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食欲素 A 增强 BMP-4 对小鼠 corticotrope AtT20 细胞中 pro-opiomelanocortin 转录的调节作用。

Orexin A Enhances Pro-Opiomelanocortin Transcription Regulated by BMP-4 in Mouse Corticotrope AtT20 Cells.

机构信息

Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan.

Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan.

出版信息

Int J Mol Sci. 2021 Apr 27;22(9):4553. doi: 10.3390/ijms22094553.

DOI:10.3390/ijms22094553
PMID:33925368
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8123825/
Abstract

Orexin is expressed mainly in the hypothalamus and is known to activate the hypothalamic-pituitary-adrenal (HPA) axis that is involved in various stress responses and its resilience. However, the effects of orexin on the endocrine function of pituitary corticotrope cells remain unclear. In this study, we investigated the roles of orexin A in pro-opiomelanocortin (POMC) transcription using mouse corticotrope AtT20 cells, focusing on the bone morphogenetic protein (BMP) system expressed in the pituitary. Regarding the receptors for orexin, type 2 (OXR2) rather than type 1 (OX1R) receptor mRNA was predominantly expressed in AtT20 cells. It was found that orexin A treatment enhanced POMC expression, induced by corticotropin-releasing hormone (CRH) stimulation through upregulation of CRH receptor type-1 (CRHR1). Orexin A had no direct effect on the POMC transcription suppressed by BMP-4 treatment, whereas it suppressed Smad1/5/9 phosphorylation and Id-1 mRNA expression induced by BMP-4. It was further revealed that orexin A had no significant effect on the expression levels of type I and II BMP receptors but upregulated inhibitory Smad6/7 mRNA and protein levels in AtT20 cells. The results demonstrated that orexin A upregulated CRHR signaling and downregulated BMP-Smad signaling, leading to an enhancement of POMC transcription by corticotrope cells.

摘要

食欲素主要在下丘脑表达，已知其可激活下丘脑-垂体-肾上腺（HPA）轴，该轴参与各种应激反应及其弹性。然而，食欲素对垂体促肾上腺皮质细胞内分泌功能的影响尚不清楚。在这项研究中，我们使用鼠促肾上腺皮质 AtT20 细胞研究了食欲素 A 在促阿黑皮素原（POMC）转录中的作用，重点研究了在垂体中表达的骨形态发生蛋白（BMP）系统。关于食欲素受体，AtT20 细胞中主要表达 2 型（OXR2）而非 1 型（OX1R）受体 mRNA。研究发现，食欲素 A 通过上调促肾上腺皮质激素释放激素受体 1（CRHR1）增强了由促肾上腺皮质激素释放激素（CRH）刺激诱导的 POMC 表达。食欲素 A 对 BMP-4 处理抑制的 POMC 转录没有直接作用，但抑制了 BMP-4 诱导的 Smad1/5/9 磷酸化和 Id-1 mRNA 表达。进一步表明，食欲素 A 对 I 型和 II 型 BMP 受体的表达水平没有显著影响，但在 AtT20 细胞中上调了抑制性 Smad6/7 mRNA 和蛋白水平。结果表明，食欲素 A 上调了 CRHR 信号，下调了 BMP-Smad 信号，从而增强了促肾上腺皮质细胞中 POMC 的转录。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e10a/8123825/864f7fa570b6/ijms-22-04553-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e10a/8123825/d23105d882c8/ijms-22-04553-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e10a/8123825/d0a3f7427aa5/ijms-22-04553-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e10a/8123825/62757d9a09d3/ijms-22-04553-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e10a/8123825/864f7fa570b6/ijms-22-04553-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e10a/8123825/d23105d882c8/ijms-22-04553-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e10a/8123825/d0a3f7427aa5/ijms-22-04553-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e10a/8123825/62757d9a09d3/ijms-22-04553-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e10a/8123825/864f7fa570b6/ijms-22-04553-g004.jpg

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