Postnatal testosterone exposure results in insulin resistance, enlarged mesenteric adipocytes, and an atherogenic lipid profile in adult female rats:: Comparisons with estradiol and dihydrotestosterone
Postnatal testosterone exposure results in insulin resistance, enlarged mesenteric adipocytes, and an atherogenic lipid profile in adult female rats:: Comparisons with estradiol and dihydrotestosterone
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DOI：
10.1210/en.2007-0305
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发表时间：
2007-11-01
期刊：
影响因子：
4.8
通讯作者：
Holmaeng, Agneta
中科院分区：
文献类型：
--
作者：
Alexanderson, Camilla;Eriksson, Elias;Holmaeng, Agneta
产后事件会导致成年期代谢综合征的特征。在这项研究中，出生后施用睾酮降低了成年雌性大鼠的胰岛素敏感性，增加了肠系膜脂肪库、肠系膜脂肪细胞的大小、总胆固醇、低密度脂蛋白胆固醇和甘油三酯的血清水平以及动脉粥样硬化指数。为了评估雌激素和雄激素受体在这些编程效应中的作用，我们将暴露于睾酮的大鼠与暴露于雌二醇或二氢睾酮（DHT）的大鼠进行了比较。雌二醇治疗的大鼠的胰岛素敏感性比睾酮治疗的大鼠低，并且与那些大鼠一样，肠系膜脂肪细胞增大，甘油三酯水平升高。 DHT 也会降低胰岛素敏感性，但不会模仿睾酮的其他代谢作用。所有接受治疗的大鼠都可能无排卵，但只有那些接受睾酮治疗的大鼠睾酮水平降低。这项研究证实了我们之前的发现，即出生后施用睾酮会降低成年雌性大鼠的胰岛素敏感性，并表明这种效应伴随着肠系膜脂肪组织和血清脂质水平的不利变化。雌二醇和双氢睾酮组的研究结果表明，雌激素受体比雄激素受体发挥更强的代谢编程效应。因此，生命早期接触性激素等伤害可能会产生长期影响，从而导致成年后胰岛素敏感性、脂肪组织和血脂状况容易受到干扰。
Postnatal events contribute to features of the metabolic syndrome in adulthood. In this study, postnatally administered testosterone reduced insulin sensitivity and increased the mesenteric fat depot, the size of mesenteric adipocytes, serum levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides, and the atherogenic index in adult female rats. To assess the involvement of estrogen and androgen receptors in these programming effects, we compared testosterone-exposed rats to rats exposed to estradiol or dihydrotestosterone (DHT). Estradiol-treated rats had lower insulin sensitivity than testosterone-treated rats and, like those rats, had enlarged mesenteric adipocytes and increased triglyceride levels. DHT also reduced insulin sensitivity but did not mimic the other metabolic effects of testosterone. All treated rats were probably anovulatory, but only those treated with testosterone had reduced testosterone levels. This study confirms our previous finding that postnatal administration of testosterone reduces insulin sensitivity in adult female rats and shows that this effect is accompanied by unfavorable changes in mesenteric fat tissue and in serum lipid levels. The findings in the estradiol and DHT groups suggest that estrogen receptors exert stronger metabolic programming effects than androgen receptors. Thus, insults such as sex hormone exposure in early life may have long-lasting effects, thereby creating a predisposition to disturbances in insulin sensitivity, adipose tissue, and lipid profile in adulthood.