Dehydroepiandrosterone (DHEA)--a precursor steroid or an active hormone in human physiology.
BACKGROUND
The circulation of large amounts of dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEA-S) suggests a physiological role in human physiology. In the central nervous system, DHEA is considered a neurosteroid with a wide range of functions.


OBJECTIVE
The goal of this review is to discuss metabolism, biochemical, and physiological mechanism of DHEA action and the potential role of DHEA in aging and in ameliorating a host of pathological conditions, associated with aging.


METHODS
We examined preclinical and clinical data reported in various studies from the available literature concerning the effects of DHEA in normal and pathological conditions.


METHODS
Data reported in the literature were analyzed, reviewed, and discussed.


RESULTS
DHEA mediates its action via multiple signaling pathways involving specific membrane receptors and via transformation into androgen and estrogen derivatives (e.g., androgens, estrogens, 7α and 7β DHEA, and 7α and 7β epiandrosterone derivatives) acting through their specific receptors. These pathways include: nitric oxide synthase activation, modulation of γ-amino butyric acid receptors, N-methyl D-aspartate, receptors sigma receptors (Sigma-1), differential expression of inflammatory factors, adhesion molecules and reactive oxygen species, among others. Clinical and epidemiological studies suggested that low DHEA levels might be associated with ischemic heart disease, endothelial dysfunction, atherosclerosis, bone loss, inflammatory diseases, and sexual dysfunction. Most importantly, no significant adverse or negative side effects of DHEA were reported in clinical studies of men and women.


CONCLUSIONS
DHEA modulates endothelial function, reduces inflammation, improves insulin sensitivity, blood flow, cellular immunity, body composition, bone metabolism, sexual function, and physical strength in frailty and provides neuroprotection, improves cognitive function, and memory enhancement. DHEA possesses pleiotropic effects and reduced levels of DHEA and DHEA-S may be associated with a host of pathologies; however, the clinical efficacy of DHEA supplementation in ameliorating patho-physiological symptoms remains to be evaluated.
Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA. atraish@bu.edu
Abdulmaged M
AM
Traish
H Paco
HP
Kang
Farid
F
Saad
Andre T
AT
Guay
D000375:Aging / Q000502:physiology; D000818:Animals; D001823:Body Composition / Q000502:physiology; D001842:Bone and Bones / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000503:physiopathology; D003687:Dehydroepiandrosterone / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism; D003863:Depression / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D012725:Sexual Behavior / Q000502:physiology; D012867:Skin / Q000378:metabolism
D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate