Anti-inflammatory Benefits of Androstenetriol (5-androstene-3 beta-7 beta-17 beta-triol, beta AET)


Androstene-3 beta-7 beta-17 beta-triol (AET) represents a key naturally occurring 7-hydroxy dehydroepiandrosterone (DHEA) metabolite. Produced from the adrenal gland, DHEA and its sulfate are the major circulating adrenal steroids in humans. Serum levels peak in young adults, but then steadily decline with age, falling over 80% by age 70. DHEA serves as a precursor of male and female sex hormones. (1, 3, 5, 6)


DHEA demonstrates a plethora of anti-aging properties in rodents, including anti-inflammatory, anti-obesity, anti-diabetic, immune enhancing activities, and opposes certain activities of endogenous glucocorticoids (GC). As the literature grew, DHEA became widely used as an anti-aging, anti-stress dietary supplement. Despite these well-documented activities in animal models, DHEA supplementation in humans has yielded inconclusive results and the value of DHEA replacement in humans is controversial. Such widely different outcomes in rodents and humans have been referred to as ‘the DHEA conundrum’. Moreover, the potential therapeutic use of DHEA is limited by its side effects due to its conversion to sex hormones.


One possibility to explain these discrepancies is that a metabolite(s) of DHEA, rather than DHEA itself, may be necessary for its full action in human physiology. DHEA undergoes extensive conversion and derivatization to multiple products by phase 1 reactions involving the cytochrome P450 system, and studies have shown that these phase 1 products can be more potent than parental DHEA. Phase 1 reactions frequently decline in elderly subjects, and since such subjects have been the major participants in human DHEA treatment studies, it is possible that biologically active metabolites of DHEA were not produced in adequate amounts in previous human studies. It is also possible that qualitative changes in DHEA metabolism between rodents and humans will account for these differences.


DHEA oxidation via the action of the enzyme CYP7B leads to the 7-hydroxy derivatives of C-19 steroids, which are collectively present in low nanomolar concentrations in human circulation and are not readily metabolized to potent androgens or estrogens. Many of the functions initially attributed to DHEA from observations in rodents are now thought to be properties of these oxygenated metabolites, particularly AET.

 

Molecular Structure of Androstenetriol


AET possesses some of the anti-inflammatory and GC-opposing activities that have been attributed to DHEA, but with greater apparent potency. Studies with AET demonstrate it markedly up regulates host immune response, prevents immune suppression, modulates inflammation and improves survival after lethal infections by pathogens and lethal radiation. (1, 3, 5, 6)


AET has been shown to be protective against traumatic shock. Traumatic shock activates the hypothalamic-pituitary-adrenal axis (HPA) to mediate a cascade of defensive mechanisms that often include overwhelming inflammatory response and immunosuppression, which may lead to multiple organ failure. In a relevant traumatic hemorrhagic shock rodent model that applies to both combat and civilian sectors, AET provided a significant protective effect and improved survival. In a murine thermal injury model that includes glucocorticoid-induced osteopenia, AET significantly preserved bone mineral content, restored whole body bone mineral content and bone growth, suggesting reversal of GC-mediated adverse effects.


Since AET is a naturally occurring compound there is no patent protection leaving the door wide open for AET analogue research. Harbor BioSciences, Inc. – http://www.harborbiosciences.com/ (Public, OTC:HRBR – http://www.google.com/finance?q=OTC:HRBR ) is exploring a synthetic derivative of AET for the treatment of diseases with underlying chronic inflammation. HRBR has developed 17alpha-Ethynyl-5-androsten-3beta, 7beta, 17beta-triol (HE3286), a synthetic derivative AET. (1, 2, 4, 7)


Within the past two years, animal model studies of HE3286 successfully demonstrate the treatment of lung inflammation without immune suppression, the reduction of established disease of rheumatoid arthritis, and both glucose-lowering and cholesterol-lowering effects. Harbor BioSciences most ambitious project to date is their recently released data regarding that plasma levels of AET positively correlate with BMI in healthy men and women.(1) These observations suggest a compensatory role for AET in preventing the development of metabolic syndrome and obesity. The AET structural core may provide the basis for novel pharmaceuticals to treat this disease, HE3286. Stay tuned.



1. Auci DL, Ahlem CN, Kennedy MR, Page TM, Reading CL, Frincke JM. A Potential Role for 5-Androstene-3[beta],7[beta],17[beta]-triol in Obesity and Metabolic Syndrome. Obesity. http://www.nature.com/oby/journal/vaop/ncurrent/abs/oby2010204a.html


2. Conrad D, Wang A, Pieters R, et al. HE3286, an oral synthetic steroid, treats lung inflammation in mice without immune suppression. Journal of Inflammation 2010;7(1):52. http://www.journal-inflammation.com/content/7/1/52


3. Loria RM. Antiglucocorticoid function of androstenetriol. Psychoneuroendocrinology 1997;22 Suppl 1:S103-8.


4. Lu M, Patsouris D, Li P, et al. A new antidiabetic compound attenuates inflammation and insulin resistance in Zucker diabetic fatty rats. American Journal of Physiology – Endocrinology And Metabolism 2010;298(5):E1036-E48. http://ajpendo.physiology.org/content/298/5/E1036.full


5. Malik AK, Khaldoyanidi S, Auci DL, et al. 5-androstene-3?,7?,17?-triol (?-AET) Slows Thermal Injury Induced Osteopenia in Mice: Relation to Aging and Osteoporosis. PLoS ONE;5(10):e13566. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0013566


6. Marcu AC, Paccione KE, Barbee RW, et al. Androstenetriol Immunomodulation Improves Survival in a Severe Trauma Hemorrhage Shock Model. The Journal of Trauma 2007;63(3):662-9.


7. Offner H, Firestein GS, Boyle DL, et al. An Orally Bioavailable Synthetic Analog of an Active Dehydroepiandrosterone Metabolite Reduces Established Disease in Rodent Models of Rheumatoid Arthritis. Journal of Pharmacology and Experimental Therapeutics 2009;329(3):1100-9. http://jpet.aspetjournals.org/content/329/3/1100.full


8. Stiles AR, McDonald JG, Bauman DR, Russell DW. CYP7B1: One Cytochrome P450, Two Human Genetic Diseases, and Multiple Physiological Functions. Journal of Biological Chemistry 2009;284(42):28485-9.

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Methylstenbolone

Diagram of molecule

Chemical Name(s):
2,17a-Dimethyl-17b-hydroxy-5a-androst-1-en-3-one
Chemical Formula: C21H32O2
Molecular Weight: 316.5
CAS: NA
Q Qatio: 3.9
Anabolic #: 660
Androgenic #: 170
Oral Bioavailability: Estimated at 50%
AR Binding Affinity: NA
SHBG Binding Affinity: NA
Half Life: NA
Legal Status (US): Not listed as a controlled substance
Average Dose:
5-20mg/day standalone
1-5mg/day when stacked
Average Cycle Length: 2-4 weeks

 

Stimulator
Inhibitor

 

 
-5
-4
-3
-2
-1

0
1
2
3
4
5

Muscle Gain

[][][][][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Strength Gain

[][][][][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Fat Gain (negative indicates fat loss)

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Water Retention (extra-cellular bloat)

[][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Aggression

[][][][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Libido

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Acne

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Hair Loss

[][][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Prostate Enlargement

[][][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Liver Toxicity

[][][][][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Lethargy

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

 

Characteristics

Although this compound cannot convert to estrogen, it will bind strongly to SHBG, thus increasing freely circulating estrogen (and testosterone). While there is a lack of anecdotal feedback from this compound to tell the real world effect this compound may have on causing gyno, experience with related compounds tell us gyno symptoms may occur.

Users should be very careful with methylstenbolone and start out with a very low dose. This compound will likely produce a rapid increase in intracellular water retention by inhibiting 11-beta hydroxylase and building up levels of mineralcorticoids that will encourage sodium and water retention.

Gains upwards of 20-25lbs in 4 weeks are probably possible with this compound. However the liver toxicity issues would likely be the first reason why someone wouldn’t be able to make incredible gains from this compound. For this reason it would be extremely important to pre-condition the liver with a liver protecting supplement prior to cycling this compound, while continuing use throughout the cycle and during PCT.

The strength increases from this compound will likely encourage weight lifting heavier than tendons and joints are prepared to lift. It is recommended to be cautious of this and to naturally build up strength levels prior to cycling this steroid.

Using a low dose of methylstenbolone with a moderate dose of a non-methylated compound would be an acceptable way to try to limit the side-effects from this compound, although caution would still need to be taken for liver health no matter what dose is used.

Because of the strength and weight gain this compound would offer it would likely be best used as part of a bulking cycle.

Availability: 

UltraDrol by Antaeus Labs

Related Discussion

The Official Methylstenbolone Thread
Posted by Eric

References

Anabolic Pharmacology
Seth Roberts (2009)

Cynostane

Diagram of molecule

Chemical Name(s):

2-cyano-17a-methyl-17b-hydroxy-androstan-3-one
2-cyano-17a-methyl-17b-hydroxy-androst-3-one (incorrect name)
Chemical Formula: C21H31NO2
Molecular Weight: 329
CAS: NA
Q Qatio: NA
Anabolic #: NA
Androgenic #: NA
Oral Bioavailability: Estimated at 40%
AR Binding Affinity: NA
SHBG Binding Affinity: NA
Half Life: NA
Legal Status (US): Not listed as a controlled substance
Average Dose:
40-50mg/day standalone
20-30mg/day when stacking
Average Cycle Length: 4-6 weeks
Stimulator
Inhibitor

-5
-4
-3
-2
-1

0
1
2
3
4
5

Muscle Gain

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Strength Gain

[][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Fat Gain (negative indicates fat loss)

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Water Retention (extra-cellular bloat)

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Aggression

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Libido

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Acne

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Hair Loss

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Prostate Enlargement

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Liver Toxicity

[][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Lethargy

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Characteristics

2-cyano-dromostolone is a 17aa molecule relatively new to the scene with very few reviews as of yet.

It has a cyano group attached to the 2 position. The chemical structure is the same as methyldrostanolone (Superdrol), except it has a CN group on the 2 position instead of a methyl group. It is a C-17aa steroid and it will be liver toxic. Although, due to the lack of the 4-ene on ring A and lack of 2-methylation, liver toxicity may be reduced relative to a di-methylated steroid such as Superdrol.

So far, feedback is very limited for this compound. However results would be expected to be fairly lean as this compound cannot convert to estrogen. Based on the chemical structure the anabolic potency would appear to be fairly potent with moderate androgenic potency.

At the time of this writing there was only one manufacturer to bring this product to the market and there seems to have been a nomenclature mistake on the labeling for this steroid. The chemical name contains the term “androst”, assuming that there is some sort of ene group on ring A. But there does not seem to be such mention of an ene group on ring A. Therefore, the term androst should be androstan. But if this is the case, the 2-cyano group needs to be stated as alpha or beta. This makes a big difference, since usually C2-alpha groups are significantly more effective than beta.

There are studies about other 2-cyano steroids such as 2-cyano-DHT and 2-cyano-progesterone. In separate studies, one done on dogs, it was seen that both of these 2-cyano steroids caused inhibition of 3b-HSD enzyme. This inhibition would cause severe adrenal suppression. This is a very unsafe inhibition. Whether it occurs in this cyano steroid is unknown, but users need to be aware of this possibility.

Common Clones:

Cynostane by Anabolic Innovation


Related Discussion

The Official Cynostane Thread
Posted by Eric

References

Anabolic Pharmacology
Seth Roberts (2009)

Dimethazine

Diagram of molecule

Chemical Name(s):
17beta-hydroxy 2alpha,17alpha-dimethyl 5alpha-androstan 3-one azine
Chemical Formula: C42H68N2O2
Molecular Weight: 632
CAS: NA
Q Qatio: 2.2
Anabolic #: 210
Androgenic #: 95
Oral Bioavailability: Estimated at 40%
AR Binding Affinity: NA
SHBG Binding Affinity: NA
Half Life: NA
Legal Status (US): Not listed as a controlled substance
Average Dose:
20-40mg/day standalone
10-20mg/day when stacked
Average Cycle Length: 2-4 weeks
Stimulator
Inhibitor

-5
-4
-3
-2
-1

0
1
2
3
4
5

Muscle Gain

[][][][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Strength Gain

[][][][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Fat Gain (negative indicates fat loss)

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Water Retention (extra-cellular bloat)

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Aggression

[][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Libido

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Acne

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Hair Loss

[][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Prostate Enlargement

[][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Liver Toxicity

[][][][][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Lethargy

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Characteristics

Dimethazine is actually two steroid molecules bound together by a nitrogen atom. Upon ingestion, stomach acid separates the two steroid molecules that closely resemble methyldrostanolone (Superdrol).

Although dimethazine appears very similar to methyldrostanolone, the presence of a nitrogen at the 3rd position appears to increase its androgenic potency relative to its anabolic potency (210/95 compared to 400/20 for methyldrostanolone). Therefore, dimethazine could be considered a slightly weaker form of methyldrostanolone, but perhaps less likely to cause gyno related issues because of its higher relative androgenic value (and ability to antagonize estrogenic effects).

Otherwise, all side-effects and benefits could be considered relatively the same as methyldrostanolone. Liver toxicity and its associated side-effects of general sickness should still be expected, especially if the liver becomes compromised. Using a liver protecting supplement prior to and during a cycle of Dimethazine would be very important.

The quick gains in size and strength will likely be accompanied by increases in intense back pumps, high blood pressure, shortness of breath and oily skin. Vascularity would also be expected to improve with this compound due to the increase in extra-cellar water and possible decrease in subcutaneous water weight.

Because this compound is a 17aa oral, it is not recommended to be stacked with other 17aa oral steroids.

Common Clones:

Dymethazine by IForce


Related Discussion

The Official Dimethazine Thread
Posted by Eric

References

“Oral administration of an anabolic-androgenic steroid dimethazine increases the growth and food conversion efficiency and brings changes in molecular growth responses of carp (Cyprinus carpio) tissues”

LONE K. P. (1) ; MATTY A. J. ;
Nutrition reports international

“Contribution to the study of the proteoanabolic effects of dimethazine. (Clinical research)”
CEI C, ANSELMI G.
Gazz Med Ital. 1963 Feb;122:57-61

“A new steroid having proteo-anabolic action: dimethazine.”
DE RUGGIERI P, MATSCHER R, GANDOLFI C, CHIARAMONTI D, LUPO C, PIETRA E, CAVALLI R.Arch Sci Biol (Bologna). 1963 Jan-Mar;47:1-19.

Dienedione (Tren)

Diagram of molecule

Chemical Name(s):

19-norandrosta-4,9-diene-3b,17b-dione
estra-4,9-diene-3b,17b-dione
4,9 Estra
Chemical Formula: C18H22O2
Molecular Weight: 270
CAS: NA
Q Qatio: NA
Anabolic #: NA
Androgenic #: NA
Oral Bioavailability: Estimated at 20%
AR Binding Affinity: 5
SHBG Binding Affinity: NA
Half Life: NA
Legal Status (US): Listed as a controlled substance
Average Dose:
100-200mg/day standalone
50-100mg/day when stacking
Average Cycle Length: 4-6 weeks
Stimulator
Inhibitor

-5
-4
-3
-2
-1

0
1
2
3
4
5

Muscle Gain

[][][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Strength Gain

[][][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Fat Gain (negative indicates fat loss)

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Water Retention (extra-cellular bloat)

[][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Aggression

[][][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Libido

[][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Acne

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Hair Loss

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Prostate Enlargement

[][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Liver Toxicity

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Lethargy

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Characteristics

Dienedione is a non-methylated steroid that converts to a steroid known as 17b-hydroxy-estra-4,9,(10)-dien-3-one (dienolone).

Although dienedione may have some anabolic activity on its own, it gets most of its effects from conversion to dienedrone by interaction with 17b-HSD. This steroids overall effects are somewhere between trenbolone and nandrolone.

Dienedione is known for causing night sweats via its powerful thermogenic effects similar to trenbolone. This thermogenic effect makes dienedione an excellent choice for dropping bodyfat during cutting cycles.

As a 19-nor this compound has decent progestational effects which may lead to gyno symptoms, libido loss and aggressive mood swings. Part of the reason gyno may be a problem with this compound is also because it lacks androgenic potency and down-regulates DHT levels during cycle, which is the body’s natural estrogen blocker.

Dienedione does not convert to estrogen, although it can still lead to the side-effects mentioned above. Because this compound is not 17aa liver toxicity is not really a concern. However some users have reported elevated liver enzyme values during cycle, although this could be related to other factors.

Users usually experience rapid gains in strength and aggression, followed by significant weight gain after several weeks. The results are generally fairly lean with only minor bloat due to the progestational effects.

Dienedione can be used as a standalone. In an effort to prevent libido loss and gyno, it may be stacked with testosterone or one of its non-aromatizing metabolites to help keep DHT levels elevated during cycle.

Common Clones:

Dienedrone by Advanced Muscle Science (AMS)
Liquidrone UTT by Advanced Muscle Science (AMS)
X-Tren by Competitive Edge Labs (CEL)
Tren Xtreme by American Cellular Labs
Tren 250 by Genetic Edge Technologies (GET)
Trena by Nutracoastal


Related Discussion

The Official Dienedione (Tren) Thread
Posted by Eric

References

Anabolic Pharmacology
Seth Roberts (2009)

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