Dehydroepiandrosterone sulfate (DHEAS)

Dehydroepiandrosterone sulfate (DHEAS) is the most abundant circulating steroid hormone in humans and serves primarily as a prohormone reservoir for the production of potent androgens and estrogens in peripheral tissues. Synthesized predominantly in the adrenal cortex under the regulation of adrenocorticotropic hormone (ACTH), DHEAS levels peak in early adulthood and decline significantly with age, a process often associated with the physiological decline of the adrenal zone reticularis. Beyond its role in steroidogenesis, DHEAS is a recognized neurosteroid that influences neuronal excitability and synaptic plasticity through its interactions with GABAA, NMDA, and Sigma-1 receptors. In clinical practice, DHEAS is a crucial biomarker for evaluating adrenal function and diagnosing conditions such as polycystic ovary syndrome (PCOS), adrenal tumors, and hyperandrogenism. While synthetic DHEAS (prasterone) is used to treat vaginal atrophy and is studied for adrenal insufficiency, its systemic use remains carefully monitored due to potential side effects like virilization and the risk of promoting hormone-sensitive malignancies.

Other names

Prasterone sulfateDHEA-S3β-Hydroxy-5-androsten-17-one sulfateDehydroepiandrosterone 3-sulfatePrasterone sodium sulfate

Dehydroepiandrosterone sulfate (DHEAS) serves as a circulating reservoir for the intracrine synthesis of active androgens and estrogens through conversion by steroid sulfatase (STS) and 3β-hydroxysteroid dehydrogenase. It also functions as a neurosteroid that modulates central nervous system activity by acting as a negative allosteric modulator of GABAA receptors and a positive allosteric modulator of NMDA receptors. Furthermore, it acts as an endogenous agonist at the Sigma-1 receptor, which is implicated in neuroprotective and anti-inflammatory signaling pathways.