增长激素通过GATA调节二氧化酶2型和3型的表达
Mana Mitsutani1, Hiromi Hano1, Mei Yokoyama1
1Medicine & Clinical Science, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo 663-8179, Japan.
概括
增长激素 (GH) 通过JAK/STAT5/GATA信号传递来调节甲状腺激素 (TH) 代氧酶 (DIO) 的表达. 这揭示了TH作用的GH依赖补偿的分子机制,这对生长和新陈代谢至关重要.
科学领域:
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
- 细胞生长调节 细胞生长调节
背景情况:
- 增长激素 (GH) 和甲状腺激素 (TH) 对生长至关重要,在荷尔蒙缺乏症中具有潜在的互补作用.
- 在GH和TH之间的相互作用的基础上的分子机制,特别是GH对TH代谢酶 (二氧化酶) 的作用,仍然在很大程度上是未知的.
- 了解这种相互作用是关键的,正如GH在Refetoff综合征中的无效性所示,这是由于TH受体功能障碍造成的.
研究的目的:
- 阐明GH影响2型 (DIO2) 和3型 (DIO3) 氨酸二氧化酶表达的分子机制.
- 研究参与GH调节DIO2和DIO3表达的信号通路.
- 探索 GATA 转录因子在调解 GH 对二氧激酶表达的影响中的作用.
主要方法:
- 记者测定和染色质免疫沉以分析促进体活性和转录因子结合.
- 定量PCR和西部涂抹以评估DIOs的mRNA和蛋白质表达水平.
- 在HEK293衍生TSA201细胞和小鼠ATDC5冠状细胞中进行的实验.
主要成果:
- 在ATDC5细胞中,GH显著诱导了DIO2和DIO3的mRNA和蛋白质表达.
- GH通过JAK/STAT5/GATA信号通路调解了这种诱导.
- 鉴定出GATA转录因子是DIO促进体活性的关键激活剂,鉴定出DIO2和DIO3.3的特定结合位点.
结论:
- 在与GH受体 (GHR) 结合后,GH通过JAK/STAT5/GATA通路直接调节DIO2和DIO3的表达.
- 这项研究提供了第一个关于GH如何补偿甲状腺激素作用的分子见解.
- 这些发现突出了GH和TH信号通路之间的交叉交谈的新机制,对生长和代谢调节有影响.
相关概念视频
TGF - β Signaling Pathway
10.5K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.5K
Synthesis and Regulation of Thyroid Hormones
7.2K
Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
7.2K
Functions of Thyroid Hormones
5.0K
The thyroid hormone (TH) plays a pivotal role in the intricate orchestration of physiological processes, exerting profound effects on development, metabolism, and homeostasis throughout different life stages.
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
5.0K
Activation and Inactivation of G Proteins
11.1K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
11.1K
Regulation of Hormone Secretion
6.2K
Regulation of hormone secretion is a finely tuned orchestration driven by various types of stimuli, encompassing neural, humoral, and hormonal signals. Environmental cues instigate neural stimuli, where action potentials traverse nerve fibers to reach their designated targets. An illustrative scenario is the body's response to stress, wherein the sympathetic nervous system releases epinephrine from the adrenal glands, inducing the well-known 'fight or flight' reaction.
Humoral...
Humoral...
6.2K
Master Transcription Regulators
7.7K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.7K


