Early testosterone replacement attenuates intracellular calcium dyshomeostasis in the heart of testosterone-deprived male rats

© 2017 Elsevier Ltd Background Testosterone deficiency in elderly men increases the risk of cardiovascular disease. In bilateral orchiectomized (ORX) animals, impaired cardiac Ca2+regulation was observed, and this impairment could be improved by testosterone replacement, indicating the important rol...

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Main Authors: Punate Weerateerangkul, Krekwit Shinlapawittayatorn, Siripong Palee, Nattayaporn Apaijai, Siriporn C. Chattipakorn, Nipon Chattipakorn
Format: Journal
Published: 2018
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/56672
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spelling th-cmuir.6653943832-566722018-09-05T03:28:44Z Early testosterone replacement attenuates intracellular calcium dyshomeostasis in the heart of testosterone-deprived male rats Punate Weerateerangkul Krekwit Shinlapawittayatorn Siripong Palee Nattayaporn Apaijai Siriporn C. Chattipakorn Nipon Chattipakorn Biochemistry, Genetics and Molecular Biology © 2017 Elsevier Ltd Background Testosterone deficiency in elderly men increases the risk of cardiovascular disease. In bilateral orchiectomized (ORX) animals, impaired cardiac Ca2+regulation was observed, and this impairment could be improved by testosterone replacement, indicating the important role of testosterone in cardiac Ca2+regulation. However, the temporal changes of Ca2+dyshomeostasis in testosterone-deprived conditions are unclear. Moreover, the effects of early vs. late testosterone replacement are unknown. We hypothesized that the longer the deprivation of testosterone, the greater the impairment of cardiac Ca2+homeostasis, and that early testosterone replacement can effectively reduce this adverse effect. Methods Male Wistar rats were randomly divided into twelve groups, four sets of three. The first set were ORX for 2, 4 and 8 weeks, the second set were sham-operated groups of the same periods, the third set were ORX for 8 weeks coupled with a subcutaneous injection of vehicle (control), testosterone during weeks 1–8 (early replacement) or testosterone during weeks 5–8 (late replacement), and finally the 12-week sham-operated, ORX and ORX treated with testosterone groups. Cardiac Ca2+transients (n = 4-5/group), L-type calcium current (ICa-L) (n = 4/group), Ca2+regulatory proteins (n = 6/group) and cardiac function (n = 5/group) were determined. Results In the ORX rats, impaired cardiac Ca2+transients and reduced ICa-Lwere observed initially 4 weeks after ORX as shown by decreased Ca2+transient amplitude, rising rate and maximum and average decay rates. No alteration of Ca2+regulatory proteins such as the L-type Ca2+channels, ryanodine receptor type 2, Na+-Ca2+exchangers and SERCA2a were observed. Early testosterone replacement markedly improved cardiac Ca2+transients, whereas late testosterone replacement did not. The cardiac contractility was also improved after early testosterone replacement. Conclusions Impaired cardiac Ca2+homeostasis is time-dependent after testosterone deprivation. Early testosterone replacement improves cardiac Ca2+transient regulation and contractility, suggesting the necessity of early intervention in conditions of testosterone-deprivation. 2018-09-05T03:28:44Z 2018-09-05T03:28:44Z 2017-11-01 Journal 15321991 01434160 2-s2.0-85027696915 10.1016/j.ceca.2017.08.003 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85027696915&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/56672
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Biochemistry, Genetics and Molecular Biology
spellingShingle Biochemistry, Genetics and Molecular Biology
Punate Weerateerangkul
Krekwit Shinlapawittayatorn
Siripong Palee
Nattayaporn Apaijai
Siriporn C. Chattipakorn
Nipon Chattipakorn
Early testosterone replacement attenuates intracellular calcium dyshomeostasis in the heart of testosterone-deprived male rats
description © 2017 Elsevier Ltd Background Testosterone deficiency in elderly men increases the risk of cardiovascular disease. In bilateral orchiectomized (ORX) animals, impaired cardiac Ca2+regulation was observed, and this impairment could be improved by testosterone replacement, indicating the important role of testosterone in cardiac Ca2+regulation. However, the temporal changes of Ca2+dyshomeostasis in testosterone-deprived conditions are unclear. Moreover, the effects of early vs. late testosterone replacement are unknown. We hypothesized that the longer the deprivation of testosterone, the greater the impairment of cardiac Ca2+homeostasis, and that early testosterone replacement can effectively reduce this adverse effect. Methods Male Wistar rats were randomly divided into twelve groups, four sets of three. The first set were ORX for 2, 4 and 8 weeks, the second set were sham-operated groups of the same periods, the third set were ORX for 8 weeks coupled with a subcutaneous injection of vehicle (control), testosterone during weeks 1–8 (early replacement) or testosterone during weeks 5–8 (late replacement), and finally the 12-week sham-operated, ORX and ORX treated with testosterone groups. Cardiac Ca2+transients (n = 4-5/group), L-type calcium current (ICa-L) (n = 4/group), Ca2+regulatory proteins (n = 6/group) and cardiac function (n = 5/group) were determined. Results In the ORX rats, impaired cardiac Ca2+transients and reduced ICa-Lwere observed initially 4 weeks after ORX as shown by decreased Ca2+transient amplitude, rising rate and maximum and average decay rates. No alteration of Ca2+regulatory proteins such as the L-type Ca2+channels, ryanodine receptor type 2, Na+-Ca2+exchangers and SERCA2a were observed. Early testosterone replacement markedly improved cardiac Ca2+transients, whereas late testosterone replacement did not. The cardiac contractility was also improved after early testosterone replacement. Conclusions Impaired cardiac Ca2+homeostasis is time-dependent after testosterone deprivation. Early testosterone replacement improves cardiac Ca2+transient regulation and contractility, suggesting the necessity of early intervention in conditions of testosterone-deprivation.
format Journal
author Punate Weerateerangkul
Krekwit Shinlapawittayatorn
Siripong Palee
Nattayaporn Apaijai
Siriporn C. Chattipakorn
Nipon Chattipakorn
author_facet Punate Weerateerangkul
Krekwit Shinlapawittayatorn
Siripong Palee
Nattayaporn Apaijai
Siriporn C. Chattipakorn
Nipon Chattipakorn
author_sort Punate Weerateerangkul
title Early testosterone replacement attenuates intracellular calcium dyshomeostasis in the heart of testosterone-deprived male rats
title_short Early testosterone replacement attenuates intracellular calcium dyshomeostasis in the heart of testosterone-deprived male rats
title_full Early testosterone replacement attenuates intracellular calcium dyshomeostasis in the heart of testosterone-deprived male rats
title_fullStr Early testosterone replacement attenuates intracellular calcium dyshomeostasis in the heart of testosterone-deprived male rats
title_full_unstemmed Early testosterone replacement attenuates intracellular calcium dyshomeostasis in the heart of testosterone-deprived male rats
title_sort early testosterone replacement attenuates intracellular calcium dyshomeostasis in the heart of testosterone-deprived male rats
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85027696915&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/56672
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