Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Bari, Italy.
Department of Physiology and Pharmacology 'V. Erspamer', SAPIENZA University, Rome, Italy.
J Endocrinol. 2021 May;249(2):135-148. doi: 10.1530/JOE-20-0346.
We explored the involvement of oxytocin receptor (Oxtr)/transient-receptor-potential-vanilloid-1 (TRPV1) genes and oxytocin (Oxt) on the adaptation of skeletal muscle to cold stress challenge in mice. Oxtr expression in hypothalamic paraventricular (PVN), supraoptic nuclei (SON), and hippocampus (HIPP) were evaluated by immunohistochemistry in parallel with the measurement of circulating Oxt. The Oxtr and TRPV1 gene expressions in soleus (SOL) and tibialis anterior (TA) muscles were investigated by RT-PCR. Histological studies of the cardiac muscle after cold stress were also performed. Male mice (n = 15) were divided into controls maintained at room temperature (RT = 24°C), exposed to cold stress (CS) at T = 4°C for 6 h , and 5 days. Immunohistochemical studies showed that Oxtr protein expression increased by two-fold (P = 0.01) in PVN and by 1.5-fold (P = 0.0001) in HIPP after 6 h- and 5 days of CS but decreased by 2-fold (P = 0.026) in SON in 5 days. Both Oxtr and TRPV1 gene expression increased after 6 h and 5 days of CS in SOL and TA muscles. Oxtr vs TRPV1 gene expression in SOL and TA muscles evaluated by regression analysis was linearly correlated following CS at 6 h and 5 days but not at control temperature of 24 ± 1°C, supporting the hypothesis of coupling between these genes. The circulating levels of Oxt are unaffected after 6 h of CS but decreased by 0.2-fold (P = 0.0141) after 5 days-CS. This is the first report that Oxtr and TRPV1 expressions are upregulated in response to cold acclimation in skeletal muscle. The up-regulation of Oxtr in PVN and HIPP balances the decrease of circulating Oxt.
我们探讨了催产素受体(Oxtr)/瞬时受体电位香草酸 1 型(TRPV1)基因和催产素(Oxt)在小鼠骨骼肌适应冷应激挑战中的作用。通过免疫组织化学平行评估下丘脑室旁核(PVN)、视上核(SON)和海马(HIPP)中的 Oxtr 表达,并测量循环 Oxt。通过 RT-PCR 研究比目鱼肌(SOL)和胫骨前肌(TA)肌肉中的 Oxtr 和 TRPV1 基因表达。还对冷应激后的心肌进行了组织学研究。雄性小鼠(n = 15)分为三组:对照组在室温(RT = 24°C)下维持,冷应激组(CS)在 T = 4°C 下暴露 6 h 和 5 天。免疫组织化学研究表明,6 h 和 5 天 CS 后,PVN 中的 Oxtr 蛋白表达增加了两倍(P = 0.01),HIPP 中增加了 1.5 倍(P = 0.0001),但 5 天后 SON 中减少了 2 倍(P = 0.026)。6 h 和 5 天 CS 后,SOL 和 TA 肌肉中的 Oxtr 和 TRPV1 基因表达均增加。CS 后 6 h 和 5 天时,SOL 和 TA 肌肉中的 Oxtr 与 TRPV1 基因表达通过回归分析呈线性相关,但在 24 ± 1°C 的对照温度下无相关性,这支持了这两个基因之间存在耦合的假说。6 h CS 后循环 Oxt 水平不受影响,但 5 天 CS 后降低 0.2 倍(P = 0.0141)。这是第一个报道 Oxtr 和 TRPV1 表达在骨骼肌对冷适应的反应中上调的报告。PVN 和 HIPP 中 Oxtr 的上调平衡了循环 Oxt 的减少。