Adrenopause.
Dehydroepiandrosterone(DHEA) and DHEA-S are steroids that are abundantly produced by the adrenal gland. Plasma concentrations of DHEA and DHEA-S increase during adrenarche but decrease steadily after puberty. Although DHEA and DHEA-S have few intrinsic androgenic actions, they have recently attracted widespread attention due to their beneficial anti-aging effects. We clarified the beneficial effects of DHEA as an anti-aging steroid with regard to its stimulation of the immune system and its anti-diabetes, anti-atherosclerosis, anti-dementia (neurosteroid), anti-obesity and anti-osteoporosis effects. There are two possible biochemical and molecular mechanisms: direct action via the DHEA receptor on the target gene; and indirect action. We identified a high affinity of DHEA binding in human T-lymphocytes by searching for the target genes that are induced in activated T-lymphocytes in the presence of DHEA, determined the gene sequence and named DHEA-induced dual p38-specific phosphatase (DDSP). DDSP transgenic mice have been created to identify the anti-aging effects of DDSP. The conversion of DHEA to estrone by cytochrome P450 aromatase in primary cultured human osteoblasts was clarified. We are currently undertaking an open trial of DHEA replacement therapy.
Nawata
Hajime
H
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. nawata@intmed3.med.kyushu-u.ac.jp
Yanase
Toshihiko
T
Goto
Kiminobu
K
Okabe
Taijiro
T
Nomura
Masatoshi
M
Ashida
Kenji
K
Watanabe
Tetsuhiro
T
D000311:Adrenal Glands / Q000502:physiology*; D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D003687:Dehydroepiandrosterone / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism; D004703:Endocrine System / Q000502:physiology; D020249:Hormone Replacement Therapy; D006801:Humans; D017027:Protein Tyrosine Phosphatases / Q000502:physiology
D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; C500554:DDSP protein, human; D017027:Protein Tyrosine Phosphatases