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김지인 (연세대학교) 오주헌 (연세대학교 의과대학) Heather Harlem (Endocrinology Research Ipsen Bioscience Inc. Cambridge) Michael D. Culler (Endocrinology Research Ipsen Bioscience Inc. Cambridge) 구철룡 (연세대학교) 이은직 (연세대학교)
저널정보
대한내분비학회 Endocrinology and Metabolism Endocrinology and Metabolism Vol.35 No.1
발행연도
2020.1
수록면
177 - 187 (11page)

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Background: Acromegaly is a rare disease primarily caused by growth hormone (GH)-secreting pituitary adenomas, and its treatment is costly. Moreover, some patients are unresponsive to treatment. Hence, there are increasing efforts to develop new drugs withimproved effectiveness for this disease. BIM23B065 is a novel chimeric molecule that acts on both somatostatin and dopamine receptors. This study aimed to investigate the effects of BIM23B065 compared with those of a somatostatin receptor analog and a dopamine agonist. Methods: The effects of BIM23B065 on the proliferation, GH and insulin-like growth factor-1 (IGF-1) levels, and extracellular signal-regulated kinase (ERK) 1/2 and cyclic AMP response element binding (CREB) phosphorylation of GH3 cells were investigatedwith MTS assay, enzyme-linked immunosorbent assay, and Western blotting, respectively. The dosage and treatment duration ofBIM23B065 were tested in animal models of GH-secreting pituitary adenoma. The effect of BIM23B065 (3 mg/kg/day) on changesin IGF-1 levels before and after treatment was further investigated. Results: In vitro, BIM23B065 treatment decreased GH release in the culture media and downregulated ERK 1/2 and CREB phosphorylation to 22% and 26%, respectively. In vivo, IGF-1 expression decreased to 50 % after 4 weeks of treatment with BIM23B065using an osmotic pump implant. Moreover, magnetic resonance imaging results showed that the tumor size decreased significantlyfollowing treatment with BIM23B065 for 4 weeks. Conclusion: The novel chimeric molecule was effective in decreasing IGF-1 and GH levels and may serve as an effective therapeuticagent for acromegaly.

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