孕激素和cAMP通过PGR和CREB1协同诱导SHP2的表达在子宫 stromal decidualization期间
Peiyi Zhou1, Liqun Ouyang1, Ting Jiang1
1Xiamen City Key Laboratory of Metabolism, School of Pharmaceutical Sciences, Xiamen University, China.
The FEBS journal
|October 3, 2023
概括
这项研究揭示了孕激素受体 (PGR) 和CREB1如何在决定化过程中调节SHP2表达,这是胚胎植入的关键过程. 了解这种机制可以提高对生殖健康和怀孕成功的了解.
科学领域:
- 生殖生物学 生殖生物学
- 分子内分泌学分子内分泌学
- 细胞信号传递 细胞信号传递
背景情况:
- 胚胎植入过程中,子宫内膜异位瘤的决定性是至关重要的,其中断可能导致怀孕失败.
- 由PTPN11编码的信号蛋白SHP2通过整合各种信号,在控制决定化方面发挥着动态作用.
- 在决定化过程中PTPN11的精确转录调节仍然不完全理解.
研究的目的:
- 阐明调节SHP2表达的转录机制,以响应十足信号.
- 确定在人类子宫内膜 stromal 细胞 decidualization 期间参与 PTPN11 基因调节的特定转录因子和促进子区域.
主要方法:
- 使用雌激素,孕激素和cAMP进行人体子宫内膜层细胞的体外分离.
- 路西法酶记者测试以确定PTPN11基因的响应性促进子区域.
- 生物信息分析,电泳运动转移测定 (EMSA) 和染色体免疫沉 (ChIP) 来确认转录因子结合.
- 基因淘汰实验用于评估已识别的转录因子的功能作用.
主要成果:
- 孕激素和cAMP,但不是雌激素,在体外决定化过程中诱导了SHP2表达.
- 确定PTPN11基因的一个核心促进子区域 (-229bp到 +1bp) 对孕激素和cAMP有反应.
- 孕激素受体 (PGR) 和cAMP-响应元素结合蛋白1 (CREB1) 被证实是直接结合PTPN11促进因子.
- 击败PGR和CREB1显著抑制了由medroxyprogesterone乙酸和cAMP诱导的SHP2表达.
结论:
- PGR和CREB1直接与PTPN11促进体结合,以调节SHP2的表达,以响应下落信号.
- 这项研究阐明了在决定化过程中SHP2的转录控制.
- 这些发现有助于更深入地了解底层的分子机制子宫内膜脱胎及其对成功怀孕的影响.
相关概念视频
Proliferative Phase
519
The proliferative phase typically occurs after menstruation and lasts between 6 to 13 days in a standard 28-day cycle. This phase involves the reconstruction of the endometrium, guided by estrogen produced by the developing ovarian follicle.
Notably, the stratum basale, the basal layer of the endometrium, including the basal parts of the uterine glands, remains unaffected by menstruation. Stem cells in this layer undergo mitosis, regenerating the stratum functionalis and thickening the...
Notably, the stratum basale, the basal layer of the endometrium, including the basal parts of the uterine glands, remains unaffected by menstruation. Stem cells in this layer undergo mitosis, regenerating the stratum functionalis and thickening the...
519
Ovarian Cycle
1.3K
The menstrual cycle includes a critical component known as the ovarian cycle, which undergoes two main phases each month—the follicular phase and the luteal phase. The follicular phase is variable and averaging around 14 days. Ovulation, triggered by a surge in luteinizing hormone (LH), marks the transition between the two phases. The second phase, the luteal phase, is relatively consistent, lasting approximately 14 days, and is marked by the activity of the corpus luteum. While a cycle...
1.3K
Gonadal and Placental Hormones
1.5K
The gonads, namely the testes in males and the ovaries in females, are pivotal in producing gonadal hormones that orchestrate the intricate processes of sexual development and reproduction.
In males, testosterone is the primary gonadal androgen. It plays a central role in the maturation of male reproductive organs — the penis and testes. Additionally, testosterone is instrumental in the development of secondary sexual characteristics — a deep voice as well as facial and pubic hair...
In males, testosterone is the primary gonadal androgen. It plays a central role in the maturation of male reproductive organs — the penis and testes. Additionally, testosterone is instrumental in the development of secondary sexual characteristics — a deep voice as well as facial and pubic hair...
1.5K
Secretory Phase
800
The secretory phase of the menstrual cycle, spanning from day 14 to 28 in a typical 28-day cycle, is a period of significant physiological changes in the female reproductive system. This phase commences immediately after ovulation and is characterized by the preparation of the endometrium for potential embryo implantation.
Following ovulation, the corpus luteum, a temporary endocrine structure, produces progesterone and estrogens. These hormones stimulate the growth and coiling of endometrial...
Following ovulation, the corpus luteum, a temporary endocrine structure, produces progesterone and estrogens. These hormones stimulate the growth and coiling of endometrial...
800
TGF - β Signaling Pathway
7.4K
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...
7.4K
Cell Specific Gene Expression
13.6K
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...
13.6K


