Androgen Receptor Activation Integrates Complex Transcriptional Effects in Osteoblasts, Involving the Growth Factors TGF-β and IGF-I, and Transcription Factor C/EBPδ

The study demonstrated that dihydrotestosterone (DHT) suppressed IGF-I gene promoter activity in prostaglandin E2 (PGE2) induced osteoblasts through a C/EBP response element in exon 1 of the igf1 gene. This suppression required a functional androgen receptor (AR) and was independent of upstream Smad and Runx response elements. DHT also inhibited TGF-β induced IGF-I promoter activity but did not affect TGF-β's influence on DNA or collagen synthesis. Additionally, DHT differentially regulated other TGF-β activities, such as enhancing Smad dependent gene promoter activity. These findings highlighted the complex interactions between DHT and bone growth regulators, suggesting potential complications from anabolic steroid use in DHT sensitive tissues.