Estradiol Priming Improves Gonadotrope Sensitivity and Pro-Inflammatory Cytokines in Obese Women
Estradiol Priming Improves Gonadotrope Sensitivity and Pro-Inflammatory Cytokines in Obese Women
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DOI：
10.1210/jc.2015-1946
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发表时间：
2015-11-01
影响因子：
5.8
通讯作者：
Polotsky, Alex J.
中科院分区：
文献类型：
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作者：
Al-Safi, Zain A.;Liu, Huayu;Polotsky, Alex J.
背景：肥胖与促炎状态和相对低促性腺激素性性腺功能减退有关。雌激素（E2）是这些现象之间的潜在联系，因为它对促性腺激素分泌表现出负反馈，并且还抑制促炎细胞因子的产生。目的：我们试图检查雌激素启动对下丘脑-垂体-卵巢轴的影响肥胖。设计、设置和参与者：这是一项在一个学术中心进行的干预性研究，研究对象为11名肥胖女性和10名正常体重（NW）女性。在给予经皮雌二醇0.1 mg/kg之前和之后，进行频繁的血液采样研究和一个月的每日尿液收集。结果：E2增加了肥胖妇女LH脉冲幅度和FSH对GnRH的反应（分别为P = 0.048和P <0.03），但对NW妇女无影响。在E2激发后，排卵肥胖但非NW妇女的黄体孕酮增加25%（P = 0.01）。肥胖女性的基线IL-6、IL-10、TGF-β和IL-12显著高于NW（所有P < .05）; E2后这些水平降低（IL-1 β为-6%，IL-8为-21%，TGF-β为-5%，IL-12为-5%;所有P <0.05），但NW女性中没有。E2预充似乎可以改善有排卵的肥胖妇女的下丘脑-垂体-卵巢轴功能和全身炎症。减少垂体水平的慢性炎症可能会减少肥胖对生育的负担。
Context: Obesity is associated with a pro-inflammatory state and relative hypogonadotropic hypogonadism. Estrogen (E2) is a potential link between these phenomena because it exhibits negative feedback on gonadotropin secretion and also inhibits production of pro-inflammatory cytokines.Objective: We sought to examine the effect of estrogen priming on the hypothalamic-pituitary-ovarian axis in obesity.Design, Setting, and Participants: This was an interventional study at an academic center of 11 obese and 10 normal-weight (NW) women.Intervention: A frequent blood-sampling study and one month of daily urinary collection were performed before and after administration of transdermal estradiol 0.1 mg/d for one entire menstrual cycle.Main Outcome Measures: Serum LH and FSH before and after GnRH stimulation, and urinary estrogen and progesterone metabolites were measured.Results: E2 increased LH pulse amplitude and FSH response to GnRH (P = .048, and P < .03, respectively) in obese but not NW women. After E2 priming, ovulatory obese but not NW women had a 25% increase in luteal progesterone (P = .01). Obese women had significantly higher baseline IL-6, IL-10, TGF-beta, and IL-12 compared with NW (all P < .05); these levels were reduced after E2 (-6% for IL-1 beta, -21% for IL-8, -5% for TGF-beta, -5% for IL-12; all P < .05) in obese but not in NW women.Conclusions: E2 priming seems to improve hypothalamic-pituitary-ovarian axis function and systemic inflammation in ovulatory, obese women. Reducing chronic inflammation at the pituitary level may decrease the burden of obesity on fertility.