AJP - Heart AJP: Cell Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol (September 16, 2004). doi:10.1152/ajpheart.00784.2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
288/1/H221    most recent
00784.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, M.
Right arrow Articles by Meldrum, D. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, M.
Right arrow Articles by Meldrum, D. R.
Submitted on August 3, 2004
Accepted on September 14, 2004

THE ROLE OF ENDOGENOUS TESTOSTERONE IN MYOCARDIAL PROINFLAMMATORY AND PROAPOPTOTIC SIGNALING AFTER ACUTE ISCHEMIA-REPERFUSION

Meijing Wang1, Ben M. Tsai1, Ajay Kher1, Lauren B. Baker1, G. Mathenge Wairiuko1, and Daniel R. Meldrum1*

1 Surgery, Cellular and Integrative Physiology, ICVBM, Indiana University Medical Center, Indianapolis, Indiana, USA

* To whom correspondence should be addressed. E-mail: dmeldrum{at}iupui.edu.

Myocardial ischemia is the leading cause of death in both men and women; however, very little information exists regarding the effect of testosterone on the response of myocardium to acute ischemic injury. We hypothesized that testosterone may exert deleterious effects on myocardial inflammatory cytokine production, p38 MAPK activation, apoptotic signaling, and myocardial functional recovery after acute ischemia-reperfusion (I/R). To study this, isolated-perfused rat hearts (Langendorff) from adult males, castrated males and males treated with a testosterone receptor blocker (flutamide) were subjected to 25 minutes of ischemia followed by 40 minutes of reperfusion. Myocardial contractile function (left ventricular developed pressure, left ventricular end diastolic pressure, +dP/dt, -dP/dt) was continuously recorded. After reperfusion, hearts were analyzed for expression of tissue TNF-{alpha} , IL-1{beta} and IL-6 (ELISA), and activation of p38 MAPK, caspase-1, caspase-3, caspase-11 and Bcl-2 (Western blot). All indices of post-ischemic myocardial functional recovery were significantly higher in castrated males or flutamide-treated males compared to untreated males. Following I/R, castrated male and flutamide-treated male hearts had decreased TNF-{alpha}, IL-1{beta} and IL-6; decreased activated p38 MAPK; decreased caspase-1, caspase-3 and caspase-11; and increased Bcl-2 expression compared to untreated males. These results show that blocking the testosterone receptor (flutamide) or depleting testosterone (castration) in normal males improves myocardial function following I/R. These effects may be attributed to the proinflammatory and/or the proapoptotic properties of endogenous testosterone. Further understanding may allow therapeutic manipulation of sex hormone signaling mechanisms in the treatment of acute ischemia-reperfusion.




This article has been cited by other articles:


Home page
 Anesth. Analg.Home page
M. P. Hutchens, J. Dunlap, P. D. Hurn, and P. O. Jarnberg
Renal Ischemia: Does Sex Matter?
Anesth. Analg., July 1, 2008; 107(1): 239 - 249.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
R. Ray, C. M. Herring, T. A. Markel, P. R. Crisostomo, M. Wang, B. Weil, T. Lahm, and D. R. Meldrum
Deleterious effects of endogenous and exogenous testosterone on mesenchymal stem cell VEGF production
Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2008; 294(5): R1498 - R1503.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
P. D. Metcalfe, J. A. Leslie, M. T. Campbell, D. R. Meldrum, K. L. Hile, and K. K. Meldrum
Testosterone exacerbates obstructive renal injury by stimulating TNF-{alpha} production and increasing proapoptotic and profibrotic signaling
Am J Physiol Endocrinol Metab, February 1, 2008; 294(2): E435 - E443.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
D. S. Hydock, C.-Y. Lien, C. M. Schneider, and R. Hayward
Effects of voluntary wheel running on cardiac function and myosin heavy chain in chemically gonadectomized rats
Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3254 - H3264.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
T. Lahm, K. M. Patel, P. R. Crisostomo, T. A. Markel, M. Wang, C. Herring, and D. R. Meldrum
Endogenous estrogen attenuates pulmonary artery vasoreactivity and acute hypoxic pulmonary vasoconstriction: the effects of sex and menstrual cycle
Am J Physiol Endocrinol Metab, September 1, 2007; 293(3): E865 - E871.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
M. Wang, T. Markel, P. Crisostomo, C. Herring, K. K. Meldrum, K. D. Lillemoe, and D. R. Meldrum
Deficiency of TNFR1 protects myocardium through SOCS3 and IL-6 but not p38 MAPK or IL-1beta
Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1694 - H1699.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
R. E. Petre, M. P. Quaile, E. I. Rossman, S. J. Ratcliffe, B. A. Bailey, S. R. Houser, and K. B. Margulies
Sex-based differences in myocardial contractile reserve
Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R810 - R818.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
P. R. Crisostomo, M. Wang, G. M. Wairiuko, E. D. Morrell, and D. R. Meldrum
Brief exposure to exogenous testosterone increases death signaling and adversely affects myocardial function after ischemia
Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2006; 290(5): R1168 - R1174.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
M. A. Cavasin, Z.-Y. Tao, A.-L. Yu, and X.-P. Yang
Testosterone enhances early cardiac remodeling after myocardial infarction, causing rupture and degrading cardiac function
Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H2043 - H2050.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
D. R. Meldrum
Estrogen increases protective proteins following trauma and hemorrhage
Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R809 - R811.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
J. M. Pitcher, M. Wang, B. M. Tsai, A. Kher, N. T. Nelson, and D. R. Meldrum
Endogenous estrogen mediates a higher threshold for endotoxin-induced myocardial protection in females
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R27 - R33.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
M. Wang, B. M. Tsai, M. W. Turrentine, Y. Mahomed, J. W. Brown, and D. R. Meldrum
p38 Mitogen Activated Protein Kinase Mediates Both Death Signaling and Functional Depression in the Heart
Ann. Thorac. Surg., December 1, 2005; 80(6): 2235 - 2241.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
R. Sheppard, M. Bedi, T. Kubota, M. J. Semigran, W. Dec, R. Holubkov, A. M. Feldman, W. D. Rosenblum, C. F. McTiernan, D. M. McNamara, et al.
Myocardial Expression of Fas and Recovery of Left Ventricular Function in Patients With Recent-Onset Cardiomyopathy
J. Am. Coll. Cardiol., September 20, 2005; 46(6): 1036 - 1042.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
A. Kher, K. K. Meldrum, M. Wang, B. M. Tsai, J. M. Pitcher, and D. R. Meldrum
Cellular and molecular mechanisms of sex differences in renal ischemia-reperfusion injury
Cardiovasc Res, September 1, 2005; 67(4): 594 - 603.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.