Regulation of HOXA-10 expression by testosterone in vitro and in the endometrium of patients with polycystic ovary syndrome
Regulation of HOXA-10 expression by testosterone in vitro and in the endometrium of patients with polycystic ovary syndrome
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DOI：
10.1210/jc.2002-021072
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发表时间：
2003-01-01
影响因子：
5.8
通讯作者：
Taylor, HS
中科院分区：
文献类型：
--
作者：
Cermik, D;Selam, B;Taylor, HS
多囊卵巢综合征（PCOS）影响约5%的育龄妇女，其特征是无排卵和雄激素分泌增加。尽管有能力纠正排卵障碍，但怀孕率仍然自相矛盾地低，而自然流产率很高。为了确定子宫功能障碍是否导致了多囊卵巢综合征的不良生殖结果，我们评估了卵巢雄激素增加对子宫内膜容受性必需基因的影响。子宫内膜中HOXA10的上调是胚胎着床的接受性所必需的。在体外，睾酮可抑制HOXA10的表达，而脱氢表雄酮、硫酸脱氢表雄酮或胰岛素均不能抑制HOXA10的表达。睾酮也可以阻止HOXA10表达的增加，这是之前用雌二醇或黄体酮报道的。双氢睾酮产生的效果与睾酮相似，而氟他胺阻断了睾酮的作用。多囊卵巢综合征患者的子宫内膜活检显示HOXA10 mRNA减少。睾酮是一种新的HOXA10调节因子。子宫HOXA10表达减少可能导致多囊卵巢综合征女性生殖潜力下降。
Polycystic ovary syndrome (PCOS) affects approximately 5% of reproductive-age women and is characterized by anovulation and increased androgen production. Despite the ability to correct ovulatory disorders, pregnancy rates remain paradoxically low, and spontaneous pregnancy loss rates are high. To determine whether uterine dysfunction contributed to the adverse reproductive outcomes in PCOS, we assessed the effect of the increased ovarian androgens on a well characterized gene essential to endometrial receptivity. Upregulation of HOXA10 in the endometrium is necessary for receptivity to embryo implantation. In vitro, HOXA10 expression was repressed by testosterone but not by dehydro-epiandrosterone, dehydroepiandrosterone sulfate, or insulin. Testosterone also prevented the increased expression of HOXA10 previously reported with estradiol or progesterone. Dihydrotestosterone produced an effect similar to that of testosterone, whereas flutamide blocked the testosterone effect. Endometrial biopsies, obtained from women with PCOS, demonstrated decreased HOXA10 mRNA. Testosterone is a novel regulator of HOXA10. Diminished uterine HOXA10 expression may contribute to the diminished reproduction potential of women with PCOS.