Adrenal androgens, adrenarche, and zona reticularis: A human affair?

In humans, reticularis cells of the adrenal cortex fuel the production of androgen steroids, constituting the driver of numerous morphological changes during childhood. These steps are considered a precocious stage of sexual maturation and are grouped under the term adrenarche. This review describes the molecular and enzymatic characteristics of the zona reticularis, along with the possible signals and mechanisms that control its emergence and the associated clinical features. We investigate the differences between species and discuss new studies such as genetic lineage tracing and transcriptomic analysis, highlighting the rodent inner cortex's cellular and molecular heterogeneity. The recent development and characterization of mouse models deficient for Prkar1a presenting with adrenocortical reticularis-like features prompt us to review our vision of the mouse adrenal gland maturation. We expect these new insights will help increase our understanding of the adrenarche process and the pathologies associated with its deregulation.

Automated summary

This review discusses the role of reticularis cells of the adrenal cortex in producing androgen steroids in humans, driving morphological changes during childhood and contributing to the precocious stage of sexual maturation known as adrenarche. It also explores the molecular and enzymatic characteristics of the zona reticularis, as well as new studies using genetic lineage tracing and transcriptomic analysis to investigate cellular and molecular heterogeneity in rodents. Recent findings from mouse models deficient for Prkar1a with adrenocortical reticularis-like features prompt a reexamination of the maturation of the mouse adrenal gland, which is expected to further enhance our understanding of the adrenarche process and associated pathologies.