Characterization of SNARE Proteins in Human Pituitary Adenomas: Targeted Secretion Inhibitors as a New Strategy for the Treatment of Acromegaly?
2013
Context: Targeted secretion inhibitors (TSIs), a new class of recombinant biotherapeutic proteins engineered from botulinum toxin, represent a novel approach for treating diseases with excess secretion. They inhibit hormone secretion from targeted cell types through cleavage of SNARE (soluble N-ethylmaleimide-sensitive factor-activating protein receptor) proteins. qGHRH-LHN/D is a TSI targeting pituitary somatotroph through binding to the GHRH-receptor and cleavage of the vesicle-associated membrane protein (VAMP) family of SNARE proteins. Objective: Our objective was to study SNARE protein expression in pituitary adenomas and to inhibit GH secretion from somatotropinomas using qGHRH-LHN/D. Design: We analyzed human pituitary adenoma analysis for SNARE expression and response to qGHRH-LHN/D treatment. Setting: The study was conducted in University Hospitals. Patients: We used pituitary adenoma samples from 25 acromegaly and 47 nonfunctioning pituitary adenoma patients. Outcome: Vesicle-SNARE (VAMP1–3), ta...
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