What is Desoxy DHEA and How Does It Work
-
Upload
denovonutrition -
Category
Documents
-
view
346 -
download
0
Transcript of What is Desoxy DHEA and How Does It Work
www.denovonutrition.com WHAT IS DESOXY DHEA AND HOW DOES IT WORK?
What is Desoxy DHEA and how does it work? By: Ben Esgro, BS,CSCS,CISSN
Desoxy (or Deoxy) DHEA is structurally similar to DHEA except for the fact that, as the name implies, an
oxygen has been removed from compound (specifically at carbon #3). Although a single deoxygenation may seem
to be an insignificant alteration, it notably alters the biological activity of the compound. Contrary to DHEA
supplementation, which has been shown to influence both estrogen and to a lesser extent testosterone
production in males [1], Deoxy DHEA acts as an anti-estrogen through unique structural interactions with the
enzyme responsible for conversion of androgens to estrogens, aromatase (CYP19). To better illustrate how Deoxy
DHEA works; let us first examine the structures of DHEA, Deoxy DHEA, Testosterone, and Androstenedione; the
latter two of which are the primary substrates aromatase acts upon to create estrogens.
DHEA DEOXY DHEA (R1=H, R2=CH3) TESTOSTERONE ANDROSTENEDIONE
To simplify our concept, let us first only focus on the rings of each of the structures illustrated above
(A,B,C, D from left to right; so the “A” ring would be the first hexagon, “B” ring the second, and so on). Notice how
they all have the same basic ring structures, 3 hexagons and one pentagon, this is the backbone structure of a
steroid hormone. When it contains 19 carbons it is referred to as an androgen, hence the reason chemical names
for androgens typically contain the word “androstene” (if there is a double bond) or “androstane” (no double
bonds). If you have ever read the label for pro-hormonal products you have undoubtedly come in contact with
these names before.
As stated previously, the principal job of aromatase is to convert androgens to estrogens, as such, it has a
high affinity for the two primary androgens Testosterone and Androstenedione. This affinity has been shown to be
heavily based upon the structure of the D ring and the planarity of the A ring [2-3]. Although the attraction is
strong between aromatase and the substrates Testosterone and Androstenedione, alternative structures can bind
the enzyme more efficiently. This concept is referred to as competitive inhibition, where an inhibiting compound
can bind to the enzyme with a greater affinity than the usual substrate thus preventing subsequent alteration to
the substrate (Testosterone in this case).
Again, it appears that A and D ring modifications are heavily influential upon the affinity of a compound to
bind to aromatase. Specifically, a 17-carbonyl structure (“D” ring modification where a carbon-oxygen double
bond is present) is required for tight binding to the active site of the enzyme [4], and 3-deoxy compounds (“A” ring
modification where oxygen has been removed) have displayed higher affinities compared to the usual androgen
substrates (Testosterone and Androstenedione) [2]. As you can see by observing the structure of Deoxy DHEA, it
possesses BOTH of these characteristics which allows it is preferentially bind to aromatase, leaving greater
circulating levels of Testosterone to exert their benefits.
www.denovonutrition.com WHAT IS DESOXY DHEA AND HOW DOES IT WORK?
BOTTOM LINE
Although Deoxy DHEA is an effective competitive inhibitor of aromatase it is not nearly as potent as
SERMs or other steroidal and non-steroidal suicide inhibitors [5]. The structure-activity relationships mentioned
are not comprehensive as there undoubtedly exist additional structural manipulations that occur to further
enhance aromatase affinity. Therefore, it is NOT an appropriate replacement to prescription compounds when
heavy aromatase inhibition is required. It does however, offer a cost-effective, safe, and legal method of estrogen
management as validated by independent lab tests and selected in vitro data.
1. Paul M. Coates, M.R.B., Gordon M. Cragg, Mark Levine, Joel Moss, Jeffrey D. White, ed. Encyclopedia of Dietary Supplements. 2005, Marcel Dekker: New York, NY.
2. Cepa, M.M.D.S., et al., Structure−Activity Relationships of New A,D-Ring Modified Steroids as Aromatase Inhibitors: Design, Synthesis, and Biological Activity Evaluation. Journal of Medicinal Chemistry, 2005. 48(20): p. 6379-6385.
3. Numazawa, M., et al., Role of Hydrophilic Interaction in Binding of Hydroxylated 3-Deoxy C19 Steroids to the Active Site of Aromatase. Journal of Medicinal Chemistry, 2001. 44(24): p. 4277-4283.
4. Numazawa, M., et al., Synthesis and biochemical studies of 16- or 19-substituted androst-4-enes as aromatase inhibitors. Journal of Medicinal Chemistry, 1991. 34(8): p. 2496-2504.
5. Numazawa, M., M. Nagaoka, and N. Sohtome, Aromatase Reaction of 3-Deoxyandrogens: Steric Mode of the C-19 Oxygenation and Cleavage of the C10−C19 Bond by Human Placental Aromatase†. Biochemistry, 2005. 44(32): p. 10839-10845.