库欣病（CD）是由皮质腺瘤的自主性促肾上腺皮质激素（ACTH）分泌引起的，导致过度皮质醇产生，最终影响发病率和死亡率。帕西雷酮是唯一获得FDA批准用于治疗CD的肿瘤定向治疗药物，但其对大约25%的患者有效，同时与高血糖的高发率相关。神经介质B（NMB）是bombesin样肽家族的成员之一，调节内分泌分泌和细胞增殖。在本研究中，我们评估了人垂体皮质腺瘤中NMB和NMB受体（NMBR）的表达以及NMBR拮抗剂PD168368对小鼠和人垂体腺瘤的作用。为了调查NMB和NMBR的表达，我们在人垂体瘤、非功能性瘤和生长激素瘤的病理标本上进行了实时荧光定量PCR和免疫染色。我们研究了PD168368在体外、体内和七种来源于患者的垂体腺瘤细胞中对激素分泌和细胞增殖的影响。相比于非功能性或生长激素瘤，人垂体腺瘤中表达NMB和NMBR的程度更高。在小鼠AtT-20细胞中，PD168368降低了前促黑激素（POMC）mRNA/蛋白表达和ACTH的分泌，以及细胞增殖。在移植瘤小鼠中，PD168368抑制了肿瘤生长、ACTH和皮质酮的表达。在来源于患者的腺瘤细胞中，PD168368降低了四例中的POMC mRNA表达和五例中的ACTH分泌。我们还在AtT-20和来源于患者的细胞中发现了PD168368介导的E型细胞周期蛋白抑制。NMBR拮抗剂可能是CD的潜在治疗方法，其作用可能通过抑制细胞周期蛋白E来发挥。© 2023. 作者，独家许可给Springer Science+Business Media, LLC, Springer Nature的一部分。

Cushing's disease (CD) results from autonomous adrenocorticotropic hormone (ACTH) secretion by corticotroph adenomas, leading to excessive cortisol production, ultimately affecting morbidity and mortality. Pasireotide is the only FDA approved tumor directed treatment for CD, but it is effective in only about 25% of patients, and is associated with a high rate of hyperglycemia. Neuromedin B (NMB), a member of the bombesin-like peptide family, regulates endocrine secretion and cell proliferation. Here, we assessed NMB and NMB receptor (NMBR) expression in human corticotroph adenomas and the effects of NMBR antagonist PD168368 on murine and human corticotroph tumors.To investigate NMB and NMBR expression, real-time qPCR and immunostaining on human pathological specimens of corticotroph, non-functional and somatotroph adenomas were performed. The effects of PD168368 on hormone secretion and cell proliferation were studied in vitro, in vivo and in seven patient-derived corticotroph adenoma cells. NMB and NMBR were expressed in higher extent in human corticotroph adenomas compared with non-functional or somatotroph adenomas.In murine AtT-20 cells, PD168368 reduced proopiomelanocortin (Pomc) mRNA/protein expression and ACTH secretion as well as cell proliferation. In mice with tumor xenografts, tumor growth, ACTH and corticosterone were downregulated by PD168368. In patient-derived adenoma cells, PD168368 reduced POMC mRNA expression in four out of seven cases and ACTH secretion in two out of five cases. A PD168368-mediated cyclin E suppression was also identified in AtT-20 and patient-derived cells.NMBR antagonist represents a potential treatment for CD and its effect may be mediated by cyclin E suppression.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.