Regulation of osteoprotegerin production by androgens and anti-androgens in human osteoblastic lineage cells

Abstract

5Alpha-dihydrotestosterone (DHT) dose-dependently decreased OPG mRNA levels and protein concentrations in hFOB/AR-6 cells by up to 50 and 60% respectively (P<0.001). Inhibition of OPG mRNA levels and protein production by 5alpha-DHT was completely abrogated by the AR antagonist, hydroxyflutamide (OHF), indicating that these effects are directly mediated by the AR. Of note, OHF alone increased OPG mRNA levels and protein secretion by 2- to 3-fold. Moreover, 5alpha-DHT and testosterone also decreased OPG protein secretion by 40-46% in the untransformed MSC cells, while OHF stimulated it. In conclusion, we demonstrate that androgens specifically inhibit OPG mRNA levels and protein secretion by osteoblastic cells.