"目录号: HY-14650
DHEA 是雄激素重要来源，是一种有效的抗细胞凋亡因子。
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生物活性
Description
DHEA is an important source ofandrogens, and is an effective antiapoptotic factor.
IC50& Target
Androgen receptor[1]
In Vitro
DHEA is an effective antiapoptotic factor, reversing the serum deprivation-induced apoptosis in prostate cancer cells (DU145 and LNCaP cell lines) as well as in colon cancer cells (Caco2 cell line). DHEA significantly reduces serum deprivation-induced apoptosis in all 3 cancer cell types, quantitated with the APOPercentage assay (apoptosis is reduced from 0.587±0.053 to 0.142±0.0016 or 0.059±0.002 after treatment for 12 hours with DHEA or NGF, respectively; n=3, P<0.01), and by flow cytometry analysis (FACS) for DU145 cells. The antiapoptotic effect of DHEA is dose dependent with an EC50 at nanomolar concentrations (EC50: 11.2±3.6 nM and 12.4±2.2 nM in DU145 and Caco2 cells, respectively)[1]. DHEA is the principal sex steroid precursor in humans and can be converted directly to androgens. DHEA (≥1 μM) causes a dose-dependent inhibition of Chub-S7 proliferation, as assessed by thymidine incorporation assays. DHEA treatment inhibits expression of the key glucocorticoid-regulating genesH6PDH(≥100 nM) andHSD11B1(≥1 μM) in differentiating preadipocytes in a dose-dependent manner. In keeping with this finding, DHEA treatment (≥1 μM) results in a marked reduction in 11β-HSD1 oxoreductase activity (≥1 μM) and a concurrent increase in dehydrogenase activity at the highest DHEA dose used (25 μM DHEA) in differentiated adipocytes[2].
In Vivo
DHEA in the diet (0.45 % w/w) of male B6 mice (groups of five mice) treated for 8 weeks led to significant decreases in body temperature compared with mice fed the control AIN-76A diet. A similar comparison indicated that control and pair-fed mice are also significantly different. Animals fed DHEA have significantly lower temperatures than mice fed the control diet 26/29 times tested; mice pair fed to those on the DHEA diet are less affected, with 8/29 values significantly lower than in mice fed AIN-76Aad libitum. The temperatures of mice fed DHEA or pair fed to DHEA are significantly different 21/29 times tested. Body weights are significantly greater in mice fed the control diet than in mice fed DHEA or pair fed to DHEA. Food intake (grams per day) from cages are averaged for each week (n=7), except for Week 9 (n=3). The amount of food intake is significantly decreased in mice fed DHEA. By design, mice pair fed to DHEA ate about the same amount. Thus, it appears that DHEA reduces body temperature by food restriction and by a separate mechanism[3].
Clinical Trial
ShangHai Ji Ai Genetics & IVF Institute
Infertility
December 2014
Phase 4
Taipei Veterans General Hospital, Taiwan-National YangMing University
Dehydroepiandrosterone-DHEAS-Gene Expression of Cumulus Cells.-Ovarian Hyper-stimulation Protocol.-Artificial Reproduction Technology.
January 2013
Phase 3
University Hospital Tuebingen
Adrenal Insufficiency
October 2003
Phase 3
Monash University
Quality of Life-Menopausal Syndrome-Libido Disorder
February 2006
Phase 3
Jed E. Rose-Duke University
Substance Withdrawal Syndrome
July 2009
Phase 2
Center for Human Reproduction
Primary Ovarian Insufficiency-Unexplained Infertility
March 2008
Phase 2-Phase 3
The Affiliated Hospital of Inner Mongolia Medical University-First Affiliated Hospital, Sun Yat-Sen University-Renmin Hospital of Wuhan University
Subfertility
February 2015
David H. Barad-Center for Human Reproduction
Premature Ovarian Failure
June 2009
Phase 2-Phase 3
Humanetics Corporation
PTSD
February 2013
Phase 2
Center for Human Reproduction-Foundation for Reproductive Medicine
Infertility-Decreased Ovarian Reserve
January 2007
Phase 2-Phase 3
Tel-Aviv Sourasky Medical Center
Hypoactive Sexual Desire Disorder
June 2005
KK Women's and Children's Hospital
Infertility-Poor Responder to IVF Treatment
February 2012
Phase 3
CHU de Quebec-Universite Laval
Skin Aging-Quality of Life
November 1, 2004
Phase 3
Virginia Center for Reproductive Medicine
Infertility
January 2010
Early Phase 1
UMC Utrecht-University Medical Center Groningen-Dutch Arthritis Association
Lupus Erythematosus, Systemic-Sjogren's Syndrome
May 2000
Phase 2
University of Nottingham
Infertility-Ovarian Aging-Diminished Ovarian Reserve (DOR)-Predicted Poor-responders
May 2012
Phase 3
University of Versailles-Association Française contre les Myopathies (AFM), Paris-Assistance Publique - Hôpitaux de Paris
Myotonic Dystrophy
November 2004
Phase 2-Phase 3
National Institute of Dental and Craniofacial Research (NIDCR)-National Institutes of Health Clinical Center (CC)
Lacrimal Apparatus Disease-Salivary Gland Disease-Sjogren's Syndrome-Xerostomia
May 1997
Phase 2
University of Michigan-Arthritis Foundation
Systemic Lupus Erythematosus
September 2003
Phase 2-Phase 3
Meir Medical Center
Ovarian Stimulation
January 2008
Helsinki University-Göteborg University-Uppsala University
Sjogren's Syndrome
February 2003
Phase 4
University of Maryland-National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type 1 Diabetes
October 2010
Early Phase 1
Université Victor Segalen Bordeaux 2
Malaria
April 2002
Phase 3
University of Aarhus
Adrenal Insufficiency
October 2001
National Institute of Mental Health (NIMH)-National Institutes of Health Clinical Center (CC)
Depressive Disorder-Mood Disorder
June 1995
Phase 2
Bayer
Libido
November 2007
Phase 2
National Center for Research Resources (NCRR)-Northwestern University-Office of Rare Diseases (ORD)
Systemic Lupus Erythematosus
August 1994
Phase 2-Phase 3
National Center for Research Resources (NCRR)-Northwestern University-Office of Rare Diseases (ORD)
Systemic Lupus Erythematosus
June 1995
Phase 2
National Center for Research Resources (NCRR)-Northwestern University-Office of Rare Diseases (ORD)
Systemic Lupus Erythematosus
March 1996
Phase 3
National Center for Research Resources (NCRR)-University of California, Los Angeles-Office of Rare Diseases (ORD)
Addison's Disease
August 1995
Phase 3
Guangzhou University of Traditional Chinese Medicine
Primary Ovarian Insufficiency
April 2016
Early Phase 1
Mayo Clinic
Hyperandrogenism
December 2006
Boston Children’s Hospital-United States Department of Defense-Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Anorexia Nervosa
April 2004
Phase 2-Phase 3
Inflabloc Pharmaceuticals
Crohn's Disease
January 2005
Phase 2
The University of Texas Medical Branch, Galveston-National Institutes of Health (NIH)
Burns
July 2002
Phase 2-Phase 3
EndoCeutics Inc.
Vaginal Atrophy
February 2014
Phase 3
Genelabs Technologies
Systemic Lupus Erythematosus
July 2003
Phase 3
Alliance for Clinical Trials in Oncology-National Cancer Institute (NCI)-Mayo Clinic
Breast Cancer-Gynecologic Cancer
July 2011
Phase 3
Genelabs Technologies
Lupus
December 2002
Phase 3
Mayo Clinic-National Cancer Institute (NCI)
Multiple Myeloma and Plasma Cell Neoplasm
August 2000
Phase 2
Boston Children’s Hospital
Anorexia Nervosa (AN)
June 2011
Phase 3
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References
