生长激素/胰岛素样生长因子-1轴调控男性生殖功能的研究进展

doi:10.12280/gjszjk.20260109

摘要/Abstract

摘要：

生长激素（growth hormone，GH）/胰岛素样生长因子-1（insulin-like growth factor-1，IGF-1）轴不仅参与机体生长发育和能量稳态维持，在男性生殖功能调控中也发挥重要作用。在中枢层面，IGF-1可通过影响下丘脑Kisspeptin/神经激肽B/强啡肽（Kisspeptin/neurokinin B/dynorphin，KNDy）神经元兴奋性，参与促性腺激素释放激素及黄体生成素分泌调控；在睾丸层面，GH/IGF-1轴可通过调节间质细胞和支持细胞功能、增强睾丸对促性腺激素的反应性、改善局部生精微环境，从而影响睾酮合成与精子发生；在外周效应层面，GH/IGF-1轴可能通过维持内皮细胞功能、调节一氧化氮/环磷酸鸟苷（nitric oxide/cyclic guanosine monophosphate，NO/cGMP）信号通路、支持神经修复及维持海绵体平滑肌稳态参与勃起功能调控。然而，现有证据仍以动物实验、体外研究及小样本临床观察为主，且GH/IGF-1轴对男性生殖功能的影响并非单向促进，尚缺乏高质量临床干预研究支持其常规应用。

关键词: 生长激素, 胰岛素样生长因子Ⅰ, 不育，男（雄）性, 垂体激素类, 勃起功能障碍

Abstract:

Growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis not only participates in body growth and development as well as energy homeostasis maintenance, but also plays a significant role in the regulation of male reproductive function. At the central level, IGF-1 can participate in the regulation of gonadotropin-releasing hormone and luteinizing hormone secretion through influencing the excitability of hypothalamic Kisspeptin/neurokinin B/dynorphin (KNDy) neurons. At the testicular level, the GH/IGF-1 axis can affect testosterone synthesis and spermatogenesis by regulating the functions of Leydig cells and Sertoli cells, enhancing the responsiveness of testis to gonadotropin, and improving the local microenvironment of spermatogenesis. At the peripheral effect level, GH/IGF-1 axis may participate in the regulation of erectile function by maintaining endothelial cell function, regulating the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signal pathway, supporting nerve repair and maintaining the stability of the smooth muscle of the corpus cavernosum. However, the existing evidence is mainly based on animal experiments, in vitro studies and small-sample clinical observations, and the impact of the GH/IGF-1 axis on male reproductive functions is not a one-way promotion. There is still a lack of high-quality clinical intervention studies to support its routine application.

Key words: Growth hormone, Insulin-like growth factor Ⅰ, Infertility, male, Pituitary hormones, Erectile dysfunction

陈天泽, 王丹丹, 洪菊生, 杨光平. 生长激素/胰岛素样生长因子-1轴调控男性生殖功能的研究进展[J]. 国际生殖健康/计划生育杂志, 2026, 45(4): 301-305.

CHEN Tian-ze, WANG Dan-dan, HONG Ju-sheng, YANG Guang-ping. Research Progress on the Growth Hormone/Insulin-Like Growth Factor-1 Axis in Regulating Male Reproductive Function[J]. Journal of International Reproductive Health/Family Planning, 2026, 45(4): 301-305.

参考文献 20

[1]	Bioletto F, Varaldo E, Gasco V, et al. Central and peripheral regulation of the GH/IGF-1 axis: GHRH and beyond[J]. Rev Endocr Metab Disord, 2025, 26(3):321-342. doi: 10.1007/s11154-024-09933-6.
[2]	Yuen K, Hjortebjerg R, Ganeshalingam AA, et al. Growth hormone/insulin-like growth factor I axis in health and disease states: an update on the role of intra-portal insulin[J]. Front Endocrinol(Lausanne), 2024, 15:1456195. doi: 10.3389/fendo. 2024.1456195.
[3]	Cannarella R, Crafa A, Sapienza S, et al. Testicular function in postpubertal patients with growth hormone deficiency: A prospective controlled study[J]. J Clin Transl Endocrinol, 2025, 39:100383. doi: 10.1016/j.jcte.2025.100383.
[4]	Liu G, Liu D, Zhu M, et al. Insulin-like growth factor-1 promotes the testicular sperm production by improving germ cell survival and proliferation in high-fat diet-treated male mice[J]. Andrology, 2025, 13(2):342-358. doi: 10.1111/andr.13645.
[5]	Otunctemur A, Ozbek E, Sahin S, et al. Low serum insulin-like growth factor-1 in patients with erectile dysfunction[J]. Basic Clin Androl, 2016, 26:1. doi: 10.1186/s12610-015-0028-x. pmid: 26823979
[6]	Silva J, de Sousa L, de Sousa ME, et al. KNDy neurons as an indirect target of insulin-like growth factor-1[J]. J Neuroendocrinol, 2026, 38(1):e70130. doi: 10.1111/jne.70130.
[7]	Wu Y, Li Q, Qi X, et al. Molecular characteristics and regulatory role of insulin-like growth factor 1 gene in testicular Leydig cells of Tibetan sheep[J]. Sci Rep, 2024, 14(1):24799. doi: 10.1038/s41598-024-75234-2. pmid: 39433555
[8]	Zhang Y, Qiu P, Lu J, et al. Identification of miR-34c-5p as a potential regulatory molecule associated with testicular development of black goat[J]. FASEB J, 2025, 39(5):e70384. doi: 10.1096/fj.202402519R.
[9]	Kumar K, Dutta M, Deori S, et al. Association between levels of insulin-like growth factor-1 in serum and seminal plasma with fresh and frozen-thawed semen characteristics in Beetal bucks[J]. Reprod Domest Anim, 2024, 59(1):e14499. doi: 10.1111/rda. 14499.
[10]	Ranjan R, Sharma K, Kumar M, et al. IGF-1 stabilizes goat sperm mitochondrial transmembrane potential and reduces dna fragmentation[J]. Cryo Letters, 2023, 44(6):327-332. doi:10.54680/fr23610110312. pmid: 38311926
[11]	Singh WL, Sinha S, Ahmed K, et al. IGF-1 outperforms vitamin E and crocin in improving semen quality, antioxidant profile and fertility gene expression in cryopreserved goat (Capra hircus) semen[J]. Anim Reprod Sci, 2025, 274:107791. doi: 10.1016/j.anireprosci.2025.107791.
[12]	Li Y, Wang J, Zhou T, et al. IGF1R as a protective target in antidiabetic drug-mediated prevention of erectile dysfunction: Insights from genetics[J]. Reprod Toxicol, 2025, 137:108999. doi: 10.1016/j.reprotox.2025.108999.
[13]	Pallotti F, Costa D, Hirsch MN, et al. Erectile function and androgen and estrogen beta receptor gene polymorphisms in acromegalic men[J]. J Endocrinol Invest, 2024, 47(1):141-147. doi: 10.1007/s40618-023-02131-2.
[14]	Chen Z, Shao X, He M, et al. Erectile Dysfunction Is Associated With Excessive Growth Hormone Levels in Male Patients With Acromegaly[J]. Front Endocrinol(Lausanne), 2021, 12:633904. doi: 10.3389/fendo.2021.633904.
[15]	Xu ZP, Wang HP, Liu JM, et al. Effects of insulin-like growth factor-1 on the relaxation responses of the cavernous smooth muscle from aged rats[J]. Scand J Urol, 2015, 49(3):260-266. doi: 10.3109/21681805.2015.1021832.
[16]	Ock J, Yin GN, Liu FY, et al. Ablation of IGFBP5 expression alleviates neurogenic erectile dysfunction by inducing neurovascular regeneration[J]. Investig Clin Urol, 2025, 66(1):74-86. doi: 10.4111/icu.20240325. pmid: 39791587
[17]	Tan X, Zhao L, Tang Y. The Function of BDNF and Its Receptor in the Male Genitourinary System and Its Potential Clinical Application[J]. Curr Issues Mol Biol, 2022, 45(1):110-121. doi: 10.3390/cimb45010008. pmid: 36661494
[18]	Sanchez-Bezanilla S, Beard DJ, Hood RJ, et al. Growth Hormone Increases BDNF and mTOR Expression in Specific Brain Regions after Photothrombotic Stroke in Mice[J]. Neural Plast, 2022, 2022:9983042. doi: 10.1155/2022/9983042.
[19]	Wang W, Liu Y, Zhou ZH, et al. Effects of human umbilical cord-derived mesenchymal stem cell therapy for cavernous nerve injury-induced erectile dysfunction in the rat model[J]. Asian J Androl, 2025, 27(4):508-515. doi: 10.4103/aja2024115.
[20]	Yang M, Chen X, Zhang M, et al. hUC-MSC preserves erectile function by restoring mitochondrial mass of penile smooth muscle cells in a rat model of cavernous nerve injury via SIRT1/PGC-1a/TFAM signaling[J]. Biol Res, 2025, 58(1):8. doi: 10.1186/s40659- 024-00578-y. pmid: 39871297