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.