Dehydroepiandrosterone Sulfate (DHEAS)

DHEA and DHEAS Synthesis

DHEA and DHEAS are synthesized in the body through a series of enzymatic reactions. The synthesis of DHEA and DHEAS primarily occurs in the adrenal glands, although other tissues such as the gonads and brain also contribute to their production.

The biosynthesis of DHEA starts from cholesterol, which serves as the precursor molecule. Cholesterol is converted to pregnenolone through a series of enzymatic reactions involving the cytochrome P450 enzyme system. Pregnenolone is then converted to DHEA through the action of the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD). This conversion occurs in the smooth endoplasmic reticulum of adrenal cells. Once DHEA is formed, it can undergo further metabolism. In the adrenal glands, DHEA can be sulfated to form DHEAS. This sulfation process is catalyzed by the enzyme sulfotransferase. DHEAS is the most abundant circulating steroid in humans and serves as a storage form of DHEA. It exhibits immunostimulatory properties and counteracts the effects of glucocorticoids. The balance between cortisol and DHEAS levels is important as they have opposing actions. DHEA also serves as a precursor for other hormones such as androstenedione, testosterone, and estrogen.

Figure 1. Schematic representation of pathway for DHEA and DHEAS synthesis.
(Source: Tomo, S. et al., 2021)

DHEA and DHEAS in Health and Disease

Changes in DHEA and DHEAS levels have been associated with various diseases.

• Aging and Age-Related Diseases
  DHEA and DHEAS levels decline with age, and this decline has been associated with age-related diseases such as cardiovascular disease, frailty, and mortality. Lower DHEA and DHEAS levels in older individuals have been linked to increased risks of coronary heart disease and overall mortality. The decline in DHEAS levels, coupled with relatively stable cortisol levels, contributes to hormonal imbalances associated with aging.
• Inflammatory Conditions
  Decreased DHEAS levels have been observed in inflammatory conditions such as rheumatoid arthritis, systemic lupus erythematosus, progressive systemic sclerosis, and inflammatory bowel disease. These conditions are characterized by dysregulated immune responses, and low DHEAS levels may contribute to altered immune function.
• Polycystic Ovarian Syndrome (PCOS)
  PCOS is a hormonal disorder in women, and elevated levels of DHEA have been observed in this condition. Excess DHEA production by the adrenal glands contributes to the hormonal imbalances seen in PCOS.
• Adrenal Insufficiency
  Adrenal insufficiency occurs when the adrenal glands do not produce sufficient amounts of hormones. DHEA and DHEAS levels are often used as markers to evaluate adrenal function and diagnose adrenal insufficiency.
• Depression and Mood Disorders
  DHEA supplementation has been investigated as a potential treatment for depression and mood disorders. Some studies suggest that DHEA may have antidepressant effects, although further research is needed to determine its efficacy and mechanisms of action.