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睾酮介导小鼠对热暴露的发热反应。

Testosterone mediates hyperthermic response of mice to heat exposure.

机构信息

Department of Military and Emergency Medicine, Uniformed Services University Bethesda, MD 20814, USA.

Department of Military and Emergency Medicine, Uniformed Services University Bethesda, MD 20814, USA.

出版信息

Life Sci. 2018 Dec 1;214:34-40. doi: 10.1016/j.lfs.2018.10.058. Epub 2018 Oct 26.

DOI:10.1016/j.lfs.2018.10.058
PMID:30449451
Abstract

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.

摘要

目的

睾酮被认为是导致热应激损伤的潜在因素之一。本研究旨在探讨睾酮对雄性小鼠热暴露时热反应的影响。

方法

成年 C57BL/6J 雄性小鼠接受去势或假手术,随后给予载体(Gnx)或睾酮植入物(Gnx+T)。通过遥测法记录小鼠急性热暴露时的核心体温(Tc)。在每个动情周期阶段,还检查了年龄匹配的雌性小鼠对热暴露的热反应。

主要发现

与雌性小鼠相比,假手术雄性小鼠的基础 Tc 较低,但与去势或 Gnx+T 雄性小鼠相比无差异。与假手术雄性小鼠相比,Gnx 或 Gnx+T 小鼠的比目鱼肌中解偶联蛋白 2 和 3 的表达没有改变。与雌性小鼠相比,假手术雄性小鼠在热暴露时 Tc 上升更快、幅度更大。Gnx 雄性小鼠的这种快速高热反应被消除,但 Gnx+T 雄性小鼠未被消除。在给予低剂量或高剂量睾酮的 Gnx+T 雄性小鼠中,未发现峰值 Tc 值与血浆睾酮浓度之间存在显著相关性。在雌性小鼠中,未检测到动情周期阶段对热暴露时热反应的影响。

意义

我们发现雄性小鼠比雌性小鼠更容易发生热诱导性高热,去势可预防这种情况,而用睾酮替代则不能预防。这些结果表明,睾酮介导了热诱导性高热,是热应激易感性因素。

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