Cintron-Colon Rigo, Shankar Kokila, Sanchez-Alavez Manuel, Conti Bruno
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Facultad de Medicina y Psicología, Universidad Autónoma de Baja California, Tijuana, México.
Temperature (Austin). 2019 Apr 26;6(2):158-168. doi: 10.1080/23328940.2019.1607653. eCollection 2019.
During calorie restriction (CR), endotherms adjust several physiological processes including the decrease of core body temperature (T) and reduction of energy expenditure. We recently found that CR-induced hypothermia is regulated in a sex-dependent manner in mice with lowered central insulin-like growth factor receptor signaling. Here, we describe the contribution of sex hormones to CR-induced hypothermia in wild type C57BL6 mice by measuring T of female and male mice following bilateral gonadectomy and hormonal replacement. Specifically, we evaluated the effects of progesterone (P4), 17-ß estradiol (E2), a combination of both (P4 + E2) in females and of 5-α dihydrotestosterone (5-α DHT) in males. Gonadectomy resulted in an earlier and stronger CR-induced hypothermia in both sexes. These effects were fully antagonized in females by E2 replacement, but not by P4, which had only minor and partial effects when used alone and did not prevent the action of E2 during CR when both hormones were given in combination. 5-α-DHT had only minor and transient effects on preventing the reduction of T during CR on gonadectomized male mice. These findings indicate that gonadal hormones contribute to sex-specific regulation of T and energy expenditure when nutrient availability is scarce. : AL: ad libitum; ANOVA: analysis of variance; CR: calorie restriction; E2: 17-ß estradiol; GNX: gonadectomy or gonadectomized; IGF-1R: insulin-like growth factor 1 receptor; POA: preoptic area; P4: progesterone; RM: repeated measures; SD: standard deviation; SEM: standard error of mean; T: core body temperature; WT: wildtype; 5-α DHT: 5-α dihydrotestosterone.
在热量限制(CR)期间,恒温动物会调整多种生理过程,包括降低核心体温(T)和减少能量消耗。我们最近发现,在中枢胰岛素样生长因子受体信号降低的小鼠中,CR诱导的体温过低是以性别依赖的方式调节的。在这里,我们通过测量双侧性腺切除和激素替代后雌性和雄性小鼠的T,描述了性激素对野生型C57BL6小鼠CR诱导的体温过低的作用。具体来说,我们评估了孕酮(P4)、17-β雌二醇(E2)、两者的组合(P4 + E2)对雌性小鼠的影响,以及5-α双氢睾酮(5-α DHT)对雄性小鼠的影响。性腺切除导致两性中CR诱导的体温过低出现得更早且更强烈。在雌性小鼠中,E2替代完全拮抗了这些影响,但P4没有,P4单独使用时只有轻微和部分影响,并且在两种激素联合使用时,P4并不能阻止CR期间E2的作用。5-α-DHT对防止性腺切除的雄性小鼠在CR期间T的降低只有轻微和短暂的影响。这些发现表明,当营养供应不足时,性腺激素有助于对T和能量消耗进行性别特异性调节。:AL:随意进食;ANOVA:方差分析;CR:热量限制;E2:17-β雌二醇;GNX:性腺切除或去势;IGF-1R:胰岛素样生长因子1受体;POA:视前区;P4:孕酮;RM:重复测量;SD:标准差;SEM:平均标准误差;T:核心体温;WT:野生型;5-α DHT:5-α双氢睾酮