Kasperk C, Fitzsimmons R, Strong D, Mohan S, Jennings J, Wergedal J, Baylink D
Department of Medicine, Jerry L. Pettis Memorial Veterans Hospital, Loma Linda, California.
J Clin Endocrinol Metab. 1990 Nov;71(5):1322-9. doi: 10.1210/jcem-71-5-1322.
Recently, we reported a direct effect of androgens on murine and human bone cells to stimulate bone cell proliferation and differentiation. To test whether this effect of androgenic steroids might be mediated by growth factors, we measured relative concentrations of insulin-like growth factor-I and -II (IGF-I and IGF-II) and transforming growth factor-beta (TGF beta) in the conditioned medium from androgen-treated murine calvarial cell cultures. Only the concentration of TGF beta was increased. Consistent with the increased secretion of TGF beta in the mouse calvarial cell system, we observed an increased expression of TGF beta mRNA in a normal human osteoblastic cell system. We also determined whether androgens alter the response to growth factors. We found that dihydrotestosterone (DHT) treatment enhanced the mitogenic effects of fibroblast growth factor (FGF) and IGF-II but not those of IGF-I. The enhanced effect of FGF and IGF-II after DHT pretreatment was not affected by addition of TGF beta-blocking antibodies or by changing the culture medium. This indicated that in addition to increased release of TGF beta, another mechanism might be involved in the action of DHT on human and murine bone cells. Thus, we investigated the binding of human IGF-II to human osteoblastic cells and observed an increase in IGF-II binding after DHT treatment. Our results are consistent with a mechanism of action of androgens on bone cells that involves the induction of TGF beta and, in addition, may sensitize the cells to show an enhanced response to FGF and IGF-II, possibly by changing the receptor binding of mitogenic growth factors.
最近，我们报道了雄激素对小鼠和人类骨细胞有直接作用，可刺激骨细胞增殖和分化。为了测试雄激素类固醇的这种作用是否可能由生长因子介导，我们测量了雄激素处理的小鼠颅盖细胞培养条件培养基中胰岛素样生长因子-I和-II（IGF-I和IGF-II）以及转化生长因子-β（TGFβ）的相对浓度。只有TGFβ的浓度增加。与小鼠颅盖细胞系统中TGFβ分泌增加一致，我们在正常人成骨细胞系统中观察到TGFβ mRNA表达增加。我们还确定了雄激素是否会改变对生长因子的反应。我们发现，双氢睾酮（DHT）处理增强了成纤维细胞生长因子（FGF）和IGF-II的促有丝分裂作用，但未增强IGF-I的促有丝分裂作用。DHT预处理后FGF和IGF-II的增强作用不受添加TGFβ阻断抗体或更换培养基的影响。这表明，除了TGFβ释放增加外，另一种机制可能参与了DHT对人和小鼠骨细胞的作用。因此，我们研究了人IGF-II与人成骨细胞的结合，观察到DHT处理后IGF-II结合增加。我们的结果与雄激素对骨细胞的作用机制一致，该机制涉及TGFβ的诱导，此外，可能通过改变有丝分裂生长因子的受体结合使细胞对FGF和IGF-II表现出增强的反应。
