通过增强剂激活PGR异形调节,调节子宫内膜细胞中的孕激素信号
Skylar G Montague Redecke1, Austin Bell-Hensley2, MyeongJin Yi1
1Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, 27709, United States.
F&S science
|August 23, 2025
概括
远端增强剂控制子宫内膜细胞中的孕激素受体 (PGR) 异型,影响基因表达. 这一发现为患有PGR失衡的疾病提供了新的治疗目标.
科学领域:
- 内分泌学和生殖生物学
- 基因组学和分子生物学
- 细胞和分子生理学
背景情况:
- 孕激素受体 (PGR) 异型,PGR-A和PGR-B,在子宫内膜功能中发挥关键作用.
- 了解PGR异型的调节对于理解子宫内膜中的孕激素信号是必不可少的.
研究的目的:
- 在人类子宫内膜细胞中研究增强剂介导的PGR异型 (PGR-A和PGR-B) 调节.
- 确定调节PGR异形平衡如何影响对孕激素敏感的转录组和对子宫内膜功能相关的细胞组.
主要方法:
- 基于CRISPR的功能性基因组查发现了调节PGR的远端增强剂.
- 针对CRISPR调节的PGR同位体平衡,然后进行大量RNA测序和切割和运行分析.
- 工程结合的子宫内膜细胞被用基酸 (MPA) 治疗.
主要成果:
- 鉴定出两种调节PGR异形平衡的远端PGR增强剂.
- 调节异形平衡改变了孕激素调节的转录组,影响了炎症和细胞周期基因表达.
- 观察到PGR-A和PGR-B的不同基因组结合模式,这表明异型特异性基因调节.
结论:
- 远端增强剂在调节PGR异形平衡和塑造子宫内膜转录组方面发挥着重要作用.
- 这种增强剂调节扩大了对PGR的理解,超出了促进者级别的控制范围.
- 这些发现可能会为涉及PGR异型失衡的疾病确定新的治疗点.
相关概念视频
GPCRs Regulate Adenylyl Cylase Activity
5.9K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.9K
Hormonal Regulation of the Menstrual Cycle
690
The ovarian cycle regulates endometrial changes throughout a single menstrual cycle via the coordinated action of gonadotrophin-releasing hormone (GnRH) and gonadotrophins.
At puberty, GnRH begins a pulsatile release pattern, which triggers the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The frequency and amplitude of GnRH pulses vary across the menstrual cycle, with faster pulses favoring LH release and slower pulses favoring FSH...
At puberty, GnRH begins a pulsatile release pattern, which triggers the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The frequency and amplitude of GnRH pulses vary across the menstrual cycle, with faster pulses favoring LH release and slower pulses favoring FSH...
690
GPCR Desensitization
6.5K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
6.5K
TGF - β Signaling Pathway
7.6K
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...
7.6K
Cell Specific Gene Expression
13.9K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.9K
Regulation of Expression at Multiple Steps
996
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
996


