Publication: Testosterone regulates cardiac contractile activation by modulating SERCA but not NCX activity
Issued Date
2013-02-01
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ISSN
15221539
03636135
03636135
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2-s2.0-84873293059
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Mahidol University
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SCOPUS
Bibliographic Citation
American Journal of Physiology - Heart and Circulatory Physiology. Vol.304, No.3 (2013)
Suggested Citation
Namthip Witayavanitkul, Warunya Woranush, Tepmanas Bupha-Intr, Jonggonnee Wattanapermpool Testosterone regulates cardiac contractile activation by modulating SERCA but not NCX activity. American Journal of Physiology - Heart and Circulatory Physiology. Vol.304, No.3 (2013). doi:10.1152/ajpheart.00555.2012 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/31366
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Title
Testosterone regulates cardiac contractile activation by modulating SERCA but not NCX activity
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Abstract
Alterations in intracellular Ca2+transients of cardiomyocytes in orchidectomized (ORX) rats could be a cause of cardiac dysfunction in the hypogonadal condition. To investigate the role of male sex hormones in intracellular Ca2+homeostasis during relaxation, Ca2+-handling activities by sarco-(endo)plasmic reticulum Ca2+-ATPase (SERCA) and the Na+/Ca2+exchanger (NCX) were evaluated in the ventricular muscle of 10-wk-old ORX rats with and without testosterone supplementation (2.5 mg/kg testosterone propionate, 2 times/wk). ORX induced a 50% decrease in contraction force accompanied by a prolonged time to achieve 50% relaxation (T50) in isolated intact ventricular trabeculae, which was partially corrected by testosterone administration. Maximum active tension was also suppressed in ORX rats without changes in myofilament Ca2+sensitivity and passive stiffness of the heart. Using a sarcoplasmic reticulum-enriched membrane preparation, the maximum thapsigargin-sensitive SERCA activity of the ORX rat was 27% lower with an increased Ca2+sensitivity, which was prevented by testosterone treatment. However, neither changes in SERCA content nor its modulating components, sarcolipin and heat shock protein 20, were detected in the ORX rat, but there was a significant decrease in the phosphorylated Thr17form of phospholamban. Despite a lower level of NCX protein in the heart of ORX rats, prolonged T50 disappeared after an incubation with thapsigargin (10 (xM), implying a lack of effect of male sex hormone deficiency on NCX function. These findings indicate that male sex hormones can regulate cardiac relaxation by acting mainly through SERCA. However, a detailed mechanism of SERCA modulation under male sex hormone deficiency status remains to be explored. © 2013 the American Physiological Society.