Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan.
Suzuka University of Medical Science, 1001-1 Kishioka-cho, Suzuka, Mie 510-0293, Japan.
Peptides. 2022 Sep;155:170841. doi: 10.1016/j.peptides.2022.170841. Epub 2022 Jul 19.
Growth differentiation factor-15 (GDF15) is a stress-responsive cytokine that plays important roles in regulation of inflammatory responses, cell growth, and cell differentiation. However, the nature of these roles remains unclear. Here, we aimed to examine the regulatory effects of dexamethasone on Gdf15 expression in murine AtT-20 corticotroph cells. Human Gdf15 promoter-driven luciferase reporter constructs were transfected into corticotroph cells to analyze their promoter activity. The effects of time and concentration of dexamethasone on Gdf15 and proopiomelanocortin (Pomc) mRNA levels were assessed using quantitative real-time polymerase chain reaction. Dexamethasone induced Gdf15 transcription and mRNA levels as well as GDF15 production in transfected cells, whereas reduced the Pomc mRNA levels. GDF15 modulated adrenocorticotropic hormone (ACTH) synthesis, and the dexamethasone-mediated reduction in Pomc mRNA levels were partially relieved upon Gdf15 knockdown. We concluded that GDF15 modulated ACTH production in pituitary corticotrophs in an autocrine manner by suppressing Pomc expression and subsequently mediating the negative feedback effect of glucocorticoids, thereby contributing to pituitary stress response and homeostasis.
生长分化因子 15（GDF15）是一种应激反应细胞因子，在调节炎症反应、细胞生长和细胞分化方面发挥着重要作用。然而，这些作用的性质尚不清楚。在这里，我们旨在研究地塞米松对鼠 AtT-20 嗜铬细胞瘤细胞中 Gdf15 表达的调节作用。将人 Gdf15 启动子驱动的荧光素酶报告基因构建体转染入嗜铬细胞瘤细胞，以分析其启动子活性。使用定量实时聚合酶链反应评估地塞米松对 Gdf15 和 proopiomelanocortin（Pomc）mRNA 水平的时间和浓度的影响。地塞米松诱导转染细胞中的 Gdf15 转录和 mRNA 水平以及 GDF15 产生，而降低 Pomc mRNA 水平。GDF15 调节促肾上腺皮质激素（ACTH）的合成，并且 Gdf15 敲低部分缓解了地塞米松介导的 Pomc mRNA 水平降低。我们得出结论，GDF15 通过抑制 Pomc 表达并随后介导糖皮质激素的负反馈作用，以自分泌方式调节垂体嗜铬细胞瘤中的 ACTH 产生，从而有助于垂体应激反应和体内平衡。
