Endothelial regulation of eNOS, PAI-I and t-PA by testosterone and dihydrotestosterone in vitro and in vivo

Molecular Human Reproduction

Volumn 16, Issue 10, 2010, Pages 761-769

  Goglia, L ^a   Tosi, V ^a   Sanchez, A M ^a   Flamini, M I ^a   Fu, X D ^a   Zullino, S ^a   Genazzani, A R ^a   Simoncini, T ^a  

^a UNIVERSITY OF PISA   (Italy)

Author keywords

Androgens; Cardiovascular disease; Endothelial cells; Fibrinolysis; Nitric oxide

Indexed keywords

ANDROSTANOLONE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; ESTRADIOL; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PHOSPHATIDYLINOSITOL 3 KINASE; PLASMINOGEN ACTIVATOR INHIBITOR 1; TESTOSTERONE; TISSUE PLASMINOGEN ACTIVATOR;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; ENDOTHELIUM CELL; ENZYME ACTIVITY; ENZYME REGULATION; FEMALE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; OVARIECTOMY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RAT; SYNTHESIS;

ANIMALS; CELLS, CULTURED; DIHYDROTESTOSTERONE; ENDOTHELIAL CELLS; FEMALE; HUMANS; IMMUNOBLOTTING; MALE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE III; PLASMINOGEN ACTIVATOR INHIBITOR 1; RATS; RATS, WISTAR; TESTOSTERONE; TISSUE PLASMINOGEN ACTIVATOR;

RATTUS; RATTUS NORVEGICUS;

EID: 77956808588     PISSN: 13609947     EISSN: 14602407     Source Type: Journal    
DOI: 10.1093/molehr/gaq049     Document Type: Article

References (44)

1. Asselbergs FW, Williams SM, Hebert PR, Coffey CS, Hillege HL, Navis G, Vaughan DE, van Gilst WH, Moore JH. Gender-specific correlations of plasminogen activator inhibitor-1 and tissue plasminogen activator levels with cardiovascular disease-related traits. J Thromb Haemost 2007; 5:313-320.
2. Barrett-Connor EL. Testosterone and risk factors for cardiovascular disease in men. Diabete Metab 1995;21:156-161.
3. Basaria S. Prostate cancer: Cardiovascular mortality and androgen deprivation. Nat Rev Urol 2009;6:252-253.
4. Burger HG. Androgen production in women. Fertil Steril 2002;77(Suppl. 4):S3-S5.
5. Cussons AJ, Stuckey BG, Watts GF. Metabolic syndrome and cardiometabolic risk in PCOS. Curr Diab Rep 2007;7:66-73.
6. Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher AM. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 1999;399:601-605.
7. English KM, Mandour O, Steeds RP, Diver MJ, Jones TH, Channer KS. Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms. Eur Heart J 2000;21:890-894.
8. Fu XD, Simoncini T. Non-genomic sex steroid actions in the vascular system. Semin Reprod Med 2007;25:178-186.
9. Fu XD, Simoncini T. Extra-nuclear signaling of estrogen receptors. IUBMB Life 2008;60:502-510.
10. Ganti AK, Potti A, Yegnanarayan R. Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 levels in acute myocardial infarction. Pathophysiol Haemost Thromb 2002;32:80-84.
11. Hak AE, Witteman JC, de Jong FH, Geerlings MI, Hofman A, Pols HA. Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study. J Clin Endocrinol Metab 2002; 87:3632-3639.
12. Harada N, Sasano H, Murakami H, Ohkuma T, Nagura H, Takagi Y. Localized expression of aromatase in human vascular tissues. Circ Res 1999;84:1285-1291.
13. Harrison DG, Widder J, Grumbach I, Chen W, Weber M, Searles C. Endothelial mechanotransduction, nitric oxide and vascular inflammation. J Intern Med 2006;259:351-363.
14. Hatakeyama H, Nishizawa M, Nakagawa A, Nakano S, Kigoshi T, Uchida K. Testosterone inhibits tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression in human aortic endothelial cells. FEBS Lett 2002;530:129-132.
15. Jin H, Lin J, Fu L, Mei YF, Peng G, Tan X, Wang DM, Wang W, Li YG. Physiological testosterone stimulates tissue plasminogen activator and tissue factor pathway inhibitor and inhibits plasminogen activator inhibitor type 1 release in endothelial cells. Biochem Cell Biol 2007; 85:246-251.
16. Juhan-Vague I, Pyke SD, Alessi MC, Jespersen J, Haverkate F, Thompson SG. Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT Study Group. European Concerted Action on Thrombosis and Disabilities. Circulation 1996;94:2057-2063.
17. Kiang JG, Peckham RM, Duke LE, Shimizu T, Chaudry IH, Tsokos GC. Androstenediol inhibits the trauma-hemorrhage-induced increase in caspase-3 by downregulating the inducible nitric oxide synthase pathway. J Appl Physiol 2007;102:933-941.
18. Kimura N, Mizokami A, Oonuma T, Sasano H, Nagura H. Immunocytochemical localization of androgen receptor with polyclonal antibody in paraffin-embedded human tissues. JHistochemCytochem1993;41:671-678.
19. Ling S, Komesaroff PA, Sudhir K. Cardiovascular physiology of androgens and androgen testosterone therapy in postmenopausal women. Endocr Metab Immune Disord Drug Targets 2009;9:29-37.
20. Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab 2004;89:3313-3318.
21. Marin R, Escrig A, Abreu P, Mas M. Androgen-dependent nitric oxide release in rat penis correlates with levels of constitutive nitric oxide synthase isoenzymes. Biol Reprod 1999;61:1012-1016.
22. McCrohon JA, Jessup W, Handelsman DJ, Celermajer DS. Androgen exposure increases human monocyte adhesion to vascular endothelium and endothelial cell expression of vascular cell adhesion molecule-1. Circulation 1999;99:2317-2322.
23. Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. N Engl J Med 1999;340:1801-1811.
24. Mendelsohn ME, Karas RH. Molecular and cellular basis of cardiovascular gender differences. Science 2005;308:1583-1587.
25. Miller KK, Biller BM, Schaub A, Pulaski-Liebert K, Bradwin G, Rifai N, Klibanski A. Effects of testosterone therapy on cardiovascular risk markers in androgen-deficient women with hypopituitarism. J Clin Endocrinol Metab 2007;92:2474-2479.
26. Montalcini T, Gorgone G, Gazzaruso C, Sesti G, Perticone F, Pujia A. Endogenous testosterone and endothelial function in postmenopausal women. Coron Artery Dis 2007;18:9-13.
27. Mukherjee TK, Dinh H, Chaudhuri G, Nathan L. Testosterone attenuates expression of vascular cell adhesion molecule-1 by conversion to estradiol by aromatase in endothelial cells: implications in atherosclerosis. Proc Natl Acad Sci USA 2002;99:4055-4060.
28. Nathan L, Shi W, Dinh H, Mukherjee TK, Wang X, Lusis AJ, Chaudhuri G. Testosterone inhibits early atherogenesis by conversion to estradiol: critical role of aromatase. Proc Natl Acad Sci USA 2001;98:3589-3593.
29. Pober JS, Min W, Bradley JR. Mechanisms of endothelial dysfunction, injury, and death. Annu Rev Pathol 2009;4:71-95.
30. 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 1998;139:922-931.
31. Pugh PJ, Jones RD, West JN, Jones TH, Channer KS. Testosterone treatment for men with chronic heart failure. Heart 2004;90:446-447.
32. Ridker PM. Plasma concentration of endogenous tissue plasminogen activator and the occurrence of future cardiovascular events. J Thromb Thrombolysis 1994;1:35-40.
33. Rosano GM, Leonardo F, Pagnotta P, Pelliccia F, Panina G, Cerquetani E, della Monica PL, Bonfigli B, Volpe M, Chierchia SL. Acute anti-ischemic effect of testosterone in men with coronary artery disease. Circulation 1999;99:1666-1670.
34. Shaw LJ, Bairey Merz CN, Azziz R, Stanczyk FZ, Sopko G, Braunstein GD, Kelsey SF, Kip KE, Cooper-Dehoff RM, Johnson BD et al. Postmenopausal women with a history of irregular menses and elevated androgen measurements at high risk for worsening cardiovascular event-free survival: results from the National Institutes of Health-National Heart, Lung, and Blood Institute sponsored Women's Ischemia Syndrome Evaluation. J Clin Endocrinol Metab 2008; 93:1276-1284.
35. Simoncini T, Hafezi-Moghadam A, Brazil DP, Ley K, Chin WW, Liao JK. Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature 2000;407:538-541.
36. Simoncini T, Mannella P, Fornari L, Varone G, Caruso A, Genazzani AR. Dehydroepiandrosterone modulates endothelial nitric oxide synthesis via direct genomic and nongenomic mechanisms. Endocrinology 2003; 144:3449-3455.
37. Simoncini T, Mannella P, Fornari L, Caruso A, Varone G, Garibaldi S, Genazzani AR. Tibolone activates nitric oxide synthesis in human endothelial cells. J Clin Endocrinol Metab 2004;89:4594-4600.
38. Stallone JN, Salisbury RL, Fulton CT. Androgen-receptor defect abolishes sex differences in nitric oxide and reactivity to vasopressin in rat aorta. J Appl Physiol 2001;91:2602-2610.
39. Sutton-Tyrrell K, Wildman RP, Matthews KA, Chae C, Lasley BL, Brockwell S, Pasternak RC, Lloyd-Jones D, Sowers MF, Torrens JI. Sex-hormone-binding globulin and the free androgen index are related to cardiovascular risk factors in multiethnic premenopausal and perimenopausal women enrolled in the Study of Women Across the Nation (SWAN). Circulation 2005;111:1242-1249.
40. Teede HJ, Hutchison S, Zoungas S, Meyer C. Insulin resistance, the metabolic syndrome, diabetes, and cardiovascular disease risk in women with PCOS. Endocrine 2006;30:45-53.
41. Worboys S, Kotsopoulos D, Teede H, McGrath B, Davis SR. Evidence that parenteral testosterone therapy may improve endothelium-dependent and -independent vasodilation in postmenopausal women already receiving estrogen. J Clin Endocrinol Metab 2001;86:158-161.
42. Wu FC, von Eckardstein A. Androgens and coronary artery disease. Endocr Rev 2003;24:183-217.
43. Zhang X, Wang L, Dou Y, Zhao J, Jiang T, Qiao Z, Qiao J. Testosterone and estradiol modulate TNF-alpha-induced expression of adhesion molecules in endothelial cells. Methods Find Exp Clin Pharmacol 2002a; 24:125-130.
44. Zhang X, Wang LY, Jiang TY, Zhang HP, Dou Y, Zhao JH, Zhao H, Qiao ZD, Qiao JT. Effects of testosterone and 17-beta-estradiol on TNF-alpha-induced E-selectin and VCAM-1 expression in endothelial cells. Analysis of the underlying receptor pathways. Life Sci 2002b; 71:15-29.