Sildenafil treatment in vivo stimulates Leydig cell steroidogenesis via the cAMP/cGMP signaling pathway

American Journal of Physiology - Endocrinology and Metabolism

Volumn 299, Issue 4, 2010, Pages

  Andric, Silvana A ^a   Janjic, Marija M ^a   Stojkov, Natasa J ^a   Kostic, Tatjana S ^a  

^a UNIVERSITY OF NOVI SAD   (Serbia)

Author keywords

Cyclic adenosine monophosphate; Cyclic guanosine monophosphate; Steroidogenic acute regulatory protein

Indexed keywords

CHORIONIC GONADOTROPIN; CYCLIC AMP; CYCLIC GMP; GUANYLATE CYCLASE; NITRIC OXIDE DONOR; NITRIC OXIDE SYNTHASE; PHOSPHODIESTERASE; PROTEIN KINASE; PROTEIN KINASE G1; SILDENAFIL; STEROIDOGENIC ACUTE REGULATORY PROTEIN; TESTOSTERONE; UNCLASSIFIED DRUG; CYCLIC GMP DEPENDENT PROTEIN KINASE; INDUCIBLE NITRIC OXIDE SYNTHASE; MESSENGER RNA; NOS2 PROTEIN, RAT; PHOSPHODIESTERASE INHIBITOR; PHOSPHODIESTERASE V; PHOSPHODIESTERASE V INHIBITOR; PIPERAZINE DERIVATIVE; PURINE DERIVATIVE; SULFONE;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG EFFECT; ENZYME ACTIVITY; GENE; GUCY1A1 GENE; GUCY1B1 GENE; IN VIVO STUDY; LEYDIG CELL; MALE; NONHUMAN; NOS2 GENE; NOS3 GENE; PDE1C GENE; PDE4A GENE; PDE5 GENE; PDE6C GENE; PKG1 GENE; PRIORITY JOURNAL; RAT; SIGNAL TRANSDUCTION; STEROIDOGENESIS; TESTOSTERONE BLOOD LEVEL; TESTOSTERONE SYNTHESIS; ANIMAL; BIOSYNTHESIS; CHEMISTRY; CYTOLOGY; DRUG EFFECTS; ENZYMOLOGY; GENETICS; METABOLISM; NONPARAMETRIC TEST; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TESTIS; WISTAR RAT;

ANIMALS; CYCLIC AMP; CYCLIC GMP; CYCLIC GMP-DEPENDENT PROTEIN KINASES; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 5; GUANYLATE CYCLASE; LEYDIG CELLS; MALE; NITRIC OXIDE SYNTHASE TYPE II; PHOSPHODIESTERASE INHIBITORS; PIPERAZINES; PURINES; RATS; RATS, WISTAR; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, MESSENGER; SIGNAL TRANSDUCTION; STATISTICS, NONPARAMETRIC; SULFONES; TESTIS; TESTOSTERONE; PHOSPHODIESTERASE 5 INHIBITORS;

EID: 77957602396     PISSN: 01931849     EISSN: 15221555     Source Type: Journal    
DOI: 10.1152/ajpendo.00337.2010     Document Type: Article

References (41)

1. Andric SA, Janjic MM, Stojkov NJ, Kostic TS. Protein kinase G-mediated stimulation of basal Leydig cell steroidogenesis. Am J Physiol Endocrinol Metab 293: E1399-E1408, 2007.
2. Andric SA, Janjic MM, Stojkov NJ, Kostic TS. Testosterone-induced modulation of nitric oxide-cGMP signaling pathway and androgenesis in the rat Leydig cells. Biol Reprod. doi:10.1095/biolreprod.110.083626, 2007.
3. Ballard SA, Gingell CJ, Tang K, Turner LA, Price ME, Naylor AM. Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. J Urol 159: 2164-2171, 1998. (Pubitemid 29190800)
4. Bustin SA. Quantificaion of mRNA using real-time reverse transcription PCR (RT-PCR): trends and problems. J Mol Endocrinol 29: 23-39, 2002.
5. Carosa E, Martini P, Brandetti F, Di Stasi SM, Lombardo F, Lenzi A, Jannini EA. Type V phosphodiesterase inhibitor treatments for erectile dysfunction increase testosterone levels. Clin Endocrinol (Oxf) 61: 382-386, 2004. (Pubitemid 39287069)
6. Catt KJ, Dufau ML. Spare gonadotropin receptors in rat testis. Nat New Biol 244: 219-221, 1973.
7. Clark BJ, Wells J, King SR, Stocco DM. The purification, cloning, and expression of a novel luteinizing hormone-induced mitochondrial protein in MA-10 mouse Leydig tumor cells. Characterization of the steroidogenic acute regulatory protein (StAR). J Biol Chem 269: 28314-28322, 1994.
8. Davidoff MS, Middendorff R, Mayer B, deVente J, Koesling D, Holstein AF. Nitric oxide/cGMP pathway components in the Leydig cells of the human testis. Cell Tissue Res 287: 161-170, 1997.
9. Del Punta K, Charreau EH, Pignataro OP. Nitric oxide inhibits Leydig cell steroidogenesis. Endocrinology 137: 5337-5343, 1996. (Pubitemid 26423094)
10. Drewett JG, Adams-Hays RL, Ho BY, Hegge DJ. Nitric oxide potently inhibits the rate-limiting enzymatic step in steroidogenesis. Mol Cell Endocrinol 194: 39-50, 2002.
11. Dufau ML. The luteinizing hormone receptor. Annu Rev Physiol 60: 461-496, 1998.
12. Fischmeister R, Castro LR, Abi-Gerges A, Rochais F, Jurevicius J, Leroy J, Vandecasteele G. Compartmentation of cyclic nucleotide signaling in the heart: the role of cyclic nucleotide phosphodiesterases. Circ Res 99: 816-828, 2006. (Pubitemid 44556380)
13. Gambaryan S, Butt E, Marcus K, Glazova M, Palmetshofer A, Guillon G, Smolenski A. cGMP-dependent protein kinase type II regulates basal level of aldosterone production by zona glomerulosa cells without increasing expression of the steroidogenic acute regulatory protein gene. J Biol Chem 278: 29640-29648, 2003.
14. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 126: 131-138, 1982.
15. Hales KH, Diemer T, Ginde S, Shankar BK, Roberts M, Bosmann HB, Hales DB. Diametric effects of bacterial endotoxin lipopolysaccharide on adrenal and Leydig cell steroidogenic acute regulatory protein. Endocrinology 141: 4000-4012, 2000.
16. Heidelbaugh JJ. Management of erectile dysfunction. Am Fam Physician 81: 305-312, 2010.
17. Kim D, Rybalkin SD, Pi X, Wang Y, Zhang C, Munzel T, Beavo JA, Berk BC, Yan C. Upregulation of phosphodiesterase 1A1 expression is associated with the development of nitrate tolerance. Circulation 104: 2338-2343, 2001. (Pubitemid 33049518)
18. Kostic TS, Andric SA, Stojilkovic SS. Spontaneous and receptor-controlled soluble guanylyl cyclase activity in anterior pituitary cells. Mol Endocrinol 15: 1010-1022, 2001.
19. Kostic TS, Stojkov NJ, Janjic MM, Maric D, Andric SA. The adaptive response of adult rat Leydig cells to repeated immobilization stress: the role of protein kinase A and steroidogenic acute regulatory protein. Stress 11: 370-380, 2008.
20. Kostic TS, Stojkov NJ, Janjic MM, Andric SA. Structural complexity of the testis and PKG-I/StAR interaction regulate the Leydig cell adaptive response to repeated immobilization stress. Int J Androl; doi:10.1111/j.1365-2605.2009. 01018.
21. Liu J, Rone MB, Papadopoulos V. Protein-protein interactions mediate mitochondrial cholesterol transport and steroid biosynthesis. J Biol Chem 281: 38879-38893, 2006.
22. Martinez-Arguelles DB, Papadopoulos V. Epigenetic regulation of the expression of genes involved in steroid hormone biosynthesis and action. Steroids 75: 467-476, 2010.
23. Mostafa T, Rashed LA, Kotb K. Testosterone and chronic sildenafil/ tadalafil anti-apoptotic role in aged diabetic rats. Int J Impot Res 22: 255-261, 2010.
24. Payne AH, Downing JR, Wong KL. Luteinizing hormone receptors and testosterone synthesis in two distinct populations of Leydig cells. Endocrinology 106: 1424-1429, 1980.
25. Payne AH, Hales DB. Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocr Rev 25: 947-970, 2004.
26. Pomerantz DK, Pitelka V. Nitric oxide is a mediator of the inhibitory effect of activated macrophages on production of androgen by the Leydig cell of the mouse. Endocrinology 139: 922-931, 1998. (Pubitemid 28510106)
27. Reinhart AJ, Williams SC, Stocco DM. Transcriptional regulation of the StAR gene. Mol Cell Endocrinol 151: 161-169, 1999.
28. Rybalkin SD, Rybalkina IG, Feil R, Hofmann F, Beavo JA. Regulation of cGMP-specific phosphodiesterase (PDE5) phosphorylation in smooth muscle cells. J Biol Chem 277: 3310-33174, 2002.
29. Rybalkin SD, Yan C, Bornfeldt KE, Beavo JA. Cyclic GMP phosphodiesterases and regulation of smooth muscle function. Circ Res 93: 280-291, 2003. (Pubitemid 37048240)
30. Saez JM. Leydig cells: endocrine, paracrine, and autocrine regulation. Endocr Rev 15: 574-626, 1994.
31. Saraiva KL, Silva AK, Wanderley MI, De Araújo AA, De Souza JR, Peixoto CA. Chronic treatment with sildenafil stimulates Leydig cell and testosterone secretion. Int J Exp Pathol 90: 454-462, 2009.
32. Schlossmann J, Desch M. cGK substrates. Handb Exp Pharmacol 191: 163-193, 2009.
33. Scipioni A, Stefanini S, Santone R, Giorgi M. Immunohistochemical localisation of PDE5 in Leydig and myoid cells of prepuberal and adult rat testis. Histochem Cell Biol 124: 401-417, 2005.
34. Sewer MB, Jagarlapudi S. Complex assembly on the human CYP17 promoter. Mol Cell Endocrinol 300: 109-114, 2009.
35. Sharma R. Novel phosphodiesterase-5 inhibitors: current indications and future directions. Indian J Med Sci 61: 667-679, 2007.
36. Stocco DM, Wang X, Jo Y, Manna PR. Multiple signaling pathways regulating steroidogenesis and steroidogenic acute regulatory protein expression: more complicated than we thought. Mol Endocrinol 19: 2647-2659, 2005. (Pubitemid 41577240)
37. Tremblay JJ, Hamel F, Viger RS. Protein kinase A-dependent cooperation between GATA and CCAAT/enhancer-binding protein transcription factors regulates steroidogenic acute regulatory protein promoter activity. Endocrinology 143: 3935-3945, 2002. (Pubitemid 35244373)
38. Valenti S, Cuttica CM, Fazzuoli L, Giordano G, Giusti M. Biphasic effect of nitric oxide on testosterone and cyclic GMP production by purified rat Leydig cells cultured in vitro. Int J Androl 22: 336-341, 1999. (Pubitemid 29445890)
39. Veenman L, Papadopoulos V, Gavish M. Channel-like functions of the 18-kDa translocator protein (TSPO): regulation of apoptosis and steroidogenesis as part of the host-defense response. Curr Pharm Des 13: 2385-2405, 2007. (Pubitemid 47321571)
40. Weissman BA, Niu E, Ge R, Sottas CM, Holmes M, Hutson JC, Hardy MP. Paracrine modulation of androgen synthesis in rat Leydig cells by nitric oxide. J Androl 26: 369-378, 2005. (Pubitemid 40628974)
41. Zhao L, Manson NA, Strange JW, Walker H, Wilkings MR. Beneficial effects of phosphodiesterase 5 inhibition in pulmonary hypertension are influenced by natriuretic peptide activity. Circulation 107: 234-237, 2003. (Pubitemid 36135217)