Kisspeptin expression is decreased in the arcuate nucleus of hypothyroid female rats with irregular estrus cycles

Kisspeptin expression is decreased in the arcuate nucleus of hypothyroid female rats with irregular estrus cycles
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DOI:
10.1016/j.neures.2016.11.005
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发表时间:
2017-04-01
影响因子:
2.9
通讯作者:
Ozawa, Hitoshi
Ozawa, Hitoshi
中科院分区:
医学4区
文献类型:
--
作者:
Tomori, Yuji;Takumi, Ken;Ozawa, Hitoshi

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甲状腺激素不足抑制促性腺激素释放,导致生殖功能失调,尽管这种促性腺激素分泌中断的确切机制尚不清楚。Kisspeptin是一种能强烈刺激促性腺激素分泌的神经肽,在生殖功能中起重要作用。为了研究kisspeptin在甲状腺功能减退症促性腺激素分泌失调中的作用,我们研究了丙基硫氧嘧啶(PTU)处理的雌性大鼠下丘脑中Kiss mRNA表达和kisspeptin免疫反应性。在PTU处理的大鼠,血清甲状腺素(T4)显着降低,而促甲状腺激素(TSH)水平显着增加。此外,在PTU处理的大鼠中观察到不规则的发情周期。原位杂交和免疫组织化学显示,PTU处理的大鼠弓状核(ARC)中Kiss/mRNA表达神经元和Kisspeptin免疫反应阳性神经元的数量显著减少,但在前腹侧室周核(AVPV)中没有。虽然血清促黄体生成素(LH)和雌二醇(E2)水平不受影响,血清催乳素水平显着增加后PTU治疗。这些数据表明,kisspeptin在ARC中的表达被抑制甲状腺激素不足,这表明在甲状腺功能减退症的生殖功能失调是由kisspeptin神经元在ARC中的抑制。(C)2016爱思唯尔爱尔兰有限公司和日本神经科学学会。All rights reserved.
Insufficiency of thyroid hormones inhibits gonadotropin release and results in dysregulation of reproductive function, although the precise mechanism of this disrupted gonadotropin secretion remains unclear. Kisspeptin is a neuropeptide that strongly stimulates gonadotropin secretion and plays an important role in reproductive function. To examine the involvement of kisspeptin in the dysregulation of gonadotropin secretion in hypothyroidism, we investigated Kiss] mRNA expression and kisspeptin immunoreactivity in the hypothalamus of female rats treated with propylthiouracil (PTU). In the PTU-treated rats, serum thyroxine (T4) was significantly decreased, whereas thyroid stimulating hormone (TSH) levels were significantly increased. In addition, irregular estrus cycles were observed in PTU-treated rats. In situ hybridization and immunohistochemistry revealed significant reductions in the number of Kiss/mRNAexpressing neurons and kisspeptin-immunoreactive neurons in the arcuate nucleus (ARC) but not in the anteroventral periventricular nucleus (AVPV) of the PTU-treated rats. Although the serum levels of luteinizing hormone (LH) and estradiol (E2) were unaffected, serum prolactin levels were significantly increased after PTU treatment. These data indicate that kisspeptin expression in the ARC is suppressed under thyroid hormone insufficiency, suggesting that the dysregulation of reproductive function in hypothyroidism is caused by inhibition of kisspeptin neurons in the ARC. (C) 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.