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Abstract:

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 hGG-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-450scc) as it does with other heme proteins, including different cytochromes P-450.

Registro:

Documento: Artículo
Título:Regulation of testicular steroidogenesis by nitric oxide
Autor:Del Punta, K.; Sanchez-Ruiz, M.E.; Pignataro, O.P.
Filiación:Inst. de Biol. y Med. Experimental, CONICET, Buenos Aires, Argentina
Inst. de Biol. y Med. Experimental, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina
Palabras clave:cholesterol; cholesterol monooxygenase (side chain cleaving); chorionic gonadotropin; cyclic gmp; cyclic gmp derivative; hemoprotein; nitric oxide; nitric oxide donor; pregnenolone; nitric oxide; steroid; animal cell; animal tissue; article; inhibition kinetics; leydig cell; macrophage activation; mouse; nonhuman; pathophysiology; rat; second messenger; steroidogenesis; testis cell; animal; biosynthesis; disease model; Leydig cell tumor; male; metabolism; physiology; Sprague Dawley rat; testis tumor; Animals; Disease Models, Animal; Leydig Cell Tumor; Male; Mice; Nitric Oxide; Rats; Rats, Sprague-Dawley; Steroids; Testicular Neoplasms
Año:1997
Volumen:57
Número:3
Página de inicio:337
Página de fin:340
Título revista:Medicina
Título revista abreviado:MEDICINA (ARGENTINA)
ISSN:00257680
CODEN:MEDCA
CAS:cholesterol monooxygenase (side chain cleaving), 37292-81-2; cholesterol, 57-88-5; chorionic gonadotropin, 9002-61-3; cyclic GMP, 7665-99-8; nitric oxide, 10102-43-9; pregnenolone, 145-13-1; Nitric Oxide, 10102-43-9; Steroids
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00257680_v57_n3_p337_DelPunta

Referencias:

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  • Nathan, C.F., Nitric oxide as a secretory product of mammalian cells (1992) FASEB J, 6, pp. 3051-3064
  • Bredt, D.S., Snyder, S.H., Nitric oxide: A physiologic messenger molecule (1994) Ann Rev Biochem, 63, pp. 175-195
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  • Wink, D.A., Osawa, Y., Darbyshire, J.F., Collins, R.J., Eshenaur, S.C., Nims, R.W., Inhibition of cytochromes P450 by nitric oxide and a nitric oxide-releasing agent (1993) Arch Biochem Biophys, 300, pp. 115-123
  • Ascoli, M., Pignataro, O.P., Segaloff, D.L., The inosiltol phosphate/diacylglicerol pathway in MA-10 Leydig tumor cells. Activation by arginine vasopressin and lack of effect of epidermal growth factor and human choriogonadotropin (1989) J Biol Chem, 264, pp. 6674-6681
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  • Pandey, K.N., Kovacs, W.J., Inagami, T., The inhibition of progesterone secretion and the regulation of cyclic nucleotides by atrial natriuretic factor in gonadotropin responsive murine Leydig tumor cells (1985) Biochem Biophy Res Commun, 133, pp. 800-806
  • Pollock, J.S., Forstermann, U., Mitchell, J.A., Warner, T.D., Schmidt, H.H., Nakane, M., Murad, F., Purification and characterization of particulate endothelium-derived relaxing factor synthase from cultured and native bovine aortic endothelial cells Proc Natl Acad Sci USA, 88, pp. 10480-10484
  • Stuehr, D.J., Cho, H.J., Kwon, N.S., Weise, M.F., Nathan, C.F., Purification and characterization of the cytokine-induced macrophage nitric oxide synthase: An FAD- and FMN-containing flavoprotein (1991) Proc Natl Acad Sci USA, 88, pp. 7773-7777
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Citas:

---------- APA ----------
Del Punta, K., Sanchez-Ruiz, M.E. & Pignataro, O.P. (1997) . Regulation of testicular steroidogenesis by nitric oxide. Medicina, 57(3), 337-340.
Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00257680_v57_n3_p337_DelPunta [ ]
---------- CHICAGO ----------
Del Punta, K., Sanchez-Ruiz, M.E., Pignataro, O.P. "Regulation of testicular steroidogenesis by nitric oxide" . Medicina 57, no. 3 (1997) : 337-340.
Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00257680_v57_n3_p337_DelPunta [ ]
---------- MLA ----------
Del Punta, K., Sanchez-Ruiz, M.E., Pignataro, O.P. "Regulation of testicular steroidogenesis by nitric oxide" . Medicina, vol. 57, no. 3, 1997, pp. 337-340.
Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00257680_v57_n3_p337_DelPunta [ ]
---------- VANCOUVER ----------
Del Punta, K., Sanchez-Ruiz, M.E., Pignataro, O.P. Regulation of testicular steroidogenesis by nitric oxide. MEDICINA (ARGENTINA). 1997;57(3):337-340.
Available from: https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00257680_v57_n3_p337_DelPunta [ ]