Cell Biology Department, Wuxi School of Medicine, Jiangnan University, 214122 Wuxi, Jiangsu, China; Department of Pathogen Biology, Guizhou Nursing Vocational College, Guiyang 550000, Guizhou, China.
Cell Biology Department, Wuxi School of Medicine, Jiangnan University, 214122 Wuxi, Jiangsu, China.
Int J Biol Macromol. 2024 Aug;275(Pt 1):133659. doi: 10.1016/j.ijbiomac.2024.133659. Epub 2024 Jul 3.
The age-related alterations in pituitary function, including changes in prolactin (PRL) production contributes to the systemic susceptibility to age-related diseases. Our previous research has shown the involvement of Nrg1 in regulating the expression and secretion of PRL. However, the precise role of Nrg1 in mitigating the senescence of pituitary lactotrophs and the underlying mechanisms are yet to be comprehended. Here, data from the GEPIA database was used to evaluate the association between transient receptor potential cation channel subfamily M member 8 (TRPM8) and PRL in normal human pituitary tissues, followed by immunofluorescence verification using a human pituitary tissue microarray. TRPM8 levels showed a significant positive association with PRL expression in normal human pituitary tissues, and both TRPM8 and PRL levels declined during aging, suggesting that TRPM8 may regulate pituitary aging by affecting PRL production. It was also found that treatment with exogenous neuregulin 1 (Nrg1) markedly delayed the senescence of GH3 cells (rat lactotroph cell line) generated by D-galactose (D-gal). In addition, melatonin reduced the levels of senescence-related markers in senescent pituitary cells by promoting Nrg1 / ErbB4 signaling, stimulating PRL expression and secretion. Further investigation showed that Nrg1 attenuated senescence in pituitary cells by increasing TRPM8 expression. Downregulation of TRPM8 activation eliminated Nrg1-mediated amelioration of pituitary cell senescence. These findings demonstrate the critical function of Nrg1 / ErbB signaling in delaying pituitary lactotroph cell senescence and enhancing PRL production via promoting TRPM8 expression under the modulation of melatonin.
垂体功能的年龄相关性改变，包括催乳素 (PRL) 产生的变化，导致了与年龄相关疾病的全身易感性。我们之前的研究表明，NRG1 参与调节 PRL 的表达和分泌。然而，NRG1 缓解垂体泌乳素细胞衰老的精确作用及其潜在机制尚不清楚。在这里，使用 GEPIA 数据库的数据评估瞬时受体电位阳离子通道亚家族 M 成员 8 (TRPM8)与正常人类垂体组织中 PRL 之间的关联，然后使用人类垂体组织微阵列进行免疫荧光验证。TRPM8 水平与正常人类垂体组织中 PRL 的表达呈显著正相关，并且 TRPM8 和 PRL 水平在衰老过程中均下降，这表明 TRPM8 可能通过影响 PRL 产生来调节垂体衰老。还发现，用外源性神经调节蛋白 1 (NRG1) 处理可显著延缓 D-半乳糖 (D-gal) 产生的 GH3 细胞 (大鼠泌乳素细胞系) 的衰老。此外，褪黑素通过促进 NRG1/ErbB4 信号转导、刺激 PRL 表达和分泌，降低衰老垂体细胞中的衰老相关标志物水平。进一步研究表明，NRG1 通过增加 TRPM8 表达来减轻垂体细胞衰老。TRPM8 激活的下调消除了 Nrg1 介导的对垂体细胞衰老的改善。这些发现表明，NRG1/ErbB 信号在通过促进 TRPM8 表达来延迟垂体泌乳素细胞衰老和增强 PRL 产生方面具有重要作用，这是在褪黑素的调节下实现的。
