Alexanderson Camilla, Eriksson Elias, Stener-Victorin Elisabet, Lystig Theodore, Gabrielsson Britt, Lönn Malin, Holmäng Agneta
Institute of Neuroscience and Physiology, Department of Physiology/Endocrinology, Sahlgrenska Academy, Göteborg University, Box 434, 405 30, Göteborg, Sweden.
Endocrinology. 2007 Nov;148(11):5369-76. doi: 10.1210/en.2007-0305. Epub 2007 Jul 26.
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.
出生后的事件会导致成年期代谢综合征的特征。在本研究中，出生后给予睾酮会降低成年雌性大鼠的胰岛素敏感性，并增加肠系膜脂肪储存、肠系膜脂肪细胞大小、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程序化效应中的作用，我们将暴露于睾酮的大鼠与暴露于雌二醇或双氢睾酮（DHT）的大鼠进行了比较。经雌二醇处理的大鼠胰岛素敏感性低于经睾酮处理的大鼠，并且与那些大鼠一样，肠系膜脂肪细胞增大且甘油三酯水平升高。DHT也降低了胰岛素敏感性，但没有模拟睾酮的其他代谢效应。所有接受治疗的大鼠可能都无排卵，但只有接受睾酮治疗的大鼠睾酮水平降低。本研究证实了我们之前的发现，即出生后给予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DHT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程序化作用。因此，早年暴露于性激素等损伤可能会产生长期影响，从而导致成年期胰岛素敏感性、脂肪组织和脂质谱紊乱的易感性。
