Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) inhibit the apoptosis in human peripheral blood lymphocytes.
BACKGROUND
Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) are the major steroid hormones secreted by the adrenal gland. Administration of DHEA has been reported to have beneficial effects on aging, diabetes, and atherosclerosis. Apoptosis is a normal physiologic process that occurs during embryonic development as well as in the maintenance of tissue homeostasis. In this study, we examined the suppressive effect of DHEA(S) on staurosporine-induced apoptosis in human peripheral blood lymphocytes (PBL).


METHODS
Apoptosis was induced in human PBL with staurosporine and measured by flow cytometry utilizing Annexin V and propidium iodide (PI) staining. The quantity of FITC+/PI- cells corresponded to early apoptosis, while that of FITC+/PI+ cells corresponded to late apoptosis or secondary necrosis.


RESULTS
The fraction of staurosporine-induced early apoptosis but not that of secondary necrosis in PBL was reduced by the treatment with either DHEA or DHEAS. Furthermore, this apoptosis was neither associated with androgen receptor (AR) nor with estrogen receptor (ER).


CONCLUSIONS
This is the first study showing that DHEA(S) inhibits apoptosis in human PBL through a mechanism independent of either ARs or ERs. DHEA(S) may be a promising chemopreventive drug for aging, diabetes, and atherosclerosis.
Takahashi
Hirokazu
H
The Third Department of Internal Medicine, School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa, Yokohama, Japan. hirokazu@med.yokohama-cu.ac.jp
Nakajima
Atsushi
A
Sekihara
Hisahiko
H
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology*; D005434:Flow Cytometry; D005485:Flutamide / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D019311:Staurosporine / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology
D013629:Tamoxifen; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D005485:Flutamide; D019311:Staurosporine