This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, J. Articles by Wong, T. M. Search for Related Content PubMed PubMed Citation Articles by Liu, J. Articles by Wong, T. M.

Testosterone Is Required for Delayed Cardioprotection and Enhanced Heat Shock Protein 70 Expression Induced by Preconditioning

Department of Physiology and Institute of Cardiovascular Sciences and Medicine, The University of Hong Kong, Hong Kong SAR, China

Address all correspondence and requests for reprints to: Professor T. M. Wong, Ph.D., Department of Physiology, Faculty of Medicine, The University of Hong Kong, 4/F Laboratory Block, Faculty of Medicine Buildings, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China. E-mail: wongtakm{at}hkucc.hku.hk.

Ischemic preconditioning fails to confer immediate cardioprotection in the absence of testosterone, indicating that the hormone is required for the process. Here we set out to determine whether testosterone is also necessary for delayed cardioprotection and, if so, how it acts. Male Sprague Dawley rats (7–8 wk) underwent sham operation or gonadectomy without (G) or with testosterone replacement (GT) for 8 wk. Isolated ventricular myocytes were preconditioned either by metabolic inhibition or with U50,488H, a -opioid receptor agonist. In intact rats, U50,488H was administered systemically and 24 h later the hearts were removed. Ventricular myocytes were then subjected to metabolic inhibition and anoxia and isolated hearts to regional ischemia, followed by reperfusion to induce injury. Both types of preconditioning significantly increased the viability and decreased the lactate dehydrogenase release in ventricular myocytes from sham rats. They also activated heat shock transcription factor-1 and increased heat shock protein 70 expression. In contrast, all these effects were absent in myocytes from G rats and were restored by testosterone replacement. Parallel results were found in isolated hearts. In addition, preconditioning improved contractile functions impaired by ischemic insults in sham and rats gonadectomized with testosterone replacement but not G rats. The effects of testosterone replacement in ventricular myocytes were abolished by androgen receptor blockade. In conclusion, preconditioning requires testosterone to increase heat shock protein 70 synthesis, which mediates delayed cardioprotection in the male. These effects of testosterone are mediated by the androgen receptor.

This article has been cited by other articles:

				S. Tsang, S. S. C. Wong, S. Wu, G. M. Kravtsov, and T.-M. Wong Testosterone-augmented contractile responses to {alpha}1- and {beta}1-adrenoceptor stimulation are associated with increased activities of RyR, SERCA, and NCX in the heart Am J Physiol Cell Physiol, April 1, 2009; 296(4): C766 - C782. [Abstract] [Full Text] [PDF]

				H.-J. Lee and J. Teixeira Evidence of a Role for Androgens in Embryonic Stem Cell Function and Differentiation Endocrinology, January 1, 2008; 149(1): 3 - 4. [Full Text] [PDF]

				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]

				H. Kohno, N. Takahashi, T. Shinohara, T. Ooie, K. Yufu, M. Nakagawa, H. Yonemochi, M. Hara, T. Saikawa, and H. Yoshimatsu Receptor-Mediated Suppression of Cardiac Heat-Shock Protein 72 Expression by Testosterone in Male Rat Heart Endocrinology, July 1, 2007; 148(7): 3148 - 3155. [Abstract] [Full Text] [PDF]