Center of Excellence on Neurodegenerative Diseases, University of Milan, Milan, 20133, Italy.
Cell Metab. 2011 Feb 2;13(2):205-14. doi: 10.1016/j.cmet.2011.01.002.
Throughout evolution, organisms have devised strategies to limit fertility in case of prolonged starvation. In mammals, the liver plays a central role in the orchestration of mechanisms allowing for the maintenance of energy homeostasis. We here demonstrate that dietary amino acids regulate the transcriptional activity of hepatic estrogen receptor alpha (ERα) through an mTOR-dependent mechanism. As a result of ERα activation, hepatic IGF-1 mRNA and blood IGF-1 are increased. Conversely, calorie restriction or selective ablation of ERα in the liver decrease blood IGF-1 to levels inadequate for the correct proliferation of the lumen epithelium in the uterus and the progression of the estrous cycle. We propose that the liver acts as critical mediator of energetic and reproductive functions responsible for the blockade of the estrous cycle in case of protein scarcity. Our findings may provide novel insights to understand the cause of selected forms of infertility and metabolic alterations in women after menopause.
在进化过程中，生物体设计了各种策略来限制生育能力，以防长期饥饿。在哺乳动物中，肝脏在协调允许维持能量稳态的机制方面发挥着核心作用。我们在这里证明，膳食氨基酸通过 mTOR 依赖性机制调节肝雌激素受体 alpha（ERα）的转录活性。由于 ERα 的激活，肝 IGF-1 mRNA 和血液 IGF-1 增加。相反，热量限制或选择性敲除肝脏中的 ERα 会降低血液 IGF-1 至不足以正确增殖子宫腔上皮和发情周期进展的水平。我们提出，肝脏作为能量和生殖功能的关键调节者，负责在蛋白质匮乏时阻断发情周期。我们的发现可能为理解绝经后女性某些形式的不孕和代谢改变的原因提供新的见解。
