Zimniski S J, Brandt M E, Melner M H, Covey D F, Puett D
Cancer Res. 1985 Oct;45(10):4883-9.
The murine Leydig cell tumor (M5480A) was assayed for the presence of aromatase activity and for the effects of 10-propargylestr-4-ene-3,17-dione (PED), an aromatase inhibitor, on steroidogenesis. Microsomal preparations from these tumors contained low levels of aromatase activity which was PED sensitive. In addition, these Leydig tumor cells were maintained in primary culture and incubated under basal and gonadotropin-stimulated conditions with various doses of PED. Medium levels of progesterone, a major product of these cells, were found to decrease in a dose- and time-dependent manner upon addition of PED. To determine whether the observed effect was due to reduced synthesis or to increased metabolism of progesterone, tritiated progesterone was added to these cell cultures. Analysis of culture medium by high-performance liquid chromatography suggested that PED dramatically reduced the conversion of labeled progesterone to testosterone. Furthermore, examination of medium pregnenolone levels revealed diminished amounts of this steroid as well. Taken together, these results suggest that PED or its metabolites inhibit Leydig tumor cell steroidogenesis at several sites. Thus, in addition to its role as an aromatase inhibitor, this agent also has effects prior to pregnenolone production, as well as other effects in the pathway between progesterone and testosterone.
对小鼠睾丸间质细胞瘤（M5480A）进行了芳香化酶活性检测以及芳香化酶抑制剂10-丙炔基雌甾-4-烯-3,17-二酮（PED）对类固醇生成作用的研究。这些肿瘤的微粒体制剂含有低水平的芳香化酶活性，且该活性对PED敏感。此外，将这些睾丸间质肿瘤细胞进行原代培养，并在基础和促性腺激素刺激条件下用不同剂量的PED孵育。发现这些细胞的主要产物孕酮的培养基水平在添加PED后呈剂量和时间依赖性下降。为了确定观察到的效应是由于孕酮合成减少还是代谢增加所致，向这些细胞培养物中加入了氚标记的孕酮。通过高效液相色谱法对培养基进行分析表明，PED显著降低了标记孕酮向睾酮的转化。此外，对培养基中孕烯醇酮水平的检测也显示该类固醇的量减少。综上所述，这些结果表明PED或其代谢产物在多个位点抑制睾丸间质肿瘤细胞的类固醇生成。因此，除了作为芳香化酶抑制剂的作用外，该药物在孕烯醇酮生成之前也有作用，以及在孕酮和睾酮之间的途径中还有其他作用。
