Differential effects of β-arrestin1 and β-arrestin2 on somatostatin receptors in murine AtT-20 corticotroph tumor cells

  • Kageyama Kazunori
    Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan
  • Hagiwara Rie
    Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan
  • Niioka Kanako
    Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan
  • Takayasu Shinobu
    Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan
  • Daimon Makoto
    Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan

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<p>Autonomous production of adrenocorticotropic hormone (ACTH) from pituitary corticotroph adenomas is the primary cause of Cushing’s disease. Somatostatin receptor, a G protein-coupled receptor (GPCR), types 2 (SSTR2) and 5 (SSTR5) mRNA expression is greater than that of other SSTR subtypes in human corticotroph adenomas. Further, the multiligand SOM230 shows potent effects in decreasing ACTH plasma levels and urinary free cortisol levels in patients with Cushing’s disease. We previously showed that both Sstr2 and Sstr5 mRNA levels were unaffected by SOM230 treatment, suggesting that both receptors might not be downregulated by the agonist. Intracellular molecules, such as β-arrestins, modulate ligand activated-receptor responses. In the present study, we determined regulation of β-arrestin1 and β-arrestin2 by SOM230 and dexamethasone in murine AtT-20 corticotroph tumor cells. In addition, we examined the effects of β-arrestin1 and β-arrestin2 on Sstr mRNA and their protein levels. SOM230 treatment increased β-arrestin1 mRNA levels and did not alter β-arrestin2 mRNA levels. SOM230 treatment could induce β-arrestin1 production in corticotroph tumor cells. Dexamethasone treatment decreased β-arrestin2 mRNA levels. β-arrestin2 knockdown increased proopiomelanocortin, and both Sstr2 and Sstr5 mRNA and their protein levels. The β-arrestin2 knockdown-increased proopiomelanocortin mRNA levels were canceled by SOM230 treatment.</p>

収録刊行物

  • Endocrine Journal

    Endocrine Journal 68 (2), 163-170, 2021

    一般社団法人 日本内分泌学会

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