Nitric oxide inhibits Leydig cell steroidogenesis

被引:188
作者
DelPunta, K
Charreau, EH
Pignataro, OP
机构
[1] UNIV BUENOS AIRES, INST BIOL & MED EXPT, CONSEJO NACL INVEST CIENT & TECN, RA-1428 BUENOS AIRES, DF, ARGENTINA
[2] UNIV BUENOS AIRES, FAC CIENCIAS EXACTAS & NAT, RA-1428 BUENOS AIRES, DF, ARGENTINA
关键词
D O I
10.1210/en.137.12.5337
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 ad inhibitory effect of NO donors on Leydig cell steroidogenesis, and suggest that NO can be directly inhibiting cholesterol side-chan cleavage enzyme (cytochrome P450(scc)) as it does with other heme proteins, including different cytochromes P450.
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收藏
页码:5337 / 5343
页数:7
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