Peverelli Erika, Treppiedi Donatella, Mantovani Giovanna
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Endocrinology Unit, Milan, Italy.
Endocr Oncol. 2022 Mar 23;2(1):R24-R30. doi: 10.1530/EO-22-0042. eCollection 2022 Jan.
Adrenocorticotropic hormone (ACTH)-secreting pituitary tumors mainly express somatostatin receptor 5 (SSTR5) since SSTR2 is downregulated by the elevated levels of glucocorticoids that characterize patients with Cushing's disease (CD). SSTR5 is the molecular target of pasireotide, the only approved pituitary tumor-targeted drug for the treatment of CD. However, the molecular mechanisms that regulate SSTR5 are still poorly investigated. This review summarizes the experimental evidence supporting the role of the cytoskeleton actin-binding protein filamin A (FLNA) in the regulation of SSTR5 expression and signal transduction in corticotroph tumors. Moreover, the correlations between the presence of somatic USP8 mutations and the expression of SSTR5 will be reviewed. An involvement of glucocorticoid-mediated β-arrestins modulation in regulating SSTRs expression and function in ACTH-secreting tumors will also be discussed.
分泌促肾上腺皮质激素（ACTH）的垂体瘤主要表达生长抑素受体5（SSTR5），因为在库欣病（CD）患者中，糖皮质激素水平升高会下调SSTR2。SSTR5是帕瑞肽的分子靶点，帕瑞肽是唯一获批用于治疗CD的垂体瘤靶向药物。然而，调节SSTR5的分子机制仍未得到充分研究。本综述总结了支持细胞骨架肌动蛋白结合蛋白细丝蛋白A（FLNA）在促肾上腺皮质激素瘤中调节SSTR5表达和信号转导作用的实验证据。此外，还将综述体细胞USP8突变的存在与SSTR5表达之间的相关性。还将讨论糖皮质激素介导的β-抑制蛋白调节在促肾上腺皮质激素分泌肿瘤中调节SSTRs表达和功能方面的作用。
