Effects of testosterone on cardiomyocyte calcium homeostasis and contractile function in female rats.
The role of testosterone (T) in the regulation of cardiovascular function in females is not well understood. Our goal was to examine the effect of T on cardiomyocyte biology by measuring sarcomere shortening/relaxation and intracellular calcium cycling in adult female Sprague-Dawley rats. The rats were divided into the following four groups: (1) sham operated; (2) ovariectomized (OVX); (3) OVX plus T; and (4) OVX + T plus an aromatase inhibitor (AI). The final group was added to rule out effects from bioconversion of T to oestradiol. Sarcomere/calcium dynamics were measured after 4 weeks at 2 and 6 Hz, then at 6 Hz following exposure to 300 nm isoprenaline. Additionally, the acute (i.e. non-genomic) effects of T were evaluated in sham-operated and OVX + T + AI rats. There were no group differences, nor was there evidence for an effect of T on frequency or isoprenaline response. Additionally, there were no findings to indicate an acute, non-genomic T effect. Moreover, the relative α- and β-myosin heavy chain isoform complement was unchanged by OVX or T replacement. Our results argue against acute or chronic effects of T on cardiomyocyte shortening dynamics, calcium cycling or myosin heavy chain expression, arguing against any direct effect of T on cardiomyocyte function in adult females.
Department of Obstetrics and Gynecology, University of Vermont College of Medicine, Burlington, VT, USA.
Ronald D
RD
Beesley
Bradley M
BM
Palmer
Peter R
PR
Casson
Michael J
MJ
Toth
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005260:Female; D006706:Homeostasis / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012518:Sarcomeres / Q000187:drug effects / Q000502:physiology; D013739:Testosterone / Q000494:pharmacology*
D013739:Testosterone; D018995:Myosin Heavy Chains; D002118:Calcium