Kasperk C H, Wergedal J E, Farley J R, Linkhart T A, Turner R T, Baylink D J
Department of Medicine, Loma Linda University, CA 92357.
Endocrinology. 1989 Mar;124(3):1576-8. doi: 10.1210/endo-124-3-1576.
This report describes the first observation of a direct mitogenic effect of androgens on isolated osteoblastic cells in serum-free culture. [3H]thymidine incorporation into DNA and cell counts were used as measures of cell proliferation. The percentage of cells that stained for alkaline phosphatase was used as a measure of differentiation. Dihydrotestosterone (DHT) enhanced mouse osteoblastic cell proliferation in a dose dependent manner over a wide range of doses (10(-8) to 10(-11) molar), and was maximally active at 10(-9) M. DHT also stimulated proliferation in human osteoblast cell cultures and in cultures of the human osteosarcoma cell line, TE89. Testosterone, fluoxymesterone (a synthetic androgenic steroid) and methenolone (an anabolic steroid) were also mitogenic in the mouse bone cell system. The mitogenic effect of DHT on bone cells was inhibited by antiandrogens (hydroxyflutamide and cyproterone acetate) which compete for binding to the androgen receptor. In addition to effects on cell proliferation, DHT increased the percentage of alkaline phosphatase (ALP) positive cells in all three bone cell systems tested, and this effect was inhibited by antiandrogens. We conclude that androgens can stimulate human and murine osteoblastic cell proliferation in vitro, and induce expression of the osteoblast-line differentiation marker ALP, presumably by an androgen receptor mediated mechanism.
本报告描述了首次观察到雄激素在无血清培养中对分离的成骨细胞有直接促有丝分裂作用。[3H]胸腺嘧啶核苷掺入DNA及细胞计数被用作细胞增殖的指标。碱性磷酸酶染色阳性的细胞百分比被用作分化的指标。双氢睾酮（DHT）在很宽的剂量范围（10^(-8)至10^(-11)摩尔）内以剂量依赖方式增强小鼠成骨细胞增殖，在10^(-9) M时活性最大。DHT也刺激人成骨细胞培养物及人骨肉瘤细胞系TE89的增殖。睾酮、氟甲睾酮（一种合成雄激素类固醇）及美替诺龙（一种合成代谢类固醇）在小鼠骨细胞系统中也有促有丝分裂作用。DHT对骨细胞的促有丝分裂作用被与雄激素受体竞争结合的抗雄激素（羟基氟他胺和醋酸环丙孕酮）所抑制。除了对细胞增殖的影响外，DHT在所有三个受试骨细胞系统中均增加了碱性磷酸酶（ALP）阳性细胞的百分比，且此作用被抗雄激素所抑制。我们得出结论，雄激素可在体外刺激人和小鼠成骨细胞增殖，并诱导成骨细胞系分化标志物ALP的表达，推测是通过雄激素受体介导的机制。
