Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Department of Experimental Immunotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Front Endocrinol (Lausanne). 2023 Mar 29;14:1124646. doi: 10.3389/fendo.2023.1124646. eCollection 2023.
Pituitary neuroendocrine corticotroph tumors commonly cause Cushing's disease (CD) that results from increased adrenocorticotropic hormone (ACTH) secretion by the pituitary tumor and consequent increase of cortisol levels in blood. However, in some patients, corticotroph tumors remain clinically non-functioning. Cortisol secretion is regulated by the hypothalamic-pituitary-adrenal axis and includes a negative feedback between cortisol and ACTH secretion. Glucocorticoids reduce ACTH level both by hypothalamic regulation and acting on corticotrophs glucocorticoid (GR) and mineralocorticoid (MR) receptors. The aim of the study was to determine the role of GR and MR expression at mRNA and protein levels in both functioning and silent corticotroph tumors.
Ninety-five patients were enrolled, including 70 with CD and 25 with silent corticotroph tumors. Gene expression levels of and coding for GR and MR, respectively, were determined with qRT-PCR in the two tumor types. GR and MR protein abundance was assessed with immunohistochemistry.
Both GR and MR were expressed in corticotroph tumors. Correlation between and expression levels was observed. expression was higher in silent than in functioning tumors. In CD patients and levels were negatively correlated with morning plasma ACTH levels and tumor size. Higher was confirmed in patients with remission after surgery and in densely granulated tumors. Expression of both genes and GR protein was higher in -mutated tumors. Similar relationship between mutations and expression levels were observed in analysis of silent tumors that also revealed a negative correlation between GR and tumor size and higher expression in densely granulated tumors.
Although the associations between gene/protein expression and patients clinical features are not strong, they consistently show an evident trend in which higher receptor expression corresponds to more favorable clinical characteristics.
垂体神经内分泌促皮质细胞瘤常导致库欣病（CD），这是由于垂体肿瘤促肾上腺皮质激素（ACTH）分泌增加，以及随之而来的血液中皮质醇水平升高所致。然而，在一些患者中，促皮质细胞瘤仍然没有临床表现。皮质醇的分泌受下丘脑-垂体-肾上腺轴的调节，包括皮质醇和 ACTH 分泌之间的负反馈。糖皮质激素通过下丘脑调节和作用于促皮质细胞上的糖皮质激素（GR）和盐皮质激素（MR）受体来降低 ACTH 水平。本研究的目的是确定 GR 和 MR 在功能性和无功能性促皮质细胞瘤中 mRNA 和蛋白水平表达的作用。
共纳入 95 例患者，其中 70 例为 CD，25 例为无功能性促皮质细胞瘤。分别用 qRT-PCR 检测两种肿瘤类型中编码 GR 和 MR 的基因表达水平。用免疫组织化学法评估 GR 和 MR 蛋白丰度。
GR 和 MR 均在促皮质细胞瘤中表达。观察到 与 表达水平之间存在相关性。无功能性肿瘤中 表达高于功能性肿瘤。在 CD 患者中，清晨血浆 ACTH 水平和肿瘤大小与 和 水平呈负相关。手术后缓解的患者和颗粒密集的肿瘤中 表达水平更高。在 突变的肿瘤中，两种基因和 GR 蛋白的表达均更高。在对无功能性肿瘤的分析中也观察到 突变与表达水平之间存在相似的关系，还揭示了 GR 与肿瘤大小呈负相关，以及颗粒密集的肿瘤中 表达水平更高。
尽管基因/蛋白表达与患者临床特征之间的关联并不强，但它们始终表现出一个明显的趋势，即受体表达水平越高，临床特征越好。
