Kopchick J J, Parkinson C, Stevens E C, Trainer P J
Edison Biotechnology Institute, Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA.
Endocr Rev. 2002 Oct;23(5):623-46. doi: 10.1210/er.2001-0022.
An understanding of the events that occur during GH receptor (GHR) signaling has facilitated the development of a GHR antagonist (pegvisomant) for use in humans. This molecule has been designed to compete with native GH for the GHR and to prevent its proper or functional dimerization-a process that is critical for GH signal transduction and IGF-I synthesis and secretion. Clinical trials in patients with acromegaly show GHR blockade to be an exciting new mode of therapy for this condition, and pegvisomant may have a therapeutic role in diseases, such as diabetes and malignancy, in which abnormalities of the GH/IGF-I axis have been observed. This review charts the discovery and development of GHR antagonists and details the experience gained in patients with acromegaly.
对生长激素受体（GHR）信号传导过程中发生的事件的理解促进了用于人类的GHR拮抗剂（培维索孟）的开发。该分子被设计用于与天然生长激素竞争GHR，并阻止其正常或功能性二聚化——这一过程对于生长激素信号转导以及胰岛素样生长因子-I（IGF-I）的合成与分泌至关重要。对肢端肥大症患者的临床试验表明，GHR阻断是治疗这种疾病的一种令人兴奋的新疗法，培维索孟可能在诸如糖尿病和恶性肿瘤等观察到生长激素/IGF-I轴异常的疾病中发挥治疗作用。本综述阐述了GHR拮抗剂的发现与开发，并详细介绍了在肢端肥大症患者中获得的经验。
