Del Punta K, Charreau E H, Pignataro O P
Instituto de Biología y Medicina Experimental-Consejo Nacional de Investigaciones Cientificas y Técnicas and Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Endocrinology. 1996 Dec;137(12):5337-43. doi: 10.1210/endo.137.12.8940355.
Testicular macrophages as well as endothelial cells, which are intimately associated with Leydig cells, constitute a potential source of paracrine nitric oxide (NO) in the testis. In the present study, we investigated the effect of NO donors on MA-10 murine Leydig tumor cell line and rat Leydig cell steroidogenesis. We show that NO donors inhibit human CG-induced steroidogenesis in both type of cells. We also studied NO mechanism of action. Contrary to what is observed in many other systems, NO inhibitory effect on Leydig cell steroidogenesis is not mediated by cyclic GMP (cGMP) because NO fails to increase cGMP production, and cGMP analogs do not reproduce NO effect. NO does not modify the production of cAMP, the main second messenger that mediates gonadotropin action. When we studied NO effect over the steroidogenic pathway in MA-10 cells, we found that NO was inhibiting the conversion of cholesterol to pregnenolone. Taken together these results show an inhibitory effect of NO donors on Leydig cell steroidogenesis, and suggest that NO can be directly inhibiting cholesterol side-chain cleavage enzyme (cytochrome P450scc) as it does with other heme proteins, including different cytochromes P450.
睾丸巨噬细胞以及与睾丸间质细胞密切相关的内皮细胞，构成了睾丸中旁分泌一氧化氮（NO）的潜在来源。在本研究中，我们研究了NO供体对MA - 10小鼠睾丸间质瘤细胞系和大鼠睾丸间质细胞类固醇生成的影响。我们发现NO供体抑制这两种细胞中人类绒毛膜促性腺激素（hCG）诱导的类固醇生成。我们还研究了NO的作用机制。与在许多其他系统中观察到的情况相反，NO对睾丸间质细胞类固醇生成的抑制作用不是由环鸟苷酸（cGMP）介导的，因为NO未能增加cGMP的产生，并且cGMP类似物不能重现NO的作用。NO不会改变环磷酸腺苷（cAMP）的产生，cAMP是介导促性腺激素作用的主要第二信使。当我们研究NO对MA - 10细胞类固醇生成途径的影响时，我们发现NO抑制胆固醇向孕烯醇酮的转化。综上所述，这些结果表明NO供体对睾丸间质细胞类固醇生成具有抑制作用，并表明NO可能像对其他血红素蛋白（包括不同的细胞色素P450）一样，直接抑制胆固醇侧链裂解酶（细胞色素P450scc）。
