Possible Good News! Effects of Tubastatin A on Adrenocorticotropic Hormone Synthesis and Proliferation of Att-20 Corticotroph Tumor Cells

[~MaryO~]

• Rie Hagiwara

  Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan

• Kazunori Kageyama

  Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan

• Yasumasa Iwasaki

  Suzuka University of Medical Science, Suzuka 510-0293, Japan

• Kanako Niioka

  Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan

• Makoto Daimon

  Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan

Keywords: Cushing’s disease, Adrenocorticotropic hormone, Proopiomelanocortin, Corticotroph tumor, Histone deacetylase

 

https://doi.org/10.1507/endocrj.EJ21-0778

 

Abstract

 

Cushing’s disease is an endocrine disorder characterized by hypercortisolism, mainly caused by autonomous production of ACTH from pituitary adenomas.

Autonomous ACTH secretion results in excess cortisol production from the adrenal glands, and corticotroph adenoma cells disrupt the normal cortisol feedback mechanism. Pan-histone deacetylase (HDAC) inhibitors inhibit cell proliferation and ACTH production in AtT-20 corticotroph tumor cells. A selective HDAC6 inhibitor has been known to exert antitumor effects and reduce adverse effects related to the inhibition of other HDACs.

The current study demonstrated that the potent and selective HDAC6 inhibitor tubastatin A has inhibitory effects on proopiomelanocortin (Pomc) and pituitary tumor-transforming gene 1 (Pttg1) mRNA expression, involved in cell proliferation. The phosphorylated Akt/Akt protein levels were increased after treatment with tubastatin A.

Therefore, the proliferation of corticotroph cells may be regulated through the Akt-Pttg1 pathway. Dexamethasone treatment also decreased the Pomc mRNA level. Combined tubastatin A and dexamethasone treatment showed additive effects on the Pomc mRNA level.

Thus, tubastatin A may have applications in the treatment of Cushing’s disease.

 

Access the PDF at https://www.jstage.jst.go.jp/article/endocrj/advpub/0/advpub_EJ21-0778/_pdf/-char/en