Β-catenin in adrenal zonation and disease. (15th February 2021)

• Record Type: Journal Article
• Authors: Little, Donald W.; Dumontet, Typhanie; LaPensee, Christopher R.; Hammer, Gary D.
• Is Part Of: Molecular and cellular endocrinology. Volume 522(2021)
• Publication Date: 2021-02-15
• Subjects: Wnt/β-catenin -- Adrenal cortex -- Adrenocortical zonation -- Adrenal cancer -- Regeneration -- Steroidogenesis -- Hyperplasia; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2020.111120
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: 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. Highlights: Wnt/β-catenin signaling is a critical mediator of adrenocortical zonation, regeneration, development, and homeostasis. Capsule-derived ligands activate and maintain cortical β-catenin activation. Wnt/β-catenin signaling exists in a centripetal zG-to-zF gradient that is regulated by ZNRF3, PKA, and EZH2. Alterations in Wnt/β-catenin pathway components are highly prevalent in adrenal disease, accounting for 40% of ACC cases.