Punate Weerateerangkul1, Krekwit Shinlapawittayatorn2, Siripong Palee2, Nattayaporn Apaijai2, Siriporn C Chattipakorn3, Nipon Chattipakorn4. 1. Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand. 2. Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand. 3. Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand; Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, 50200, Thailand. 4. Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand. Electronic address: nchattip@gmail.com.
Abstract
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-L were 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.
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 ORXrats, impaired cardiac Ca2+ transients and reduced ICa-L were 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.
Authors: Elin Svedlund Eriksson; Inger Johansson; Anna K F Mårtensson; Marta Lantero Rodriguez; Maaike Schilperoort; Jan Kroon; Sander Kooijman; Elmir Omerovic; Linda Andersson; Malin C Levin; Patrick C N Rensen; Åsa Tivesten Journal: J Endocr Soc Date: 2022-09-01
Authors: Luis M Montaño; Bettina Sommer; Héctor Solís-Chagoyán; Bianca S Romero-Martínez; Arnoldo Aquino-Gálvez; Juan C Gomez-Verjan; Eduardo Calixto; Georgina González-Avila; Edgar Flores-Soto Journal: Int J Mol Sci Date: 2022-01-15 Impact factor: 5.923