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Review
. 2009 Mar 25;301(1-2):83-8.
doi: 10.1016/j.mce.2008.10.019. Epub 2008 Nov 1.

DHEA metabolism in prostate: For better or worse?

Julia T Arnold  1
Affiliations
Review

DHEA metabolism in prostate: For better or worse?

Julia T Arnold. Mol Cell Endocrinol. .

Abstract

Dehydroepiandrosterone (DHEA) is commonly used in the USA as a nutritional supplement for antiaging, metabolic support or other uses. Investigations into understanding the effects of DHEA on human prostate cancer progression have posed more questions than answers and highlight the importance of communications between stromal and epithelial tuoitiuot elements within the prostate that contribute to the regulation of DHEA metabolism. Intracrine metabolism of DHEA to androgens (A) and/or estrogens (E) may occur in one cell compartment (stromal) which may release paracrine hormones or growth/inhibitory factors to the epithelial cells. Alternatively no metabolism of DHEA may occur, resulting in no harmful consequences of high levels of DHEA in prostate tissues. We herein review the tissue components involved and interactions with the prohormone, DHEA and/or resulting metabolites, including dihydrotestosterone (DHT) or 17beta-estradiol (E(2)) in an in vitro model of endocrine-immune-paracrine interactions within the prostate. This work raises questions and hypotheses concerning the role of DHEA in prostate in normal tissues, vs. preneoplastic tissues.

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Figures

Figure 1
Figure 1. Endo-Immuno-Paracrine influences of DHEA effects on prostate epithelium depends on prostate hormonal microenvironment metabolism and local microenvironment
The complexity of the prospective effects of DHEA in prostate tissues includes such contributing factors as 1- the possible metabolism of DHEA to androgenic or estrogenic ligands. Androgen Receptor ligands include androstenedione, T and DHT. DHEA is a ligand for the mutant AR as exemplified in the LNCaP cell line. Estrogenic metabolites such as 17β Estradiol, 7-OH-DHEA and serve as ligands for the ERβ. 2- the potential contribution of inflammatory cytokines may increased steroid metabolic enzyme levels or activity; 3- the stromal and epithelial cell components including their cross-talk, 4- the AR and ERβ (or ERα in stromal cells) and downstream effectors; 5- the hormone-induced paracrine signaling; and 6- the importance of the stromal component (normal vs. reactive) as a basis for the differences in the metabolism of DHEA.
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