Aghili Zahra Sadat, Khoshnevisan Golnoosh, Mostoli Rezvan, Alibaglouei Mehdi, Zarkesh-Esfahani Sayyed Hamid
Department of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.
Mol Biol Rep. 2025 Feb 4;52(1):202. doi: 10.1007/s11033-025-10304-w.
Growth hormone (GH) is a key polypeptide hormone secreted by somatotroph cells in the anterior pituitary gland, essential for postnatal growth, metabolism, and systemic homeostasis. Its secretion is regulated by hypothalamic neuropeptides, including GH-releasing hormone and somatostatin. GH exerts effects through direct interaction with the growth hormone receptor and indirect pathways mediated by the GH-IGF-I axis. GHR activation triggers signaling pathways, such as JAK-STAT, PI3K/AKT, and MAPK, promoting cellular proliferation, differentiation, and metabolic balance. The GH-IGF-I axis is critical for bone growth, lipid and carbohydrate metabolism, and organ-specific physiological functions. Dysregulation of GH results in diverse disorders. Congenital deficiencies, like isolated GH deficiency and syndromic conditions (e.g., Turner syndrome), stem from genetic mutations. Acquired deficiencies arise from trauma, tumors, infections, or autoimmune damage, while GH overproduction causes gigantism in children and acromegaly in adults, often due to pituitary adenomas. Idiopathic deficiencies, lacking identifiable causes, complicate management further. Advances in therapy have transformed outcomes for GH disorders. Recombinant human growth hormone provides effective replacement therapy for deficiencies. Somatostatin analogs, dopamine receptor agonists, and GH receptor antagonists are pivotal for managing GH excess. Surgical and radiotherapeutic interventions remain essential for pituitary adenomas. However, GH therapy requires close monitoring to prevent side effects like insulin resistance and metabolic complications. This review provides a comprehensive evaluation of the molecular mechanisms underlying GH action, its physiological roles, GH-related disorders, and therapeutic approaches to optimize patient outcomes.
生长激素（GH）是一种由垂体前叶促生长激素细胞分泌的关键多肽激素，对出生后的生长、代谢和全身稳态至关重要。其分泌受下丘脑神经肽调节，包括生长激素释放激素和生长抑素。GH通过与生长激素受体直接相互作用以及由GH-IGF-I轴介导的间接途径发挥作用。GHR激活触发信号通路，如JAK-STAT、PI3K/AKT和MAPK，促进细胞增殖、分化和代谢平衡。GH-IGF-I轴对骨骼生长、脂质和碳水化合物代谢以及器官特异性生理功能至关重要。GH失调会导致多种疾病。先天性缺陷，如孤立性生长激素缺乏症和综合征性疾病（如特纳综合征），源于基因突变。获得性缺陷由创伤、肿瘤、感染或自身免疫损伤引起，而GH分泌过多则导致儿童巨人症和成人肢端肥大症，通常是由于垂体腺瘤。特发性缺陷缺乏可识别的病因，进一步使管理复杂化。治疗进展改变了生长激素疾病的治疗结果。重组人生长激素为生长激素缺乏症提供了有效的替代疗法。生长抑素类似物、多巴胺受体激动剂和生长激素受体拮抗剂对于控制生长激素过多至关重要。手术和放射治疗干预对于垂体腺瘤仍然至关重要。然而，生长激素治疗需要密切监测，以预防胰岛素抵抗和代谢并发症等副作用。本综述全面评估了生长激素作用的分子机制、其生理作用、与生长激素相关的疾病以及优化患者治疗结果的治疗方法。
