孕妇X受体通过诱导性激素结合型球蛋白表达来调节人类内分泌系统
Maria H Ahonen1, Anja Konzack1, Tomas Smutny2
1Research Unit of Biomedicine and Internal Medicine, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
Basic & clinical pharmacology & toxicology
|March 6, 2026
概括
孕妇X受体 (PXR) 调节人类的性激素结合型全球蛋白 (SHBG) 水平. 激活PXR会增加SHBG,影响性激素平衡和代谢健康.
科学领域:
- 内分泌学 在内分泌学.
- 药理学 药理学是指药理学的学科.
- 肝病学 肝病学是一种肝病学.
背景情况:
- 性激素结合球蛋白 (SHBG) 是性激素的关键载体蛋白.
- 孕妇X受体 (PXR) 是药物代谢和异生物反应的关键调节器.
- 对于PXR在SHBG调节中的作用尚不清楚.
研究的目的:
- 研究PXR在人类SHBG调节中的作用.
- 描述PXR介导的SHBG调节背后的分子机制.
主要方法:
- 临床试验涉及健康的志愿者接受PXR连接体 (里芬素) 治疗.
- 在体外实验中使用人类3D肝细胞球体和HepG2细胞.
- 分析之前发表的染色体免疫沉降测序 (ChIP-seq) 数据.
主要成果:
- 在健康志愿者中,利芬素的使用显著增加了血清SHBG水平.
- 在人类肝细胞球体中,PXR激活诱导了SHBG mRNA表达.
- PXR对抗剂SPA70降低了SHBG mRNA的表达.
- ChIP-seq分析揭示了SHBG基因中的PXR结合部位.
结论:
- PXR是人类血清SHBG的一个新型调节剂.
- 通过PXR调节SHBG可能会影响性激素平衡.
- 这一发现对了解PXR激活药物对代谢健康的影响有意义.
相关概念视频
Transducer Mechanism: Nuclear Receptors
4.2K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
4.2K
Target Cell Response to Hormones
6.0K
Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
6.0K
Hormonal Regulation of the Menstrual Cycle
2.0K
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...
2.0K
Endocrine Signaling
68.7K
Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
68.7K
Gonadal and Placental Hormones
3.6K
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...
3.6K
Regulation of Hormone Secretion
7.2K
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...
7.2K


