Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
Front Endocrinol (Lausanne). 2023 Jun 15;14:1212104. doi: 10.3389/fendo.2023.1212104. eCollection 2023.
AXL is a receptor tyrosine kinase commonly associated with a variety of human cancers. Along with its ligand Gas6 (growth arrest-specific protein 6), AXL is emerging as an important regulator of neuroendocrine development and function. AXL signaling in response to Gas6 binding impacts neuroendocrine structure and function at the level of the brain, pituitary, and gonads. During development, AXL has been identified as an upstream inhibitor of gonadotropin receptor hormone (GnRH) production and also plays a key role in the migration of GnRH neurons from the olfactory placode to the forebrain. AXL is implicated in reproductive diseases including some forms of idiopathic hypogonadotropic hypogonadism and evidence suggests that AXL is required for normal spermatogenesis. Here, we highlight research describing AXL/Gas6 signaling mechanisms with a focus on the molecular pathways related to neuroendocrine function in health and disease. In doing so, we aim to present a concise account of known AXL/Gas6 signaling mechanisms to identify current knowledge gaps and inspire future research.
AXL 是一种受体酪氨酸激酶，通常与多种人类癌症有关。AXL 与其配体 Gas6（生长停滞特异性蛋白 6）一起，正在成为神经内分泌发育和功能的重要调节因子。AXL 信号对 Gas6 结合的反应会影响大脑、垂体和性腺水平的神经内分泌结构和功能。在发育过程中，AXL 被确定为促性腺激素受体激素 (GnRH) 产生的上游抑制剂，并且在 GnRH 神经元从嗅基板迁移到前脑的过程中也发挥关键作用。AXL 与包括某些形式的特发性促性腺激素低下性性腺功能减退症在内的生殖疾病有关，并且有证据表明 AXL 是正常精子发生所必需的。在这里，我们重点介绍描述 AXL/Gas6 信号机制的研究，重点介绍与健康和疾病中的神经内分泌功能相关的分子途径。这样做的目的是提供已知 AXL/Gas6 信号机制的简明说明，以确定当前的知识空白并激发未来的研究。
