甲状腺激素的空间依赖组织分布由血甲状腺激素结合蛋白
Anish D Bagga1, Brian P Johnson2, Qiang Zhang3
1Emory College of Arts and Sciences, Emory University, Atlanta, GA, 30322, USA.
Pflugers Archiv : European journal of physiology
|January 3, 2025
概括
甲状腺激素结合蛋白 (THBPs),如甲状腺激素结合环球蛋白 (TBG),转激素蛋白 (TTR) 和专蛋白 (ALB),在将甲状腺激素 (THs) 输送到组织中发挥着不同的作用. 我们的模型揭示了它们对组织吸收的差异性贡献,影响了局部激素分布.
科学领域:
- 内分泌学 在内分泌学.
- 药理动力学 药理动力学
- 计算生物学 计算生物学
背景情况:
- 血甲状腺激素结合蛋白 (THBPs),包括甲状腺激素结合环球蛋白 (TBG),TTR和专蛋白 (ALB),将甲状腺激素 (THs) 运送到组织中.
- 单个THBPs在为组织吸收提供THs方面的确切作用仍然不完全理解.
研究的目的:
- 调查THBPs在为局部组织吸收提供甲状腺激素方面的不同作用.
- 阐明THBPs的空间分布和THBPs在传递THs到各种组织区的贡献.
主要方法:
- 为甲状腺激素 (THs) 开发一个基于人体生理动力学 (PBK) 的空间模型.
- 用THBPs (TBG,TTR,ALB) 模拟不同组织 perfusion 速率的TH运输和卸载.
- 分析THBPs TH卸载的空间依赖性和非线性.
主要成果:
- THBPs在肝脏中释放出相当数量的T4,但缓慢 perfused 组织中的贡献取决于T4TBG,T4TTR和T4ALB的丰度.
- THBPs有助于T3吸收或释放,基于T3TBG,T3ALB和T3TTR的丰度,无论 perfusion 速率如何.
- THBPs的TH卸载在组织内是空间依赖的,非线性,在动脉末端附近的主导是白蛋白,在静脉末端附近则是TBG.
结论:
- 所有THBPs单独足以保持均的TH组织分布.
- 在TH转运器和酶中的空间梯度可以调节TH度,从而导致不变或异质的组织水平.
- 这种建模为THBPs在局部甲状腺激素组织分布中的差异性作用提供了新的见解.
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