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 Ca 2+ regulation was observed, and this impairment could be improved by testosterone replacement, indicating the important...

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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/6653943832/46337
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Institution: Chiang Mai University
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spelling th-cmuir.6653943832-463372018-04-25T07:36:05Z 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 Agricultural and Biological Sciences Arts and Humanities © 2017 Elsevier Ltd Background Testosterone deficiency in elderly men increases the risk of cardiovascular disease. In bilateral orchiectomized (ORX) animals, impaired cardiac Ca 2+ regulation was observed, and this impairment could be improved by testosterone replacement, indicating the important role of testosterone in cardiac Ca 2+ regulation. However, the temporal changes of Ca 2+ 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 Ca 2+ 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 Ca 2+ transients (n = 4-5/group), L-type calcium current (I Ca-L ) (n = 4/group), Ca 2+ regulatory proteins (n = 6/group) and cardiac function (n = 5/group) were determined. Results In the ORX rats, impaired cardiac Ca 2+ transients and reduced I Ca-L were observed initially 4 weeks after ORX as shown by decreased Ca 2+ transient amplitude, rising rate and maximum and average decay rates. No alteration of Ca 2+ regulatory proteins such as the L-type Ca 2+ channels, ryanodine receptor type 2, Na + -Ca 2+ exchangers and SERCA2a were observed. Early testosterone replacement markedly improved cardiac Ca 2+ transients, whereas late testosterone replacement did not. The cardiac contractility was also improved after early testosterone replacement. Conclusions Impaired cardiac Ca 2+ homeostasis is time-dependent after testosterone deprivation. Early testosterone replacement improves cardiac Ca 2+ transient regulation and contractility, suggesting the necessity of early intervention in conditions of testosterone-deprivation. 2018-04-25T06:53:05Z 2018-04-25T06:53:05Z 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/6653943832/46337
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Agricultural and Biological Sciences
Arts and Humanities
spellingShingle Agricultural and Biological Sciences
Arts and Humanities
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 Ca 2+ regulation was observed, and this impairment could be improved by testosterone replacement, indicating the important role of testosterone in cardiac Ca 2+ regulation. However, the temporal changes of Ca 2+ 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 Ca 2+ 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 Ca 2+ transients (n = 4-5/group), L-type calcium current (I Ca-L ) (n = 4/group), Ca 2+ regulatory proteins (n = 6/group) and cardiac function (n = 5/group) were determined. Results In the ORX rats, impaired cardiac Ca 2+ transients and reduced I Ca-L were observed initially 4 weeks after ORX as shown by decreased Ca 2+ transient amplitude, rising rate and maximum and average decay rates. No alteration of Ca 2+ regulatory proteins such as the L-type Ca 2+ channels, ryanodine receptor type 2, Na + -Ca 2+ exchangers and SERCA2a were observed. Early testosterone replacement markedly improved cardiac Ca 2+ transients, whereas late testosterone replacement did not. The cardiac contractility was also improved after early testosterone replacement. Conclusions Impaired cardiac Ca 2+ homeostasis is time-dependent after testosterone deprivation. Early testosterone replacement improves cardiac Ca 2+ 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/6653943832/46337
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