Testosterone mediates hyperthermic response of mice to heat exposure

Testosterone mediates hyperthermic response of mice to heat exposure
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DOI:
10.1016/j.lfs.2018.10.058
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发表时间:
2018-12-01
期刊:
影响因子:
6.1
通讯作者:
Yu, Tianzheng
Yu, Tianzheng
中科院分区:
医学2区
文献类型:
--
作者:
Chen, Yifan;Yu, Tianzheng

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目的:替吉奥被认为是热诱导损伤的潜在促成因素。主要方法:成年C57 BL/6 J雄性小鼠行性腺切除术或假手术,随后分别植入Gnx或睾酮(Gnx + T)。在急性热暴露期间遥测小鼠的体核心温度(Tc)。热暴露的热反应也检查了年龄匹配的雌性小鼠在每个阶段的动情周期。关键发现:基础Tc低于假雄性小鼠比女性,但假,Gnx或Gnx +T男性之间没有差异。与假手术雄性小鼠相比,Gnx或Gnx +T小鼠腓肠肌中解偶联蛋白2和3的表达没有变化。在热暴露期间,与雌性相比,假手术雄性小鼠的Tc升高更快更大。Gnx雄性动物对热的快速高热反应被消除,但Gnx + T雄性动物未被消除。在接受低剂量或高剂量睾酮治疗的Gnx +T雄性动物中,Tc峰值与血浆睾酮浓度之间无显著相关性。在雌性小鼠中未检测到动情周期阶段对热暴露的热反应的影响。意义:我们发现雄性小鼠比雌性小鼠更容易出现热诱导的体温过高,这是通过阉割而不是通过阉割来预防的睾酮替代。这些结果表明,睾酮介导的热诱导的体温过高,是一个热应激的易感因素。
Aims: Testosterone is implicated as a potential contributing factor to heat-induced injury. We examined effects of testosterone on thermal response of mice to heat exposure.Main methods: Adult C57BL/6J male mice received gonadectomy or sham surgery subsequent vehicle (Gnx) or testosterone implants (Gnx + T). Body core temperature (Tc) of mice was recorded telemetrically during acute heat exposure. Thermal responses to heat exposure were also examined in age-matched female mice at each stage of the estrous cycle.Key findings: Basal Tc was lower in sham male mice than females, but did not differ among sham, Gnx or Gnx +T males. No alterations in expression of uncoupling proteins 2 and 3 in the gastrocnemius muscle were found in either Gnx or Gnx +T mice compared to sham males. During heat exposure, sham male mice had a faster and greater rise in Tc, compared to females. This rapid hyperthermic response to heat was abolished in Gnx males, but not in Gnx + T males. No significant correlation was revealed between peak Tc values and plasma testosterone concentrations in Gnx +T males treated with either low- or high-dose testosterone. No effects of estrous cycle phase on the thermal response to heat exposure were detected in female mice.Significance: We found that male mice were more susceptible to development of heat-induced hyperthermia than females and this was prevented by castration, not by castration with testosterone replacement. These results suggest that testosterone mediates heat-induced hyperthermia and is a heat stress susceptibility factor.