Biological functions and use of Dehydroepiandrosterone (DHEA)

Dehydroepiandrosterone (DHEA) and its sulfate ester, DHEAS, are the most abundant steroids circulating in human blood. They are mainly produced in the adrenals, and are converted into potent androgens and/or estrogens in peripheral tissues. DHEA is also produced in the brain, acting as a neurosteroid. 

Discovery 

DHEA was first discovered in human urine in 1931 and was isolated from human blood in 1954.

Structure 

DHEA is a major C19 steroid produced mainly by the adrenal cortex.

Properties 

Molecular formula: C19H28O2, Mr 288, Melting point: 140–141°C. Synthesis and release The adrenal cortex is the main production site of DHEA, which is converted to active sex hormones in peripheral target tissues. DHEA is also produced in small quantities in the testis, ovary, and brain. Following the conversion of cholesterol to pregnenolone by CYP11A (P450scc, cholesterol side-chain cleavage), pregnenolone is converted to DHEA by CYP17 (P450c17, 17α-hydroxylase, 17,20-lyase). Most DHEA is sulfated (DHEA-sulfate, DHEAS) before secretion. DHEA can be converted to androstenedione by 3β-hydroxysteroid dehydrogenase (3β-HSD), and subsequently to active androgens and estrogens.

Biological functions

Target cells/tissues and functions DHEA and DHEAS are transformed into androgens and/or estrogens in peripheral target tissues such as gonads, brain, bone, breast, skin, lymph nodes, and adipose tissue. The transformation of DHEA and DHEAS depends on the level of expression of the various steroidogenic and metabolizing enzymes in each of these peripheral tissues.

Use for diagnosis and treatment 

As compared to DHEA, serum DHEAS concentrations do not have a circadian rhythm because the plasma half-life of DHEAS is much longer. Serum DHEAS concentrations are clinically useful in the differential diagnosis of some adrenal disorders, including adrenal adenoma, adrenal carcinoma, Cushing’s syndrome, and congenital adrenal hyperplasia. DHEA has been known as an inhibitor of carcinogenesis in various organs such as the mammary gland and prostate.

DHEAS treatment is used as antiaging and antiobesity hormone therapy.Indeed, DHEA has many effects, including vasodilatory, antiaging, antiinflammatory, antiatherosclerotic, and antidepressant effects. DHEA supplementation in postmenopausal women increases bone formation and density. However, the clinical benefits and safety of DHEA are not well established.