Doctoral Program in Cancer Biology, USA.
Training Program in Organogenesis, Center for Cell Plasticity and Organ Design, USA; Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, USA.
Mol Cell Endocrinol. 2021 Feb 15;522:111120. doi: 10.1016/j.mce.2020.111120. Epub 2020 Dec 16.
The Wnt signaling pathway is a critical mediator of the development and maintenance of several tissues. The adrenal cortex is highly dependent upon Wnt/β-catenin signaling for proper zonation and endocrine function. Adrenocortical cells emerge in the peripheral capsule and subcapsular cortex of the gland as progenitor cells that centripetally differentiate into steroid hormone-producing cells of three functionally distinct concentric zones that respond robustly to various endocrine stimuli. Wnt/β-catenin signaling mediates adrenocortical progenitor cell fate and tissue renewal to maintain the gland throughout life. Aberrant Wnt/β-catenin signaling contributes to various adrenal disorders of steroid production and growth that range from hypofunction and hypoplasia to hyperfunction, hyperplasia, benign adrenocortical adenomas, and malignant adrenocortical carcinomas. Great strides have been made in defining the molecular underpinnings of adrenocortical homeostasis and disease, including the interplay between the capsule and cortex, critical components involved in maintaining the adrenocortical Wnt/β-catenin signaling gradient, and new targets in adrenal cancer. This review seeks to examine these and other recent advancements in understanding adrenocortical Wnt/β-catenin signaling and how this knowledge can inform therapeutic options for adrenal disease.
Wnt 信号通路是多种组织发育和维持的关键介质。肾上腺皮质对于 Wnt/β-catenin 信号的适当分区和内分泌功能高度依赖。肾上腺皮质细胞作为祖细胞出现在腺体的外周囊和皮质下区，它们向心性分化为三个功能不同的同心区的类固醇激素产生细胞，对各种内分泌刺激反应强烈。Wnt/β-catenin 信号介导肾上腺皮质祖细胞的命运和组织更新，以维持整个生命过程中的腺体。异常的 Wnt/β-catenin 信号导致各种类固醇产生和生长的肾上腺紊乱，范围从功能低下和发育不良到功能亢进、增生、良性肾上腺皮质腺瘤和恶性肾上腺皮质癌。在定义肾上腺皮质的稳态和疾病的分子基础方面已经取得了很大进展，包括囊和皮质之间的相互作用、维持肾上腺皮质 Wnt/β-catenin 信号梯度的关键成分，以及肾上腺癌的新靶点。本文旨在探讨这些和其他关于理解肾上腺皮质 Wnt/β-catenin 信号的最新进展，以及这些知识如何为肾上腺疾病的治疗选择提供信息。
