Effects of thyroxine on expression of proteins related to thyroid hormone functions (TR-α, TR-β, RXR and ERK1/2) in uterus during peri-implantation period
Effects of thyroxine on expression of proteins related to thyroid hormone functions (TR-α, TR-β, RXR and ERK1/2) in uterus during peri-implantation period
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DOI：
10.1016/j.biopha.2017.11.128
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发表时间：
2017-12-01
影响因子：
7.5
通讯作者：
Salleh, Naguib
中科院分区：
文献类型：
--
作者：
Sayem, Abu Sadat Md;Giribabu, Nelli;Salleh, Naguib
前言：甲状腺激素在胚胎着床过程中发挥着重要作用，但其在围着床期子宫内的作用机制尚不完全清楚。在这项研究中，我们假设甲状腺激素可以影响与其功能相关的蛋白质的表达，这可能解释了甲状腺激素在这一时期在子宫内的作用机制。方法：雌性大鼠口服他巴唑(0.03%饮用水中的0.03%)21天后，与甲状腺功能正常的雄性大鼠按1：1的比例交配。通过阴道塞子的存在确认怀孕，并将这一天指定为第一天。然后给妊娠甲减雌性大鼠皮下注射甲状腺素(20、40和80 mg/kg/d)，连续3天。最后一次注射(妊娠第4天)后1天处死雌性大鼠，用Western blotting法检测子宫中甲状腺激素受体(TR-α和β)、类维A酸X受体(RXR)和细胞外信号调节激酶(ERK1/2)的表达，免疫荧光法观察其在子宫内膜中的分布。结果：随着甲状腺素剂量的增加，Trα-1、Trp-β-1和ERK1/2蛋白在子宫中的表达增加，而RXR的表达无明显变化。结论：甲状腺功能减退妊娠大鼠妊娠4天时，甲状腺激素诱导的妊娠大鼠子宫组织中的转录因子受体α-1、受体β-1和ERK1/2的表达增加，提示甲状腺激素可能通过上调这些蛋白的表达来调节胚胎着床前子宫的变化。
Introduction: Thyroid hormone is known to play important role during embryo implantation, however mechanisms underlying its actions in uterus during peri-implantation period has not been fully identified. In this study, we hypothesized that thyroid hormone could affect expression of proteins related to its function, where these could explain mechanisms for its action in uterus during this period.Methods: Female rats, once rendered hypothyroid via oral administration of methimazole (0.03% in drinking water) for twenty-one days were mated with fertile euthyroid male rats at 1: 1 ratio. Pregnancy was confirmed by the presence of vaginal plug and this was designated as day-1. Thyroxine (20, 40 and 80 mu g/kg/day) was then subcutaneously administered to pregnant, hypothyroid female rats for three days. A day after last injection (day four pregnancy), female rats were sacrificed and expression of thyroid hormone receptors (TR-alpha and beta), retinoid X receptor (RXR) and extracellular signal-regulated kinase (ERK1/2) in uterus were quantified by Western blotting while their distribution in endometrium was visualized by immunofluorescence.Results: Expression of TR alpha-1, TR beta-1 and ERK1/2 proteins in uterus increased with increasing doses of thyroxine however no changes in RXR expression was observed. These proteins were found in the stroma with their distribution levels were relatively higher following thyroxine treatment.Conclusions: Increased expression of TR alpha-1, TR beta-1 and ERK1/2 at day 4 pregnancy in thyroxine-treated hypothyroid pregnant rats indicate the importance of thyroxine in up-regulating expression of these proteins that could help mediate the uterine changes prior to embryo implantation.