Exp Clin Endocrinol Diabetes 2020; 128(04): 263-269
DOI: 10.1055/a-0808-4227
Article
© Georg Thieme Verlag KG Stuttgart · New York

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

Jia Yang
1   Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
,
Yehong Yang
1   Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
,
Yongfei Wang
2   Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
,
Shuo Zhang
1   Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
,
Haixia Cheng
3   Department of Neuropathology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
,
Shuyang Wang
4   Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China
,
Liang Ge
5   Department of Interventional Radiology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
,
Yiming Li
1   Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
,
Hongying Ye
1   Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
› Author Affiliations
Acknowledgments This study was funded by Scientific Research project supported by Huashan Hospital, Fudan University(2016QD080).
Further Information

Publication History

received 10 October 2018
revised 16 November 2018

accepted 27 November 2018

Publication Date:
22 January 2019 (online)

Abstract

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.

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.

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.

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.

Supplementary Material

 
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