脂滴在类固醇激素合成中的作用及药物对脂滴与激素合成的影响

The Role of Lipid Droplets in Steroid Hormone Synthesis and the Effects of Drugs on Lipid Droplets and Hormone Synthesis

摘要

类固醇激素的合成以胆固醇为起始底物，主要在线粒体和内质网中进行。脂滴作为细胞内重要的能量储存细胞器，其动态转换对维持细胞内脂质稳态具有重要作用。在类固醇激素合成细胞中，脂滴分解产生的胆固醇是类固醇激素合成的重要底物来源，其动态分布和数量变化可影响线粒体和内质网的功能；同时，多种参与调控脂滴形成、分解及功能稳态的蛋白质，不仅可维持细胞内脂滴的动态平衡，还参与类固醇激素合成的调控过程。临床应用中，他汀类、前蛋白转化酶枯草溶菌素 9 抑制剂等降脂药物，以及糖皮质激素、口服避孕药等外源性激素类药物可导致部分患者发生体内激素分泌异常。综述脂滴对类固醇激素合成的影响，以期为深入理解细胞内脂质稳态与类固醇激素合成的关联提供参考。

Abstract

Steroid hormone synthesis begins with cholesterol as the primary substrate, and occurs mainly in mitochondria and endoplasmic reticulum. As important organelles for energy storage in cells, lipid droplets play a crucial role in maintaining intracellular lipid homeostasis through their dynamic turnover. In steroidogenic cells, cholesterol derived from lipid droplet catabolism is an important source of substrates for steroid hormone synthesis, and the dynamic distribution and quantity changes of lipid droplets can influence the functions of mitochondria and endoplasmic reticulum. Meanwhile, various proteins involved in regulating the formation, catabolism and functional homeostasis of lipid droplets not only maintain the dynamic balance of intracellular lipid droplets, but also participate in the regulation of steroid hormone synthesis. In the clinical application of lipid-lowering drugs such as statins and proprotein convertase subtilisin/kexin type 9 inhibitors, as well as exogenous hormonal drugs including glucocorticoids and oral contraceptives, some patients may exhibit abnormal steroid hormone secretion. This review summarizes the effects of lipid droplets on steroid hormone synthesis, aiming to provide some reference for further understanding the association between intracellular lipid homeostasis and steroid hormone synthesis.

关键词

脂滴 / 类固醇激素合成 / 脂滴形成 / 脂解 / 胆固醇 / 脂质稳态

Key words

lipid droplet / steroid hormone synthesis / lipid droplet formation / lipolysis / cholesterol / lipid homeostasis

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基金资助

国家自然科学基金资助项目(82174072)