Division of Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, Bern 3010, Switzerland.
Department for BioMedical Research, University Hospital Inselspital, University of Bern, Bern 3010, Switzerland.
Endocrinology. 2024 Jan 16;165(3). doi: 10.1210/endocr/bqae014.
Cholesterol is the precursor of all steroids, but how cholesterol flux is controlled in steroidogenic tissues is poorly understood. The cholesterol exporter ABCG1 is an essential component of the reverse cholesterol pathway and its global inactivation results in neutral lipid redistribution to tissue macrophages. The function of ABCG1 in steroidogenic tissues, however, has not been explored. To model this, we inactivated Abcg1 in the mouse adrenal cortex, which led to an adrenal-specific increase in transcripts involved in cholesterol uptake and de novo synthesis. Abcg1 inactivation did not affect adrenal cholesterol content, zonation, or serum lipid profile. Instead, we observed a moderate increase in corticosterone production that was not recapitulated by the inactivation of the functionally similar cholesterol exporter Abca1. Altogether, our data imply that Abcg1 controls cholesterol uptake and biosynthesis and regulates glucocorticoid production in the adrenal cortex, introducing the possibility that ABCG1 variants may account for physiological or subclinical variation in stress response.
胆固醇是所有类固醇的前体，但类固醇生成组织中胆固醇通量如何被控制还知之甚少。胆固醇外排蛋白 ABCG1 是逆向胆固醇途径的重要组成部分，其全局失活会导致中性脂质重新分配到组织巨噬细胞中。然而，ABCG1 在类固醇生成组织中的功能尚未被探索。为了模拟这种情况，我们在小鼠肾上腺皮质中使 Abcg1 失活，导致与胆固醇摄取和从头合成相关的转录物在肾上腺中特异性增加。Abcg1 失活不影响肾上腺胆固醇含量、分区或血清脂质谱。相反，我们观察到皮质酮产生适度增加，但这不能通过功能相似的胆固醇外排蛋白 Abca1 的失活来重现。总的来说，我们的数据表明 ABCG1 控制胆固醇摄取和生物合成，并调节肾上腺皮质中的糖皮质激素产生，这提示 ABCG1 变体可能与应激反应的生理或亚临床变化有关。
