内分泌系统The endocrine system教学课件.ppt

FGF23和磷代谢 衰老基因Klotho的组织表达 Makoto Kuro-o。Nature 390, 45-51 (6 November 1997) Klotho基因敲除显示早老表型 Klotho基因敲除显示早老组织学表型 FGF23、Klotho和钙磷代谢及衰老 Altered mineralization in bone and kidney of Fgf23 knockout (Fgf23–/–) mice FGF23–FGFR/Klotho interactions * * The reason that PGE2 can exert such a wide variety of physiological effects is in part explained by the existence of at least 4 E-Prostanoid receptors, termed EP1, EP2, EP3, and EP4. Each subtype couples to a G-protein to initiate several intracellular signaling cascades upon ligand binding. Stimulation of the EP1 or EP3 receptors in the vasculature or in smooth muscle cells is thought to be vasoconstrictive. While activation of the EP2 or EP4 receptors is thought to promote vasodilatation. One can therefore imagine that the EP receptor expression profile of any given cell type or tissue will have a significant influence over the cellular response initiated by PGE2. However the absolute designation of the various roles for each of the receptor subtypes remains incomplete. . * Elucidating the role of the EP4 receptor in vivo has been hampered by the lack of EP4 receptor specific antagonists. Furthermore, conventional global gene targeting, and disruption of the EP4 receptor, causes perinatal death due to persistent patent ductus arteriosus. EP4 knockout survival rates reported by two different groups is less than 1% as reported by Dr. Bev Koller’s group at the university of North Carolina and Dr. Ichikawa’s group in Japan. To circumvent these difficulties and dissect the specific physiologic role of the EP4 receptor in the collecting duct, we utilized conditional gene targeting via the Cre-Lox system. * Recently, a hormone activated nuclear receptor called peroxisome-proliferator-activated receptor g (PPARg) has been identified. Similar to other nuclear hormone receptor, PPARg also contains several important domains including DNA binding domain, ligand binding domain, and AF2 domain. In presence of its spec