Testosterone inhibits osteoclast formation stimulated by parathyroid hormone through androgen receptor

Androgens play an important role in the regulation of bone metabolism in an imals and humans. The present study was performed to investigate whether an drogens would affect osteoclast formation stimulated by parathyroid hormone (PTH) in mouse bone cell cultures and its mechanism. Testosterone as well as alpha -dihydrotestosterone (DHT) concentration-dependently inhibited ost eoclast formation induced by PTH-(1-34). 10(-8) M ICI 182780, an estrogen r eceptor inhibitor, did not affect PTH-induced osteoclast formation antagoni zed by 10-8 M testosterone, although it completely antagonized the effects of 10-8 M 17 beta -estradiol, Moreover, 3 muM 4-androsten-4-ol-3, 17-dione, an aromatase inhibitor, did not affect PTH-induced osteoclast formation an tagonized by testosterone, Hydroxyflutamide, an androgen receptor antagonis t, concentration-dependently antagonized the inhibitory effects of testoste rone as well as DHT on PTH-stimulated osteoclast formation. In conclusion, the present study first demonstrated that testosterone inhibited osteoclast formation stimulated by PTH through the androgen receptor, but not through the production of intrinsic estrogen in mouse bone cell cultures, (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Scienc e B,V, All rights reserved.