| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on March 29, 2005
Accepted on June 24, 2005
Department of Molecular Endocrinology, Merck Research Laboratories, West Point, PA 19486, U.S.A.; Centro de Investigación Básica. Merck, Sharp & Dohme de España. Josefa Valcárcel 38, Madrid 28027 Spain
* To whom correspondence should be addressed. E-mail: fang_chen{at}merck.com.
Dehydroepiandrosterone (DHEA) exhibits peak adrenal secretion in the fetus at term and around age 30 in the adult. Levels then progressively decline, which is associated with decreased levels of testosterone (T), dihydrotestosterone (DHT) and estrogen (E2) in peripheral tissues. DHEA supplementation in postmenopausal women increases bone formation and density, an effect mainly attributed to peripheral conversion to sex hormones. In this study, we tested DHEA for direct effects on the androgen (AR) and estrogen (ER) receptors. DHEA bound to AR with a Ki of 1 µM, which was associated with AR transcriptional antagonism on both the MMTV and PSA promoters, much like the effects of bicalutamide. Unlike bicalutamide, DHEA stimulated, rather than inhibited, LNCaP cell growth, suggesting possible interaction with other hormone receptors. Indeed DHEA bound to ER
and 
, with Kis of 1.1 and 0.5 µM, respectively. Despite the similar binding affinities, DHEA showed preferential agonism of ER with an EC50 of 
200 nM and maximal activation at 1 µM. With ER we found 30-70% agonism at 5 µM, depending on the assay. Physiological levels of DHEA are 30 nM and up to 90 nM in the prostate. DHEA at 30 nM is actually sufficient to activate ER transcription to the same degree as E2 at its circulating concentration, and additive effects are seen when the two were combined. Taken together, DHEA has the potential for physiologically-relevant direct activation of ER. With peak levels at term and age 30, there is also a potential for antagonist effects on AR and partial agonism of ER.
This article has been cited by other articles:
 |
|
 |
|
  A. E. M. Newman, D. S. Pradhan, and K. K. Soma Dehydroepiandrosterone and Corticosterone Are Regulated by Season and Acute Stress in a Wild Songbird: Jugular Versus Brachial Plasma Endocrinology, May 1, 2008; 149(5): 2537 - 2545. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Davis, S. M. Shah, D. P. McKenzie, J. Kulkarni, S. L. Davison, and R. J. Bell Dehydroepiandrosterone Sulfate Levels Are Associated with More Favorable Cognitive Function in Women J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 801 - 808. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Roy, M. Alevizaki, and I. Huhtaniemi In vitro bioassays for androgens and their diagnostic applications Hum. Reprod. Update, January 1, 2008; 14(1): 73 - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Panjari and S. R. Davis DHEA therapy for women: effect on sexual function and wellbeing Hum. Reprod. Update, May 1, 2007; 13(3): 239 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Davis, S. L. Davison, S. Donath, and R. J. Bell Self-reported Sexual Function in Women and Androgen Levels--Reply JAMA, November 2, 2005; 294(17): 2168 - 2168. [Full Text] [PDF]
|
|
|
|
|
|
J. T. Arnold and M. R. Blackman Does DHEA Exert Direct Effects on Androgen and Estrogen Receptors, and Does It Promote or Prevent Prostate Cancer? Endocrinology, November 1, 2005; 146(11): 4565 - 4567. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
