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Comparative effects of DHEA vs. testosterone, dihydrotestosterone, and estradiol on proliferation and gene expression in human LNCaP prostate cancer cells.
Am J Physiol Endocrinol Metab. 2005 Mar; 288(3):E573-84.AJ

Abstract

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 (E2), 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 E2 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 E2-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 E2 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.

Authors+Show Affiliations

Endocrine Section, Laboratory of Clinical Investigation, Division of Intramural Research, NCCAM, NIH, 9 Memorial Dr., Rm 1N105, Bethesda, MD 20892-0933, USA. jarnold@mail.nih.govNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15536203

Citation

Arnold, Julia T., et al. "Comparative Effects of DHEA Vs. Testosterone, Dihydrotestosterone, and Estradiol On Proliferation and Gene Expression in Human LNCaP Prostate Cancer Cells." American Journal of Physiology. Endocrinology and Metabolism, vol. 288, no. 3, 2005, pp. E573-84.
Arnold JT, Le H, McFann KK, et al. Comparative effects of DHEA vs. testosterone, dihydrotestosterone, and estradiol on proliferation and gene expression in human LNCaP prostate cancer cells. Am J Physiol Endocrinol Metab. 2005;288(3):E573-84.
Arnold, J. T., Le, H., McFann, K. K., & Blackman, M. R. (2005). Comparative effects of DHEA vs. testosterone, dihydrotestosterone, and estradiol on proliferation and gene expression in human LNCaP prostate cancer cells. American Journal of Physiology. Endocrinology and Metabolism, 288(3), E573-84.
Arnold JT, et al. Comparative Effects of DHEA Vs. Testosterone, Dihydrotestosterone, and Estradiol On Proliferation and Gene Expression in Human LNCaP Prostate Cancer Cells. Am J Physiol Endocrinol Metab. 2005;288(3):E573-84. PubMed PMID: 15536203.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative effects of DHEA vs. testosterone, dihydrotestosterone, and estradiol on proliferation and gene expression in human LNCaP prostate cancer cells. AU - Arnold,Julia T, AU - Le,Hanh, AU - McFann,Kimberly K, AU - Blackman,Marc R, Y1 - 2004/11/09/ PY - 2004/11/13/pubmed PY - 2005/4/27/medline PY - 2004/11/13/entrez SP - E573 EP - 84 JF - American journal of physiology. Endocrinology and metabolism JO - Am. J. Physiol. Endocrinol. Metab. VL - 288 IS - 3 N2 - 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 (E2), 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 E2 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 E2-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 E2 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. SN - 0193-1849 UR - https://www.unboundmedicine.com/medline/citation/15536203/Comparative_effects_of_DHEA_vs__testosterone_dihydrotestosterone_and_estradiol_on_proliferation_and_gene_expression_in_human_LNCaP_prostate_cancer_cells_ L2 - http://www.physiology.org/doi/full/10.1152/ajpendo.00454.2004?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -