PMID- 15536203
OWN - NLM
STAT- MEDLINE
DCOM- 20050426
LR  - 20131121
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 288
IP  - 3
DP  - 2005 Mar
TI  - Comparative effects of DHEA vs. testosterone, dihydrotestosterone, and estradiol 
      on proliferation and gene expression in human LNCaP prostate cancer cells.
PG  - E573-84
AB  - 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.
FAU - Arnold, Julia T
AU  - Arnold JT
AD  - 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.gov
FAU - Le, Hanh
AU  - Le H
FAU - McFann, Kimberly K
AU  - McFann KK
FAU - Blackman, Marc R
AU  - Blackman MR
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20041109
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 2)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 3)
RN  - 0 (Receptors, Androgen)
RN  - 0 (Testosterone Congeners)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - 3XMK78S47O (Testosterone)
RN  - 459AG36T1B (Dehydroepiandrosterone)
RN  - 4TI98Z838E (Estradiol)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 67763-97-7 (Insulin-Like Growth Factor II)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
SB  - IM
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Cell Proliferation/*drug effects
MH  - Dehydroepiandrosterone/*pharmacology
MH  - Dihydrotestosterone/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Estradiol/*pharmacology
MH  - Estrogen Receptor beta/genetics
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Humans
MH  - Insulin-Like Growth Factor Binding Protein 2/genetics
MH  - Insulin-Like Growth Factor Binding Protein 3/genetics
MH  - Insulin-Like Growth Factor I/genetics
MH  - Insulin-Like Growth Factor II/genetics
MH  - Male
MH  - Polymerase Chain Reaction
MH  - Prostate-Specific Antigen/genetics/metabolism
MH  - Prostatic Neoplasms/genetics/metabolism/pathology
MH  - Receptor, IGF Type 1/genetics/metabolism
MH  - Receptors, Androgen/genetics/metabolism
MH  - Testosterone/pharmacology
MH  - Testosterone Congeners/pharmacology
EDAT- 2004/11/13 09:00
MHDA- 2005/04/27 09:00
CRDT- 2004/11/13 09:00
PHST- 2004/11/13 09:00 [pubmed]
PHST- 2005/04/27 09:00 [medline]
PHST- 2004/11/13 09:00 [entrez]
AID - 00454.2004 [pii]
AID - 10.1152/ajpendo.00454.2004 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2005 Mar;288(3):E573-84. doi: 
      10.1152/ajpendo.00454.2004. Epub 2004 Nov 9.