Inhibitory effects of trichostatin A on adrenocorticotropic hormone production and proliferation of corticotroph tumor AtT-20 cells

Yuki Nakada; Kazunori Kageyama; Aya Sugiyama; Rie Desaki; Shinobu Takayasu; Kanako Niioka; Shingo Murasawa; Noriko Ishigame; Yuko Asari; Yasumasa Iwasaki; Makoto Daimon

doi:10.1507/endocrj.EJ15-0369

ORIGINALS

Inhibitory effects of trichostatin A on adrenocorticotropic hormone production and proliferation of corticotroph tumor AtT-20 cells

Yuki Nakada, Kazunori Kageyama, Aya Sugiyama, Rie Desaki, Shinobu Takayasu, Kanako Niioka, Shingo Murasawa, Noriko Ishigame, Yuko Asari, Yasumasa Iwasaki, Makoto Daimon

Author information

Yuki Nakada
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Aomori 036-8562, Japan
Kazunori Kageyama
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Aomori 036-8562, Japan
Department of Endocrinology, Metabolism, and Infectious Diseases, Hirosaki University School of Medicine & Hospital, Aomori 036-8563, Japan
Aya Sugiyama
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Aomori 036-8562, Japan
Rie Desaki
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Aomori 036-8562, Japan
Shinobu Takayasu
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Aomori 036-8562, Japan
Department of Endocrinology, Metabolism, and Infectious Diseases, Hirosaki University School of Medicine & Hospital, Aomori 036-8563, Japan
Kanako Niioka
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Aomori 036-8562, Japan
Shingo Murasawa
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Aomori 036-8562, Japan
Noriko Ishigame
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Aomori 036-8562, Japan
Yuko Asari
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Aomori 036-8562, Japan
Yasumasa Iwasaki
Health Care Center, Kochi University, Kochi 780-8520, Japan
Makoto Daimon
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Aomori 036-8562, Japan

Keywords: Cushing’s disease, Adrenocorticotropic hormone (ACTH), Proopiomelanocortin (POMC), Pituitary tumor, Trichostatin

JOURNAL FREE ACCESS

2015 Volume 62 Issue 12 Pages 1083-1090

DOI https://doi.org/10.1507/endocrj.EJ15-0369

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Abstract

Cushing’s disease is primarily caused by adrenocorticotropic hormone (ACTH)-producing pituitary adenomas. Pituitary tumor-transforming gene 1 (PTTG1) expression, a hallmark of pituitary tumors, stimulates pituitary cell proliferation. Histone deacetylases (HDACs) play an important role in regulating gene transcription and HDAC inhibitors induce cellular differentiation and suppress tumor cell proliferation. HDAC inhibitors also repress PTTG1 mRNA levels. Trichostatin A (TSA) is a potent cell-permeable HDAC inhibitor that blocks cell cycle progression. In the present study, we determined the effect of TSA on ACTH production and cellular proliferation in mouse AtT-20 corticotroph tumor cells. TSA decreased proopiomelanocortin (POMC) mRNA levels in AtT-20 cells and reduced ACTH levels in the culture medium of these cells. The TSA-induced decreases in POMC mRNA levels were not modulated when TSA and dexamethasone were simultaneously administered. Drug treatment also decreased AtT-20 cell proliferation, induced apoptosis, and increased the percentage of cells in G0/G1 phase using flow cytometry. TSA decreased PTTG1 mRNA levels. Furthermore, PTTG1 knockdown inhibited cellular proliferation. Its knockdown also inhibited POMC mRNA and ACTH levels. TSA inhibits ACTH production and corticotroph tumor cell proliferation. TSA may inhibit cellular proliferation, and ACTH synthesis and secretion by decreasing PTTG1 expression.

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