title: Testosterone regulates cardiac contractile activation by modulating SERCA but not NCX activity.
abstract: Alterations in intracellular Ca(2+) 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 Ca(2+) homeostasis during relaxation, Ca(2+)-handling activities by sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) and the Na(+)/Ca(2+) 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 (T(50)) 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 Ca(2+) 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 Ca(2+) 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 Thr(17) form of phospholamban. Despite a lower level of NCX protein in the heart of ORX rats, prolonged T(50) disappeared after an incubation with thapsigargin (10 μM), 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.
authors.affiliation: Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Namthip
authors.initials: N
authors.lastname: Witayavanitkul
authors.forename: Warunya
authors.initials: W
authors.lastname: Woranush
authors.forename: Tepmanas
authors.initials: T
authors.lastname: Bupha-Intr
authors.forename: Jonggonnee
authors.initials: J
authors.lastname: Wattanapermpool
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009124:Muscle Proteins / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000187:drug effects; D009200:Myocardial Contraction / Q000502:physiology*; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D011510:Proteolipids / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012518:Sarcomeres / Q000187:drug effects / Q000648:ultrastructure; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000187:drug effects* / Q000502:physiology*; D012669:Seminal Vesicles / Q000187:drug effects; D019831:Sodium-Calcium Exchanger / Q000502:physiology*; D013739:Testosterone / Q000097:blood / Q000494:pharmacology* / Q000502:physiology; D014129:Trabecular Meshwork / Q000502:physiology
chemical_list: D009124:Muscle Proteins; D011510:Proteolipids; D019831:Sodium-Calcium Exchanger; C077258:sarcolipin; D013739:Testosterone; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases