Androgen receptor isoforms AR-A and AR-B display functional differences in cultured human bone cells and genital skin fibroblasts
| Autor: | Ute M. Liegibel, Ulrike Hilscher, Christian Kasperk, H. U. Schweikert, Peter P. Nawroth, Angelika Bierhaus, Irma Boercsoek, U. Sommer |
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| Rok vydání: | 2003 |
| Předmět: |
Adult
Transcriptional Activation Gene isoform Clinical Biochemistry Drug Resistance Electrophoretic Mobility Shift Assay Biology Biochemistry Collagen Type I Mesoderm Transactivation Endocrinology medicine Humans Protein Isoforms Electrophoretic mobility shift assay Genitalia Fibroblast Receptor Molecular Biology Cells Cultured Skin Pharmacology Osteoblasts DNA synthesis Organic Chemistry Genetic Variation DNA Syndrome Fibroblasts Cell biology Androgen receptor medicine.anatomical_structure Receptors Androgen Androgens Female Androgen Response Element Cell Division |
| Zdroj: | Steroids. 68:1179-1187 |
| ISSN: | 0039-128X |
| DOI: | 10.1016/j.steroids.2003.08.016 |
| Popis: | Two isoforms of the androgen receptor (AR-A and AR-B), differing by a lack of the first 187 amino acids in the NH2-terminal transactivation domain of AR-A, are expressed in connective tissue and bone. Transient transfections of normal human osteoblastic cells (HOB) and of genital skin fibroblasts defective in AR (GSF-540) were utilized to compare the functional properties of AR isoforms in mesenchymal tissues. Overexpression of AR-B or AR-A did not significantly affect type I collagen secretion. However, overexpression of AR-B (but not AR-A) restored androgen-dependent DNA synthesis in AR-defective fibroblasts and increased DHT-mediated DNA synthesis three-fold in osteoblastic cells. Overexpression of AR-A did not affect DHT action but reduced DHT-dependent DNA synthesis when transfected together with AR-B. The need for an NH2-terminal sequence of the AR for complete receptor function was demonstrated using electrophoretic mobility shift assay. A peptide coding for the amino terminus of the complete AR was able to decrease the binding affinity of AR-B and increase the binding affinity of AR-A to the androgen response element. Our results suggest that AR-A lacks the ability to stimulate cell proliferation possibly due to reduced binding of AR co-activating proteins to the truncated N-terminal transactivation domain rather than due to impaired stability of the AR-A isoform. |
| Databáze: | OpenAIRE |
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