Developmental programming: insulin sensitizer treatment improves reproductive function in prenatal testosterone-treated female sheep.
Developmental programming: insulin sensitizer treatment improves reproductive function in prenatal testosterone-treated female sheep.
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DOI：
10.1210/en.2010-0124
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发表时间：
2010-08
期刊：
影响因子：
4.8
通讯作者：
A. Veiga-Lopez;James S. Lee;V. Padmanabhan
中科院分区：
文献类型：
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作者：
A. Veiga-Lopez;James S. Lee;V. Padmanabhan
产前睾酮(T)过量会导致生殖和代谢紊乱，包括胰岛素抵抗，这是多囊卵巢综合征女性的特征。这项研究测试了这样的假设，即胰岛素抵抗与产前接受T治疗的女性生殖障碍的严重程度有关。妊娠绵羊在妊娠30~90天每半周一次肌注丙酸三酯100 mg。在第一个繁殖季节结束后，立即给一组对照和产前T处理(TR)绵羊口服胰岛素增敏剂(罗格列酮，8 mg/d)，为期8个月。未处理的对照组和产前接受T处理的女性(T组)被平行研究。生化分析显示罗格列酮在绵羊身上使用是安全的。胰岛素增敏剂治疗前后的糖耐量试验发现，与T组相比，胰岛素增敏剂降低了约50%的累积胰岛素、累积胰岛素/葡萄糖比值和胰岛素曲线下面积，增加了约70%的胰岛素敏感指数。与第一个繁殖季节相比，20%的TR雌性在第二个繁殖季节表现出更少的周期数，相比之下，80%的T组雌性表现出这种恶化。胰岛素增敏剂治疗也减少了第二个繁殖季的异常周期数(<gt；/=18d)，与第一个相比，在第二个繁殖季，与T组雌性相比，第二个繁殖季的雌性出现了增加。这些发现提供了证据，证明胰岛素增敏剂治疗防止了产前T处理的绵羊生殖轴的进一步恶化，这一发现与患有多囊卵巢综合征的妇女具有翻译相关性。
Prenatal testosterone (T) excess causes reproductive and metabolic disruptions including insulin resistance, attributes of women with polycystic ovary syndrome. This study tested the hypothesis that insulin resistance contributes toward severity of reproductive disruptions in prenatally T-treated females. Pregnant sheep were injected im with 100 mg of T-propionate semiweekly from d 30-90 of gestation. Immediately after the first breeding season, a subset of controls and prenatal T-treated (TR) sheep were administered an insulin sensitizer (rosiglitazone; 8 mg/d) orally for 8 months. Untreated control and prenatal T-treated females (T group) were studied in parallel. Biochemical analyses revealed rosiglitazone to be safe for use in sheep. Glucose tolerance tests performed before and after the insulin sensitizer treatment found that insulin sensitizer decreased cumulative insulin, cumulative insulin/glucose ratio, and insulin area under the curve by about 50% and increased the insulin sensitivity index by about 70% in the TR compared with the T group. Twenty percent of TR females showed a reduced number of cycles in the second relative to first breeding season as opposed to 80% of T group females showing such deterioration. Insulin sensitizer treatment also decreased the number of aberrant cycles (>/=18 d) during the second breeding season in the TR group relative to the first as opposed to the T group females showing an increase in the second breeding season relative to the first. These findings provide evidence that insulin sensitizer treatment prevents further deterioration of the reproductive axis in prenatal T-treated sheep, a finding of translational relevance to women with polycystic ovary syndrome.