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

Jia Yang; Yehong Yang; Yongfei Wang; Shuo Zhang; Haixia Cheng; Shuyang Wang; Liang Ge; Yiming Li; Hongying Ye

doi:10.1055/a-0808-4227

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2020; 128(04): 263-269
DOI: 10.1055/a-0808-4227

Article

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

Jia Yang

¹Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China

,

Yehong Yang

¹Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China

,

Yongfei Wang

²Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China

,

Shuo Zhang

¹Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China

,

Haixia Cheng

³Department of Neuropathology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China

,

Shuyang Wang

⁴Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China

,

Liang Ge

⁵Department of Interventional Radiology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China

,

Yiming Li

¹Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China

,

Hongying Ye

¹Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China

› Author Affiliations

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.

Key words

pituitary - Cushing's disease - ectopic ACTH syndrome - vasopressin receptor 2 antagonist

Full Text

References

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Supplementary Material

Supplementary Material