Endocrine Abstracts

In humans, adrenarche represents a unique endocrine process manifest by the development of the adrenal zonal reticularis and its production of a group of steroids often called the ‘adrenal androgens’. The physiologic manifestations of adrenarche are reflected by enhanced dehydroepiandrosterone sulfate (DHEA-S) production and the onset of adult body odor, mild acne and axillary and/or pubic hair. Clinically, the early rise in adrenal androgens is termed premature adrenarche (PremA) and can be characterized by pubic hair development before age 8/9 years in girls/boys. PremA has gained attention in recent years as a possible precursor for hyperandrogenic and insulin-resistant states in adolescence and adulthood. Interestingly, the adrenarche biochemical marker DHEA-S has little or no androgenic activity suggesting that its peripheral conversion or adrenal production of more bioactive steroids is key to the phenotypic effects seen during this process. We have applied histologic, genomic and steroid biome analyses to better define the adrenal changes associated with and the steroids produced during adrenarche. Transcriptome comparison of adrenal zona fasciculata and reticularis defined a unique steroidogenic phenotype for both zones. The expression pattern of key steroidogenic enzymes particularly tracked with adrenarche reticularis expansion and their expression pattern explains the onset of DHEA-S production. Analysis of steroids in children progressing through adrenarche and children with PremA demonstrated changes, not only in DHEA-S, but broad-based alterations in the steroid metabolome coinciding with an apparent infant to adolescent reshaping of the adrenal glands. The steroid changes observed during adrenarche were also significantly exaggerated in Prem-A. This presentation will provide an update of findings related to the intra-adrenal changes seen and the steroids produced during adrenarche.