Comparative effects of DHEA vs. testosterone, dihydrotestosterone, and estradiol on proliferation and gene expression in human LNCaP prostate cancer cells

被引:91
作者
Arnold, JT
Le, H
McFann, KK
Blackman, MR
机构
[1] NIH, Endocrine Sect, Clin Invest Lab, Div Intramural Res,LCI NCCAM, Bethesda, MD 20892 USA
[2] NIH, Off Clin & Regulatory Affairs, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2005年 / 288卷 / 03期
关键词
dehydroepiandrosterone; androgen receptor; prostate-specific antigen; insulin-like growth factor axis; estrogen receptor-beta; lymph nodederived cancer of prostate;
D O I
10.1152/ajpendo.00454.2004
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Serum levels of the adrenal androgen dehydroepiandrosterone (DHEA) peak in men and women in the third decade of life and decrease progressively with age. Increasing numbers of middle-aged and older individuals consume over-the-counter preparations of DHEA, hoping it will retard aging by increasing muscle and bone mass and strength, decreasing fat, and improving immunologic and neurobehavioral functions. Because DHEA can serve as a precursor to more potent androgens and estrogens, like testosterone (T), dihydrotestosterone (DHT), and 17beta-estradiol (E-2), supplemental DHEA use may pose a cancer risk in patients with nascent or occult prostate cancer. The steroid-responsive human LNCaP prostate cancer cells, containing a functional but mutated androgen receptor (AR), were used to compare effects of DHEA with those of T, DHT, and E-2 on cell proliferation and protein and/or gene expression of AR, prostate-specific antigen (PSA), IGF-I, IGF-I receptor (IGF-IR), IGF-II, IGF-binding proteins-2, -3, and -5, (IGFBPs-2, -3, and -5), and estrogen receptor-beta (ERbeta). Cell proliferation assays revealed significant stimulation by all four steroids. DHEA-and E-2-induced responses were similar but delayed and reduced compared with that of T and DHT. All four hormones increased gene and/or protein expression of PSA, IGF-IR, IGF-I, and IGFBP-2 and decreased that of AR, ERbeta, IGF-II, and IGFBP-3. There were no significant effects of hormone treatment on IGFBP-5 mRNA. DHEA and E-2 responses were similar, and distinct from those of DHT and T, in time- and dose-dependent studies. Further studies of the mechanisms of DHEA effects on prostate cancer epithelial cells of varying AR status, as well as on prostate stromal cells, will be required to discern the implications of DHEA supplementation on prostatic health.
引用
收藏
页码:E573 / E584
页数:12
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