: | Teresita Bellido, Donald L. Bodenner, Robert L. Jilka, K. Han, G. B. DiGregorio, Paula K. Roberson, Charles A. O'Brien, John A. Katzenellenbogen, Benita S. Katzenellenbogen, Stavros C. Manolagas, Stavroula Kousteni, Lilian I. Plotkin, Li Han, Robert S. Weinstein |
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| Rok vydání: | 2001 |
| Předmět: |
0303 health sciences
medicine.medical_specialty Biochemistry Genetics and Molecular Biology(all) medicine.drug_class Biology Androgen General Biochemistry Genetics and Molecular Biology Cell biology Androgen receptor 03 medical and health sciences 0302 clinical medicine Endocrinology Sex steroid Estrogen 030220 oncology & carcinogenesis Internal medicine medicine Receptor Estrogen receptor alpha Estrogen receptor beta 030304 developmental biology Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Cell. 104:719-730 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/s0092-8674(01)00268-9 |
| Popis: | The relationship of the classical receptors and their transcriptional activity to nongenotropic effects of steroid hormones is unknown. We demonstrate herein a novel paradigm of sex steroid action on osteoblasts, osteocytes, embryonic fibroblasts, and HeLa cells involving activation of a Src/Shc/ERK signaling pathway and attenuating apoptosis. This action is mediated by the ligand binding domain and eliminated by nuclear targeting of the receptor protein; ERα, ERβ, or AR can transmit it with similar efficiency irrespective of whether the ligand is an estrogen or an androgen. This antiapoptotic action can be dissociated from the transcriptional activity of the receptor with synthetic ligands, providing proof of principle for the development of function-specific—as opposed to tissue-selective—and gender-neutral pharmacotherapeutics. |
| Databáze: | OpenAIRE |
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