Role of Vasopressin Receptor 2 and 3 in ACTH-Secreting Tumors and their Potential Therapeutic Implications

  • Jia Yang
    Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
  • Yehong Yang
    Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
  • Yongfei Wang
    Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
  • Shuo Zhang
    Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
  • Haixia Cheng
    Department of Neuropathology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
  • Shuyang Wang
    Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China
  • Liang Ge
    Department of Interventional Radiology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
  • Yiming Li
    Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
  • Hongying Ye
    Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China

抄録

<jats:title>Abstract</jats:title><jats:p> Purpose We investigated the expression of vasopressin receptor 2 and 3 on corticotrophin tumor cells, their role in regulating ACTH secretion, and their potential therapeutic implications.</jats:p><jats:p> Methods We retrospectively assessed 52 hospitalized patients with pathologically confirmed ACTH-secreting tumors. The expression of vasopressin receptor 2 and 3 was explored via qualitative and quantitative immunohistochemistry analyses. The role of vasopressin receptors in regulating ACTH secretion was further studied in the AtT-20 cell line.</jats:p><jats:p> Results Among 50 cases of pituitary corticotrophin adenoma, 31 were vasopressin receptor 2 positive, 38 were vasopressin receptor 3 positive, and 24 were both vasopressin receptor 2 and 3 positive. Two patients with ectopic ACTH syndrome were vasopressin receptor 3 positive, and one was also vasopressin receptor 2 positive. In 12 patients who underwent bilateral inferior petrosal sinus sampling before surgery, the central ACTH increment ratio after desmopressin stimulation was correlated with vasopressin receptor 2 but not with vasopressin receptor 3 staining intensity. In an in vitro study, the expression of both vasopressin receptor 2 and 3 on AtT-20 cells was confirmed. The vasopressin receptor 2 antagonist Tolvaptan inhibited desmopressin-induced ACTH secretion in a dose-dependent manner.</jats:p><jats:p> Conclusions Both vasopressin receptor 2 and 3 are expressed in ACTH-secreting tumors. Vasopressin receptor 2 rather than vasopressin receptor 3 is the primary receptor that seems to mediate the ACTH response in corticotrophin tumors. A vasopressin receptor 2 antagonist can inhibit ACTH secretion induced by desmopressin in AtT-20 cells.</jats:p>

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