Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Cell Metab. 2011 Oct 5;14(4):453-65. doi: 10.1016/j.cmet.2011.08.009.
Estrogens regulate body weight and reproduction primarily through actions on estrogen receptor-α (ERα). However, ERα-expressing cells mediating these effects are not identified. We demonstrate that brain-specific deletion of ERα in female mice causes abdominal obesity stemming from both hyperphagia and hypometabolism. Hypometabolism and abdominal obesity, but not hyperphagia, are recapitulated in female mice lacking ERα in hypothalamic steroidogenic factor-1 (SF1) neurons. In contrast, deletion of ERα in hypothalamic pro-opiomelanocortin (POMC) neurons leads to hyperphagia, without directly influencing energy expenditure or fat distribution. Further, simultaneous deletion of ERα from both SF1 and POMC neurons causes hypometabolism, hyperphagia, and increased visceral adiposity. Additionally, female mice lacking ERα in SF1 neurons develop anovulation and infertility, while POMC-specific deletion of ERα inhibits negative feedback regulation of estrogens and impairs fertility in females. These results indicate that estrogens act on distinct hypothalamic ERα neurons to regulate different aspects of energy homeostasis and reproduction.
雌激素主要通过雌激素受体-α（ERα）作用来调节体重和生殖。然而，介导这些效应的 ERα 表达细胞尚未确定。我们证明，雌性小鼠大脑特异性 ERα 缺失会导致腹型肥胖，这源于摄食过度和代谢降低。在缺乏下丘脑类固醇生成因子-1（SF1）神经元 ERα 的雌性小鼠中，重现了代谢降低和腹型肥胖，但没有摄食过度。相比之下，下丘脑促黑激素原（POMC）神经元 ERα 的缺失会导致摄食过度，而不会直接影响能量消耗或脂肪分布。此外，SF1 和 POMC 神经元中 ERα 的同时缺失会导致代谢降低、摄食过度和内脏脂肪增加。此外，SF1 神经元中 ERα 缺失的雌性小鼠会出现排卵障碍和不孕，而 POMC 特异性 ERα 缺失会抑制雌激素的负反馈调节并损害雌性的生育能力。这些结果表明，雌激素作用于不同的下丘脑 ERα 神经元来调节能量平衡和生殖的不同方面。
