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This Article Full Text Full Text (PDF) All Versions of this Article: 291/3/H1101    most recent 00660.2005v1 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 Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Bupha-Intr, T. Articles by Wattanapermpool, J. Search for Related Content PubMed PubMed Citation Articles by Bupha-Intr, T. Articles by Wattanapermpool, J.

Regulatory role of ovarian sex hormones in calcium uptake activity of cardiac sarcoplasmic reticulum

Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand

Submitted 20 June 2005 ; accepted in final form 1 March 2006

Alterations in the intracellular Ca²⁺ handling in cardiomyocytes may underlie the cardiac dysfunction observed in the ovarian sex hormone-deprived condition. To test the hypothesis that ovarian sex hormones had a significant role in the cardiac intracellular Ca²⁺ mobilization, the sarcoplasmic reticulum (SR) Ca²⁺ uptake and SR Ca²⁺-ATPase (SERCA) activity were determined in 10-wk ovariectomized rat hearts. With the use of left ventricular homogenate preparations, a significant suppression of maximum SR Ca²⁺ uptake activity, but with an increase in SR Ca²⁺ responsiveness, was demonstrated in ovariectomized hearts. In parallel measurements of SERCA activity in SR-enriched membrane preparations from ovariectomized hearts, a suppressed maximum SERCA activity with a leftward shift in the relationship between pCa (-log molar free Ca²⁺ concentration) and SERCA activity was also detected. A significant downregulation of SERCA proteins and reduction in the SERCA mRNA level were observed in association with suppressed maximum SERCA activity. While there were no changes in total phospholamban and phosphorylated Ser¹⁶ phospholamban levels, a decrease in phosphorylated Thr¹⁷ phospholamban as well as an increase in the suprainhibitory, monomeric form of phospholamban stoichiometry was found. Estrogen and progesterone supplementations were equally effective in preventing changes in ovariectomized hearts. Our data showed for the first time that female sex hormones played an important role in the regulation of the cardiac SR Ca²⁺ uptake. Under hormone-deficient conditions, there was an adaptive response of SERCA that escaped the regulatory effect of phospholamban.

sarcoplasmic reticulum Ca²⁺-adenosine 5'-triphosphate activity; phospholamban; phosphorylation

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