Growth differentiation factor-15 modulates adrenocorticotropic hormone synthesis in murine AtT-20 corticotroph cells

被引：3

作者：

Kageyama, Kazunori ^{[1
]}

Iwasaki, Yasumasa ^{[2
]}

Watanuki, Yutaka ^{[1
]}

Murasawa, Shingo ^{[1
]}

Niioka, Kanako ^{[1
]}

Tasso, Mizuki ^{[1
]}

Kosugi, Ai ^{[1
]}

Daimon, Makoto ^{[1
]}

机构：

[1] Hirosaki Univ, Grad Sch Med, Dept Endocrinol & Metab, 5 Zaifu cho, Hirosaki, Aomori 0368562, Japan

[2] Suzuka Univ Med Sci, 1001-1 Kishioka Cho, Suzuka, Mie 5100293, Japan

来源：

PEPTIDES | 2022年 / 155卷

关键词：

Growth differentiation factor-15; Glucocorticoid; Corticotropin-releasing factor; Adrenocorticotropic hormone; Proopiomelanocortin; Pituitary; GLUCOCORTICOID-RECEPTOR; GENE; SUPERFAMILY; MECHANISMS; SECRETION; FEEDBACK; CACHEXIA; PEPTIDE; AXIS;

D O I：

10.1016/j.peptides.2022.170841

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Growth differentiation factor-15 (GDF15) is a stress-responsive cytokine that plays important roles in regulation of inflammatory responses, cell growth, and cell differentiation. However, the nature of these roles remains unclear. Here, we aimed to examine the regulatory effects of dexamethasone on Gdf15 expression in murine AtT20 corticotroph cells. Human Gdf15 promoter-driven luciferase reporter constructs were transfected into corticotroph cells to analyze their promoter activity. The effects of time and concentration of dexamethasone on Gdf15 and proopiomelanocortin (Pomc) mRNA levels were assessed using quantitative real-time polymerase chain reaction. Dexamethasone induced Gdf15 transcription and mRNA levels as well as GDF15 production in transfected cells, whereas reduced the Pomc mRNA levels. GDF15 modulated adrenocorticotropic hormone (ACTH) synthesis, and the dexamethasone-mediated reduction in Pomc mRNA levels were partially relieved upon Gdf15 knockdown. We concluded that GDF15 modulated ACTH production in pituitary corticotrophs in an autocrine manner by suppressing Pomc expression and subsequently mediating the negative feedback effect of glucocorticoids, thereby contributing to pituitary stress response and homeostasis.

引用

页数：7