Abstract
This review summarizes key knowledge regarding the development, growth, and growth disorders of the adrenal cortex from a molecular perspective. The adrenal gland consists of two distinct regions: the cortex and the medulla. During embryological development and transition to the adult adrenal gland, the adrenal cortex acquires three different structural and functional zones. Significant progress has been made in understanding the signaling and molecules involved during adrenal cortex zonation. Equally significant is the knowledge obtained regarding the action of peptide factors involved in the maintenance of zonation of the adrenal cortex, such as peptides derived from proopiomelanocortin processing, adrenocorticotropin and N-terminal proopiomelanocortin. Findings regarding the development, maintenance and growth of the adrenal cortex and the molecular factors involved has improved the scientific understanding of disorders that affect adrenal cortex growth. Hypoplasia, hyperplasia and adrenocortical tumors, including adult and pediatric adrenocortical adenomas and carcinomas, are described together with findings regarding molecular and pathway alterations. Comprehensive genomic analyses of adrenocortical tumors have shown gene expression profiles associated with malignancy as well as methylation alterations and the involvement of miRNAs. These findings provide a new perspective on the diagnosis, therapeutic possibilities and prognosis of adrenocortical disorders.
Highlights
The earliest recognizable form of the adrenal gland occurs 28-30 days postconception (DPC) as the adrenogonadal primordium (AGP), which is detected by the expression of steroidogenic factor 1 (SF-1), known as NR5A1 [1]
The fetal zone (FZ) consists of large eosinophilic cells with characteristics typical of steroidogenic cells, whereas the definitive zone (DZ) consists of small, compact basophilic
It interacts with SF-1 and LRH-1, and functional studies have shown that DAX-1 is a repressor of SF-1 and LRH-1 [10,11]
Summary
The regulation of Dax1 expression maintains the balance between progenitor stem cell renewal and adrenocortical differentiation, which involves different factors such as SF-1, ACTH and Wnt signaling [15]. Through the control of WT1, GATA4, GLI1, and TCF21 expression in the mouse adrenal cortex, progenitor/stem populations can provide and maintain steroidogenic cells in the adrenal gland [24].
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