Amino acid-dependent activation of liver estrogen receptor alpha integrates metabolic and reproductive functions via IGF-1.
Fiche publication
Date publication
février 2011
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre
Tous les auteurs :
Della Torre S, Rando G, Meda C, Stell A, Chambon P, Krust A, Ibarra C, Magni P, Ciana P, Maggi A
Lien Pubmed
Résumé
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 (ERalpha) through an mTOR-dependent mechanism. As a result of ERalpha activation, hepatic IGF-1 mRNA and blood IGF-1 are increased. Conversely, calorie restriction or selective ablation of ERalpha 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.
Référence
Cell Metab. 2011 Feb 2;13(2):205-14.