Postnatal testosterone exposure results in insulin resistance, enlarged mesenteric adipocytes, and an atherogenic lipid profile in adult female rats:: Comparisons with estradiol and dihydrotestosterone

被引:58
作者
Alexanderson, Camilla
Eriksson, Elias
Stener-Victorin, Elisabet
Lystig, Theodore
Gabrielsson, Britt
Loenn, Malin
Holmaeng, Agneta
机构
[1] Gothenburg Univ, Dept Physiol, Inst Neurosci & Physiol, Sahlgrenska Acad, S-40530 Gothenburg, Sweden
[2] Gothenburg Univ, Dept Pharmacol, Inst Neurosci & Physiol, Sahlgrenska Acad, S-40530 Gothenburg, Sweden
[3] Gothenburg Univ, Inst Med, Dept Mol & Clin Med, Sahlgrenska Acad, S-40530 Gothenburg, Sweden
关键词
D O I
10.1210/en.2007-0305
中图分类号
R5 [内科学];
学科分类号
1002 [临床医学]; 100201 [内科学];
摘要
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.
引用
收藏
页码:5369 / 5376
页数:8
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