Related Experiment Video
Updated: Sep 26, 2025
A Novel Method: Super-selective Adrenal Venous Sampling
Published on: September 15, 2017
Responsiveness to DDAVP in Cushing's disease is associated with USP8 mutations through enhancing AVPR1B promoter
Hiroki Shichi1, Hidenori Fukuoka2, Maki Kanzawa3
1Division of Diabetes and Endocrinology, Kobe University School of Medicine, Kobe, Japan.
Purpose:
To clarify the characteristics of Cushing's disease (CD) patients who respond to the desmopressin (DDAVP) test and its underlying mechanisms.
Methods:
Forty-seven patients with CD who underwent DDAVP testing were included. Patients were divided into two groups: DDAVP test (+) (adrenocorticotropic hormone [ACTH] levels increased by ≥ 1.5-fold during the DDAVP test) and DDAVP test (-) (ACTH levels increased by < 1.5-fold). AVP receptor expression levels in these tumors were quantified using quantitative RT-PCR and immunohistochemistry. AVP receptor promoter activity was analyzed using a dual-luciferase reporter assay system.
Results:
Females (96.9%) and USP8 mutants (85.7%) were more prevalent in the DDAVP test (+) than in the DDAVP test (-). Indeed, the ACTH and cortisol responsiveness to DDAVP was greater in USP8 mutation positive tumors than that in USP8 wild type tumors (3.0-fold vs. 1.3-fold, 1.6-fold vs. 1.1-fold, respectively). Responsiveness to DDAVP was correlated with the expression levels of AVPR1B, but not with those of AVPR2. Comparably, Avpr1b promoter activity was enhanced by the overexpression of mutant USP8 compared to the wild type.
Conclusions:
We found that the responsiveness of ACTH to DDAVP in CD was greater in tumors with USP8 mutations. The present data suggest that USP8 mutations upregulate the AVPR1B promoter activity. Additionally, we showed that the DDAVP test can predict the presence of USP8 mutations.
More Related Videos
08:46Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium
Published on: September 1, 2015
07:44Non-Invasive Ultrasound Assessment of Endometrial Cancer Progression in Pax8-Directed Deletion of the Tumor Suppressors Arid1a and Pten in Mice
Published on: February 17, 2023
Related Concept Videos
02:23Abnormal Proliferation
01:09GPCRs Regulate Adenylyl Cylase Activity
01:27Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
01:27Adrenal Gland Disorders
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...
01:28Global Regulatory Systems
01:26Adrenergic Receptors: β Subtype
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...