Crocetin attenuates DHT-induced polycystic ovary syndrome in mice via revising kisspeptin neurons
Crocetin attenuates DHT-induced polycystic ovary syndrome in mice via revising kisspeptin neurons
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藏红花酸通过修改 Kisspeptin 神经元减轻 DHT 诱导的小鼠多囊卵巢综合征
DOI：
10.1016/j.biopha.2018.08.135
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发表时间：
2018-11-01
影响因子：
7.5
通讯作者：
Sheng, Liang
中科院分区：
文献类型：
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作者：
Hu, Qiaoyun;Jin, Jing;Sheng, Liang
多囊卵巢综合征(PCOS)是育龄妇女最常见的内分泌疾病，表现为高雄激素血症和下丘脑-垂体-卵巢(HPO)轴紊乱，即下丘脑促性腺激素释放激素(GnRH)表达异常，血清黄体生成素(LH)/卵泡刺激素(FSH)水平升高。这种紊乱可能与下丘脑Kispeptin的表达密切相关，后者被认为是GnRH的关键调节因子。西红花素是藏红花的主要成分之一，临床用于妇科疾病的治疗，对产前暴露于双氢睾酮(DHT)所致的小鼠多囊卵巢综合征(PCOS)的治疗效果进行了评价。在这里，我们发现DHT处理的小鼠表现出与人类PCOS相似的表型，如卵巢更重，发情间期延长，卵泡多个增大，黄体较少，促黄体生成素和睾酮水平较高。Kispeptin在前腹侧脑室周围核(AVPV)表达较低，而在弓状核(ARC)表达较高。西红花酸治疗可防止动情间期延长和黄体减少，恢复孕酮(P4)、雌二醇(E_2)、睾酮(T)、促性腺激素释放激素(GnRH)、卵泡刺激素(FSH)、黄体生成素(L H)水平，提高动静脉曲张(AVPV)的Kispeptin水平，但降低ARC的Kispeptin水平。本研究提供了体内证据，表明西红花酸通过增加AVPV-Kisspeptin和降低ARC-Kisspeptin的表达来改善小鼠的多囊卵巢综合征。
Polycystic ovarian syndrome (PCOS), the most common endocrine disorder of women in reproductive age, is typical with hyperandrogenism and disturbance of the hypothalamus-pituitary-ovary (HPO) axis, i.e. abnormal expression of hypothalamic gonadotropin-releasing hormone (GnRH) followed by the elevated ratio of serum luteinizing hormone (LH) level to follicle-stimulating hormone (FSH) level. This derangement might have a close relationship with hypothalamic kisspeptin expression that is thought to be a key regulator of GnRH. Crocetin, one of the main components of Saffron clinically used as traditional medicine in gynecology diseases, was evaluated for its therapeutic effects on PCOS induced by prenatally exposure to dihydrotestosterone (DHT) in mice. Herein, we found that DHT-treated mice showed a similar phenotype to human PCOS such as heavier ovary, prolonged diestrus, multiple enlarged follicles with fewer corpus luteum, and higher LH and testosterone levels. Kisspeptin expression was lower in anteroventral periventricular nucleus (AVPV) but higher in arcuate nucleus (ARC). Treatment of crocetin prevented the prolongation of diestrus and reduction in corpora luteum, recover the levels of GnRH, FSH, LH, progesterone (P4), estradiol (E2) and testosterone (T), and increase the kisspeptin level in AVPV but reduce that in ARC. The present study provides in vivo evidence that crocetin improved the PCOS in mice via increasing AVPV-kisspeptin and reducing ARC-kisspeptin expression.