Del Punta K, Sanchez-Ruiz M E, Pignataro O P
Instituto de Biología y Medicina Experimental-CONICET, Buenos Aires.
Medicina (B Aires). 1997;57(3):337-40.
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 present study, we investigated the effect of NO donors on MA-10 murine Leydig tumor cell line and rat Leydig cell steroidogenesis. We observed that NO donors, reversibly inhibit hCG-induced steroidogenesis in both types 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 cGMP, as 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 is 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 P-450 scc) as it does with other heme proteins, including different cytochromes P-450.
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小鼠睾丸间质细胞瘤细胞系和大鼠睾丸间质细胞类固醇生成的影响。我们观察到，NO供体可可逆地抑制两种细胞中hCG诱导的类固醇生成。我们还研究了NO的作用机制。与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cGMP介导的，因为NO无法增加cGMP的产生，且cGMP类似物也无法重现NO的作用。NO不会改变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。综合这些结果表明，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P-450）一样，直接抑制胆固醇侧链裂解酶（细胞色素P-450 scc）。
