FDXR变种会导致上腺功能不充分和异常性发育
Emanuele Pignatti1,2, Jesse Slone3, María Ángeles Gómez Cano4,5
1Division of Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, and.
JCI insight
|June 17, 2024
概括
铁素还原酶 (FDXR) 的遗传缺陷可以导致危及生命的上腺功能不全,特别是在压力期间. 这项研究揭示了FDXR变异会损害类固醇生产,导致皮质醇缺乏和与FDXR相关的线粒体病变患者的潜在死亡.
科学领域:
- 生物化学 生物化学
- 遗传学 是一个遗传学.
- 内分泌学 在内分泌学.
背景情况:
- 类固醇生物合成中的遗传缺陷导致皮质醇缺乏和性别发育的差异.
- 铁素减少酶 (FDXR) 的突变会导致与FDXR相关的线粒体病变 (FRM),但以前没有记录过皮质醇缺乏症.
- 患有FRM的患者可以在压力期间经历严重的疾病或死亡,例如感染.
研究的目的:
- 调查FDXR变异在上腺功能不全中的作用.
- 确定FDXR突变是否有助于FRM患者的皮质醇缺乏.
- 探索FDXR变种影响类固醇生成的机制.
主要方法:
- 对两名患有FRM和新型FDXR突变的女性患者的基因分析 (p.G437R).
- 从FRM纤维细胞中获得的细胞系的类固醇分析.
- 对Fdxr突变小鼠的表型分析.
主要成果:
- 研究的患者呈现出模两可的生殖器,皮质醇缺乏和雄激素过量,表明11-基酶缺乏.
- 在FDXR变异细胞系中,矿物质皮质和葡萄皮质的生产不足.
- Fdxr突变小鼠表现出降低的孕激素和皮质激素合成.
结论:
- 人类的FDXR变种可以在压力下引起补偿的,但可能危及生命的,上腺皮质缺陷.
- 这些变异可能会通过直接的酶抑制和被破坏的线粒体氧化还原平衡损害上腺葡萄糖皮质激素和矿物质皮质激素合成.
- 在对上腺功能不充分的差异诊断中,应考虑FDXR突变,特别是在FRM患者或在压力条件下.
相关概念视频
01:27Adrenal Gland Disorders
1.5K
Adrenal gland disorders manifest when the production of adrenal hormones deviates from the norm, resulting in either excessive or insufficient concentrations.
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...
1.5K
01:31Hormones of the Adrenal Glands
2.4K
Adrenal hormones play a pivotal role in maintaining the body's electrolyte balance and orchestrating responses to stress, showcasing the intricate functions of the adrenal cortex and medulla.
The adrenal cortex, a powerhouse of hormone synthesis, generates over two dozen corticosteroid hormones. The zona glomerulosa produces mineralocorticoids, exemplified by aldosterone, influencing the electrolyte composition of body fluids. The synthesis of glucocorticoids such as cortisol and...
The adrenal cortex, a powerhouse of hormone synthesis, generates over two dozen corticosteroid hormones. The zona glomerulosa produces mineralocorticoids, exemplified by aldosterone, influencing the electrolyte composition of body fluids. The synthesis of glucocorticoids such as cortisol and...
2.4K
01:43Sex-linked Disorders
102.0K
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
102.0K
01:11Renal Failure: Dose Adjustments
80
In patients with renal impairment, drugs undergo significant changes in their pharmacokinetics, which require dosage adjustments to ensure safe and effective therapy.
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
80
01:20Desensitization and Tachyphylaxis
1.7K
Tachyphylaxis is described as a rapid decrease in response to a drug after repeated or continuous administration of the same drug dose. It is a phenomenon where the body becomes less responsive to a particular substance or intervention over time, requiring higher doses or stronger interventions to achieve the same effect. It results from adaptive changes in the body's receptors, signaling pathways, or physiological processes that occur in response to prolonged exposure to a stimulus.
1.7K
01:21Smooth Endoplasmic Reticulum
5.7K
Smooth endoplasmic reticulum or smooth ER is a sub-organelle with specialized functions in animal cells and plant cells. It is often associated with the tubule morphology of the endoplasmic reticulum.
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...
5.7K