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Androgen receptor isoforms AR-A and AR-B display functional differences in cultured human bone cells and genital skin fibroblasts

Two isoforms of the androgen receptor (AR-A and AR-B), differing by a lack of the first 187 amino acids in the NH 2-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 d...

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Bibliographic Details
Published in:Steroids 2003-12, Vol.68 (14), p.1179-1187
Main Authors: Liegibel, Ute M., Sommer, Ulrike, Boercsoek, Irma, Hilscher, Ulrike, Bierhaus, Angelika, Schweikert, Hans Udo, Nawroth, Peter, Kasperk, Christian
Format: Article
Language:English
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Summary:Two isoforms of the androgen receptor (AR-A and AR-B), differing by a lack of the first 187 amino acids in the NH 2-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 NH 2-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.
ISSN:0039-128X
1878-5867
DOI:10.1016/j.steroids.2003.08.016