Catecholestrogens are agonists of estrogen receptor dependent gene expression in MCF-7 cells
| Autor: | Rudolf Knuppen, Norbert Schütze, Günter Vollmer |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
medicine.drug_class
Endocrinology Diabetes and Metabolism Clinical Biochemistry Estrogen receptor Biology Biochemistry Endocrinology In vivo Gene expression Tumor Cells Cultured medicine Protein biosynthesis RNA Messenger skin and connective tissue diseases Receptor Molecular Biology Estrogen receptor beta Estradiol Proteins Cell Biology Molecular biology Estrogens Catechol Gene Expression Regulation Receptors Estrogen Cell culture Estrogen Protein Biosynthesis Molecular Medicine |
| Zdroj: | The Journal of Steroid Biochemistry and Molecular Biology. 48:453-461 |
| ISSN: | 0960-0760 |
| DOI: | 10.1016/0960-0760(94)90193-7 |
| Popis: | The catecholestrogens, namely 2-hydroxyestradiol (2-OH-E2) and 4-hydroxyestradiol (4-OH-E2) are important, naturally occurring metabolites of E2. Here we studied their role on estrogen dependent processes. Using the MCF-7 cell line as a model system we analyzed the potency of 2- and 4-OH-E2 on the synthesis of the 160 kDa secreted protein and on the transcription of the pS2 mRNA. Both processes are known to be E2 inducible and are mediated by the estrogen receptor. Control incubations using E2 and antiestrogens were performed to validate the assay procedure and to enable us to comparatively study the effects of the catecholestrogens. Stimulating MCF-7 cells for 2 days with 10(-8) M 2- or 4-OH-E2 resulted in an induction of the synthesis of the 160 kDa protein and in an increase in pS2 mRNA. Following hormonal stimulation with 2- or 4-OH-E2 [35S]methionine labeling of MCF-7 cells increased the level of newly synthesized and secreted 160 kDa protein 54 and 88% compared with the inductive potency of E2 (100%). The pS2 mRNA in MCF-7 cells was increased by a 2 day treatment with 10(-8) M 2- or 4-OH-E2 by 48 and 79%, respectively, compared to E2. Therefore, we conclude that the estrogen receptor is transcriptionally active in MCF-7 cells upon binding of catecholestrogens. The estrogen receptor in vivo may be active if the intracellular concentration of catecholestrogens generated is sufficient to allow occupation of the receptor. The possible action of these hormones in vivo is discussed. |
| Databáze: | OpenAIRE |
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