Endogenous DHEA is a complex hormone, and researchers still have much to discover in regards to its physiologic effects in males and females. Less is known regarding the mechanisms of action of exogenously administered DHEA.
CNS actions: Both DHEA and DHEAS may be synthesized de-novo by the central nervous system, and concentrations of DHEA and DHEAS are higher in the brain than in other organs. The two neurohormones appear to have excitatory activity at both GABA and NMDA receptors.(1)
Dermatologic actions after burn injury: Animal studies have suggested that DHEA and DHEAS expedite the re-epithelialization of donor skin-graft sites.(4)
Endocrine actions: Endogenous DHEA is synthesized by the conversion of cholesterol via CYP11A1 to pregnenolone, followed by CYP17 conversion to DHEA and then to DHEAS via dehydroepiandrosterone sulfatransferase. The synthesis of DHEA occurs exclusively in the adrenal cortex in women, while in men 10—25% of DHEA is synthesized by the testes and roughly 80% of the DHEA comes from the adrenal glands. DHEA is converted via hydrosteroid dehydrogenases and aromatase into androstenedione, testosterone, and estradiol by peripheral tissues. DHEA is of only minor importance as an androgenic substance itself. The production rate of DHEA by the body changes dramatically throughout life, typically peaking at adrenarche, the adrenal contribution to the onset of puberty. In males, DHEA serum levels are high in neonates right after birth, rapidly fall within 5 months, then begin to rise at the age of 9 years. Endogenous DHEA concentration then peaks again in males at roughly the 20th—30th years of life. In females, DHEA serum levels are high in neonates right after birth, rapidly fall within 5 months, then begin to rise at the age of 7 years. Endogenous DHEA concentration then peaks again in females at roughly the 20th and 40th year of life. DHEA levels decline steadily after the fifth decade in both males and females. DHEAS concentrations in males and females follow similar patterns. The administration of DHEA supplements results in different hormonal concentration changes in males and females; the actions are dependent on the dose, formulation and route of administration, and age of the person receiving the DHEA.(1)
Hemostasis: Inhibition of platelet aggregation by exogenous DHEA has been demonstrated in vivo in humans; DHEA either prolonged or completely inhibited the rate of arachidonate-stimulated platelet aggregation after 14 days of administration. The degree of inhibition of platelet aggregation was noted to be time and dose dependent.(5)
Immunologic actions: Because SLE occurs more frequently in women than men and because SLE is known to worsen during pregnancy, a hormonal etiology is suspected for this disease. DHEA up-regulates interleukin-2 (IL-2) production by T-lymphocytes in murine lupus models and reverses the clinical autoimmune disease. Lower endogenous levels of DHEA and DHEAS have been noted in both male and female patients with lupus at the time of diagnosis. Chronic corticosteroid treatment, which may cause adrenal atrophy, contributes to reduced DHEA levels in these patients. Supplementation of DHEA in SLE may augment immune system activity and potentially offset the undesired effects of chronic corticosteroid use in these patients.(6) Exact mechanisms of DHEA on immune function are not yet clear. DHEA has been shown to increase the numbers of natural killer cells in aging women. Serum DHEA levels are observed to be reduced in patients with AIDS or age-related immunodeficiency, suggesting that DHEA may serve as a marker of the integrity of the immune system. No studies to date have shown that DHEA supplementation augments currently available therapies for AIDS.(1)
Leave a Reply