LeRoith Derek
Mount Sinai School of Medicine, One Gustave L. Levy Place, Levy Place Box 1055, New York, NY 10029, USA.
Pediatr Endocrinol Rev. 2008 Feb;5 Suppl 2:739-43.
Since the original somatomedin hypothesis was first put forward, several major revisions have been made. These include the identification of the insulin-like growth factors (IGF-I and IGF-II) and, importantly, the finding that these substances have local (autocrine/paracrine) as well as endocrine effects. Differentiating the roles of IGF-I at these different levels has been an ongoing challenge. However, knowledge in this area has been advanced by studies of knockout mice with specific gene deletions of liver IGF-I as well as IGF binding proteins (IGFBPs). Targeting IGFBP and the acid-labile subunit, in gene deletion studies, has made it possible to almost completely eliminate circulating IGF-I. Finally, animal models looking at IGFBPs have begun to provide insights into the numerous and often surprising effects these proteins themselves have. Despite the advances in knowledge made through these animal models, our understanding of the IGF-I system is still incomplete.
自从最初的生长调节素假说首次提出以来，已经进行了几次重大修订。这些修订包括胰岛素样生长因子（IGF-I和IGF-II）的鉴定，重要的是，发现这些物质具有局部（自分泌/旁分泌）以及内分泌作用。区分IGF-I在这些不同水平上的作用一直是一项持续的挑战。然而，通过对肝脏IGF-I以及IGF结合蛋白（IGFBPs）特定基因缺失的敲除小鼠的研究，这一领域的知识得到了推进。在基因缺失研究中，针对IGFBP和酸不稳定亚基，几乎完全消除循环中的IGF-I成为可能。最后，研究IGFBPs的动物模型已开始为这些蛋白质本身具有的众多且常常令人惊讶的作用提供见解。尽管通过这些动物模型在知识方面取得了进展，但我们对IGF-I系统的理解仍然不完整。
