Chen Q, Kaji H, Kanatani M, Sugimoto T, Chihara K
Division of Endocrinology/Metabolism, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Horm Metab Res. 2004 Oct;36(10):674-8. doi: 10.1055/s-2004-826013.
The role that androgens play in the regulation of bone metabolism has been substantiated in animals and humans. We previously demonstrated that testosterone inhibits osteoclast differentiation stimulated by parathyroid hormone through the androgen receptor in mouse bone-cell cultures. However, the details of this mechanism are still unknown. The present study was aimed at examining whether testosterone would affect the mRNA levels of osteoprotegerin (OPG) and receptor activator of Nf kappa B ligand (RANKL) in mouse bone-cell cultures as well as mouse osteoblastic cell-line, MC3T3-E1 cells by employing semi-quantitative RT-PCR. Testosterone increased OPG mRNA expression in both mouse bone-cell cultures and MC3T3-E1 cells. 10-8 M PTH-(1-34) as well as 10-8M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] inhibited OPG mRNA expression in mouse bone cells. 10-8 M testosterone antagonized OPG mRNA expression inhibited by 10-8 M PTH-(1-34), but failed to affect OPG mRNA expression inhibited by 10-8 M 1,25(OH)2D3. 10-8 M alpha-dehydrotestosterone, a non-aromatizable androgen, increased OPG mRNA expression. On the other hand, testosterone did not affect RANKL mRNA expression in MC3T3-E1 or mouse bone cells. In conclusion, the present study demonstrated that testosterone increased OPG mRNA expression in mouse bone-cell cultures and the osteoblastic cell line. These effects are likely to take place through the androgen receptor.
雄激素在骨代谢调节中所起的作用已在动物和人类中得到证实。我们之前证明，在小鼠骨细胞培养物中，睾酮通过雄激素受体抑制甲状旁腺激素刺激的破骨细胞分化。然而，该机制的细节仍不清楚。本研究旨在通过半定量逆转录聚合酶链反应（RT-PCR）检测睾酮是否会影响小鼠骨细胞培养物以及小鼠成骨细胞系MC3T3-E1细胞中骨保护素（OPG）和核因子κB受体活化因子配体（RANKL）的mRNA水平。睾酮增加了小鼠骨细胞培养物和MC3T3-E1细胞中OPG mRNA的表达。10-8 M的甲状旁腺激素（1-34）以及10-8 M的1,25-二羟基维生素D3 [1,25(OH)2D3]抑制了小鼠骨细胞中OPG mRNA的表达。10-8 M的睾酮拮抗了10-8 M甲状旁腺激素（1-34）所抑制的OPG mRNA表达，但未能影响10-8 M 1,25(OH)2D3所抑制的OPG mRNA表达。10-8 M的α-脱氢睾酮，一种不可芳香化的雄激素，增加了OPG mRNA的表达。另一方面，睾酮不影响MC3T3-E1或小鼠骨细胞中RANKL mRNA的表达。总之，本研究表明，睾酮增加了小鼠骨细胞培养物和成骨细胞系中OPG mRNA的表达。这些作用可能是通过雄激素受体发生的。
