University of Sydney, Kolling Institute, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
Nat Rev Endocrinol. 2024 Jul;20(7):414-425. doi: 10.1038/s41574-024-00970-4. Epub 2024 Mar 21.
The acid-labile subunit (ALS) of the insulin-like growth factor (IGF) binding protein (IGFBP) complex, encoded in humans by IGFALS, has a vital role in regulating the endocrine transport and bioavailability of IGF-1 and IGF-2. Accordingly, ALS has a considerable influence on postnatal growth and metabolism. ALS is a leucine-rich glycoprotein that forms high-affinity ternary complexes with IGFBP-3 or IGFBP-5 when they are occupied by either IGF-1 or IGF-2. These complexes constitute a stable reservoir of circulating IGFs, blocking the potentially hypoglycaemic activity of unbound IGFs. ALS is primarily synthesized by hepatocytes and its expression is lower in non-hepatic tissues. ALS synthesis is strongly induced by growth hormone and suppressed by IL-1β, thus potentially serving as a marker of growth hormone secretion and/or activity and of inflammation. IGFALS mutations in humans and Igfals deletion in mice cause modest growth retardation and pubertal delay, accompanied by decreased osteogenesis and enhanced adipogenesis. In hepatocellular carcinoma, IGFALS is described as a tumour suppressor; however, its contribution to other cancers is not well delineated. This Review addresses the endocrine physiology and pathology of ALS, discusses the latest cell and proteomic studies that suggest emerging cellular roles for ALS and outlines its involvement in other disease states.
胰岛素样生长因子（IGF）结合蛋白（IGFBP）复合物的酸不稳定亚基（ALS），在人类中由 IGFALS 编码，在调节 IGF-1 和 IGF-2 的内分泌运输和生物利用度方面起着至关重要的作用。因此，ALS 对出生后的生长和代谢有很大的影响。ALS 是一种富含亮氨酸的糖蛋白，当它与 IGFBP-3 或 IGFBP-5 结合时，会形成与 IGF-1 或 IGF-2 具有高亲和力的三元复合物。这些复合物构成了循环 IGF 的稳定储备库，阻止了未结合的 IGF 潜在的低血糖活性。ALS 主要由肝细胞合成，在非肝脏组织中的表达较低。ALS 的合成受生长激素强烈诱导，受 IL-1β 抑制，因此可能作为生长激素分泌和/或活性以及炎症的标志物。人类的 IGFALS 突变和小鼠的 Igfals 缺失导致生长迟缓和青春期延迟，伴随着成骨减少和脂肪生成增强。在肝细胞癌中，IGFALS 被描述为肿瘤抑制因子；然而，它在其他癌症中的作用尚不清楚。这篇综述讨论了 ALS 的内分泌生理学和病理学，讨论了最新的细胞和蛋白质组学研究，这些研究表明 ALS 具有新兴的细胞作用，并概述了它在其他疾病状态中的参与。
