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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 P450(scc)) as it does with other heme proteins, including different cytochromes P459.


Documento: Artículo
Título:Nitric oxide inhibits leydig cell steroidogenesis
Autor:Del Punta, K.; Charreau, E.H.; Pignataro, O.P.
Filiación:Inst. Biol. y Med. Exp.-Consejo N., Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Inst. de Biol. y Med. Experimental, Obligado 2490, 1428 Buenos Aires, Argentina
Palabras clave:cholesterol; cholesterol monooxygenase (side chain cleaving); chorionic gonadotropin; cyclic AMP; cyclic GMP; cytochrome P450; diethylamine; diethylenetriamine; hemoprotein; nitric oxide; nitric oxide donor; pregnenolone; steroid; animal cell; article; autocrine effect; controlled study; Leydig cell; Leydig cell tumor; male; mouse; nonhuman; priority journal; rat; second messenger; steroidogenesis; testosterone synthesis
Página de inicio:5337
Página de fin:5343
Título revista:Endocrinology
Título revista abreviado:ENDOCRINOLOGY
CAS:cholesterol, 57-88-5; cholesterol monooxygenase (side chain cleaving), 37292-81-2; chorionic gonadotropin, 9002-61-3; cyclic AMP, 60-92-4; cyclic GMP, 7665-99-8; cytochrome P450, 9035-51-2; diethylamine, 109-89-7, 660-68-4; diethylenetriamine, 111-40-0; nitric oxide, 10102-43-9; pregnenolone, 145-13-1


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---------- APA ----------
Del Punta, K., Charreau, E.H. & Pignataro, O.P. (1996) . Nitric oxide inhibits leydig cell steroidogenesis. Endocrinology, 137(12), 5337-5343.
---------- CHICAGO ----------
Del Punta, K., Charreau, E.H., Pignataro, O.P. "Nitric oxide inhibits leydig cell steroidogenesis" . Endocrinology 137, no. 12 (1996) : 5337-5343.
---------- MLA ----------
Del Punta, K., Charreau, E.H., Pignataro, O.P. "Nitric oxide inhibits leydig cell steroidogenesis" . Endocrinology, vol. 137, no. 12, 1996, pp. 5337-5343.
---------- VANCOUVER ----------
Del Punta, K., Charreau, E.H., Pignataro, O.P. Nitric oxide inhibits leydig cell steroidogenesis. ENDOCRINOLOGY. 1996;137(12):5337-5343.