RGD Reference Report - Testosterone regulates cardiac contractile activation by modulating SERCA but not NCX activity. - Rat Genome Database

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Testosterone regulates cardiac contractile activation by modulating SERCA but not NCX activity.

Authors: Witayavanitkul, N  Woranush, W  Bupha-Intr, T  Wattanapermpool, J 
Citation: Witayavanitkul N, etal., Am J Physiol Heart Circ Physiol. 2013 Feb 1;304(3):H465-72. doi: 10.1152/ajpheart.00555.2012. Epub 2012 Nov 30.
RGD ID: 7327180
Pubmed: PMID:23203968   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpheart.00555.2012   (Journal Full-text)

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 muM), 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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to testosterone  IDA 7327180 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pln  (phospholamban)


Additional Information