Glycyrrhetinic acid (a topical fat loss ingredient)

[Nightwanderer]

So as I understand it, once this chemical is broken down into metabolites by the body, one of those metabolites helps keep
cortisol active, and encourages kidney build up? Can someone
help me understand why this is something a consumer would want in a cutting product?

Glycyrrhetinic acid - Wikipedia, the free encyclopedia

The structure of glycyrrhetinic acid is similar to that of cortisone. Both molecules are flat and similar at position 3 and 11. This might be the basis for licorice's anti-inflammatory action.

3-Beta-D-(monoglucuronyl)18-beta-glycyrrhetinic acid, a metabolite of glycyrrhetinic acid inhibits the conversion of active cortisol to inactive cortisone in the kidneys. This occurs via inhibition of the enzyme by inhibiting the enzyme 11-beta-hydroxysteroid dehydrogenase. As a result, cortisol levels are high within the collecting duct of the kidney. Cortisol has intrinsic mineralocorticoid properties (that is, it acts like aldosterone and increases sodium reabsorption) that work on ENaC channels in the collecting duct. Hypertension develops due to this mechanism of sodium retention. People often have high blood pressure with a low renin and low aldosterone blood level. The increased amounts of cortisol binds to the unprotected, unspecific mineralocorticoid receptors and induce sodium and fluid retention, hypokalaemia, high blood pressure and inhibition of the renin-angiotensin-aldosterone system. Therefore licorice should not be given to patients with a known history of hypertension.

 

[thesinner]

I believe it works in topicals because they are not systematic, thus only inihibiting the conversion of cortisone to cortisol locally.

 

[Nightwanderer]

I believe it works in topicals because they are not systematic, thus only inihibiting the conversion of cortisone to cortisol locally.

but the article is quoted as saying it's the other way around, that it prevents the kidneys from deactivating cortisol through metabolism, So, unless the article got things mixed up, it would seem this chemical is actually a bad thing. Either that or it's a flaw of my understanding, is cortisol only undesirable when inactive?

 

[Sir Savage]

I believe there is a difference between kidney tissue and adipose tissue.

And there is a difference between systemic and local application.

 

[Nightwanderer]

I believe there is a difference between kidney tissue and adipose tissue.

And there is a difference between systemic and local application.

yes, but I wouldn't assume that just because you administer a chemical transdermally in a localized area that it would only affect certain tissues in certain areas. Otherwise, you wouldn't be able to drop say, liquid LSD for example under your tongue, in your eye, or in larger doses on the skin and not have it affect your brain. Venomous frogs that are lethal to the touch might be another good example of this. Besides, regardless of the limitations of topical mediums, it still doesn't give me any clue as to what benefits this ingredient would provide. In short, I'm merely asking 'what is its purpose in fat reduction, and how does it work?'
'

 

[Rodja]

yes, but I wouldn't assume that just because you administer a chemical transdermally in a localized area that it would only affect certain tissues in certain areas. Otherwise, you wouldn't be able to drop say, liquid LSD for example under your tongue, in your eye, or in larger doses on the skin and not have it affect your brain. Venomous frogs that are lethal to the touch might be another good example of this. Besides, regardless of the limitations of topical mediums, it still doesn't give me any clue as to what benefits this ingredient would provide. In short, I'm merely asking 'what is its purpose in fat reduction, and how does it work?'
'

Again, you are referring to systemic instead of localized. With GA locally applied in the carrier within Napalm, the majority of the actives stays in the applied area, thus reducing cortisol deposits.
FYI, localized carriers (e.g. the active in Napalm, Lipo-U) are used to apply supplements in a localized area. This metjod not only makes spot reduction possible, but also severely reduces the systemic effects of Y-HCl, etc. This is why adding clen to the carrier will not have the negative effects on VO2, BP, etc.

 

[Colin]

but the article is quoted as saying it's the other way around, that it prevents the kidneys from deactivating cortisol through metabolism, So, unless the article got things mixed up, it would seem this chemical is actually a bad thing. Either that or it's a flaw of my understanding, is cortisol only undesirable when inactive?

GA lowers cortisol.

The text below,taken from the Napalm writeup,explains in detail how GA acts as a fat loss agent.


Glycyrrhetinic acid
Licorice has a lengthy historical association with reduction fat mass and weight loss dating back to the 4th century BC. The Greek physician Theophrastus noted that licorice root granted his patience 'freedom from hunger and thirst'(24), an observation that was reaffirmed in the 1st century BC by Plinius (25). It wasn't until modern technological advancements allowed us to characterize the licorice root in order to reveal the main active ingredient: glycyrrhetinic acid (GA).

These ancient observations are supported thoroughly by modern literature which documents the relationship between GA and 11?-hydroxysteroid dehydrogenase (11HSD) (26). For our purposes we will concern ourselves with the first of two 11HSD subtypes. 11HSD1 is found in subcutaneous adipocytes in a relatively lesser abundance than it's visceral counterpart (27). However, 11HSB-1 is sufficiently concentrated to perform its primary function and influence the level of cortisol by reactivating the inactive cortisone. A hyperactive mutant form of 11HSD-1 is observed in cases of the pathologically obese, suggesting that inhibition of this enzyme will facilitate reduction in adipocytic mass.

This is where GA performs its duties and helps you get skinny, the ultimate result can be attributed to a few proximate causes. Firstly, the vital role of GA and cortisol. By reducing the local availability of cortisol via 11HSD-1 inhibition (28), GA causes a reduction in the concentration of intracellular triglycerides (29), in addition to impeding the differentiation preadipocytes(30).

The merits for topical applications of GA are not limited to the above, but further investigation also showed the ability for GA to positively affect fat metabolism by inactivating fat lipase and increasing mobilization of adipose stores (31).


Here is the full write up,with all scientific referances noted and available via Pubmed.com

http://www.avantresearch.com/products/napalm/research

 

[thebigt]

my question concerns the molecular weight of formestane, and if 1 or 2 grams could be added to napalm. if the answer is no, what is a localized carrier that would work. imo formestane would be a great spot reducer to add to a local carrier, particularly one as effective as napalm.

 

[thesinner]

my question concerns the molecular weight of formestane, and if 1 or 2 grams could be added to napalm. if the answer is no, what is a localized carrier that would work. imo formestane would be a great spot reducer to add to a local carrier, particularly one as effective as napalm.

It's not going to work so well in a hydrophillic carrier. You would want a carrier more akin to Abliterate.

 

[thebigt]

It's not going to work so well in a hydrophillic carrier. You would want a carrier more akin to Abliterate.

never got to try it before it was dc'd. got any ideas for a local carrier, that would be good for formestane. to bad the napalm wouldn't work.

 

[Rodja]

Lipo-U is an ampiphilic carrier.

 

[thebigt]

Lipo-U is an ampiphilic carrier.

thanks, how many grams of form could i add? ive heard it's almost saturated. also how much trouble will it be to get the form mixed in the lipo? again, thanks. been looking for localized carrier for form.

 

[Rodja]

thanks, how many grams of form could i add? ive heard it's almost saturated. also how much trouble will it be to get the form mixed in the lipo? again, thanks. been looking for localized carrier for form.

Not too much, maybe 2 grams, but I am not sure how soluble formestane is, so it might be a pain in the ass to mix.

 

[dsade]

Form is a pain in the ass to mix. I would not attempt more than a gram into the already close to saturated Lipo-Ultra.

 

[thebigt]

Form is a pain in the ass to mix. I would not attempt more than a gram into the already close to saturated Lipo-Ultra.

would adding just 1 gram of form even make enough difference to mess with?

 

[dsade]

would adding just 1 gram of form even make enough difference to mess with?

Being localized, I would say yes.

 

[thebigt]

Being localized, I would say yes.

ok, it's worth a try, i stocked up and have about 42 grams of form left.

 

[Bobaslaw]

but the article is quoted as saying it's the other way around, that it prevents the kidneys from deactivating cortisol through metabolism, So, unless the article got things mixed up, it would seem this chemical is actually a bad thing. Either that or it's a flaw of my understanding, is cortisol only undesirable when inactive?

You need to keep in mind that 11BetaHSD-1 is a bidirectional enzyme and is expressed as 2 isoforms. 11BetaHSD-1 reductase is responsible for activating cortisone into cortisol. 11BetaHSD-1 dehydrogenase is responsible for the opposite and inactivates cortisol into cortisone.
So, if a compound is not selective and inhibits all 11BetaHSD-1, then it can cause certain local tissues to be unable to deactivate cortisol properly.
An example is the testes. Leydig cell 11BetaHSD-1 is predominatly the dehydrogenase (oxidative) not the reductase we are commonly referencing. Inhibiting BetaHSD-1 in this tissue actually raises cortisol in the Leydig cells, thus inhibiting their response to LH, leading to decrease in Testosterone production. (Many Studies on this).

 

[Bobaslaw]

Again, you are referring to systemic instead of localized. With GA locally applied in the carrier within Napalm, the majority of the actives stays in the applied area, thus reducing cortisol deposits.
FYI, localized carriers (e.g. the active in Napalm, Lipo-U) are used to apply supplements in a localized area. This metjod not only makes spot reduction possible, but also severely reduces the systemic effects of Y-HCl, etc. This is why adding clen to the carrier will not have the negative effects on VO2, BP, etc.

I have always questioned the concept of transdermals keeping the active "local" and not going systemic.
I have thought to myself how is this possible if many transdermal applications are ment for systemic delivery.
(Trandermal Steroids, Nicotine Patch, Birth Control Patch,etc)

Based on what you are saying it seems that the type of transdermal carrier is responsible for local vs systemic action in a transdermal application? Can you please explain this further?

My concern was always the possibility of GA going systemic and affectintg the testes and 17B-HSD.

 

[Sir Savage]

Par Deus explains this in his write up, which can be found in the Napalm write up above.

 

[Bobaslaw]

Par Deus explains this in his write up, which can be found in the Napalm write up above.

Napalm Research | Avant Research

The writeup does not answer my question. It only states how the transdermal makes it past the dermal layers to the adipose tissue. It says nothing about how the carrier is able to keep the active from being absorbed into blood vessels in its journey to the adipose tissue.

My question is:

By what means does a specific TD carrier in this product avoid the posibility of the compound becoming systemic as with most transdermal or sub-q drug applications?

Take Care.

 

[Sir Savage]

Again, the answer can be found in the Napalm write up. Par Deus wrote an article on this very thing many years ago, the link to which is in the Napalm write up.

Here it is-

http://www.mindandmuscle.net/articles/CalebStone/topicalfatloss?page=0,1

It starts on page 2.

If you're looking for specifics on the carrier itself, we don't divulge some of that because other companies would readily copy it.

 

[Bobaslaw]

Again, the answer can be found in the Napalm write up. Par Deus wrote an article on this very thing many years ago, the link to which is in the Napalm write up.

Here it is-

http://www.mindandmuscle.net/articles/CalebStone/topicalfatloss?page=0,1

It starts on page 2.

If you're looking for specifics on the carrier itself, we don't divulge some of that because other companies would readily copy it.

Thanks, this is probably the article you meant when you previously refereneced me to "the Napalm writeup above" .
The only writeup "above" was in post#7 in which I did not find the info, which made things confusing... Thus my repeated question.

Thanks again for this updated link.

 

[Sir Savage]

Yeah, there's actually a link to that article in the Napalm write up. It might be hard to spot, though.

 

[Bobaslaw]

Yeah, there's actually a link to that article in the Napalm write up. It might be hard to spot, though.

I have a question about the specifics of the article excerpt:

What we also need is for a minimal amount of the drug to be delivered systemically, and once again, the "special delivery solvent" was shown to be superior. Maximal blood levels of all three compounds occurred at the 2 hour mark. W displayed levels about 1/3 that of O and 1/2 that of WO.

So from the writeup it seems the transdermal carrier in the Avant products ONLY reduces systemic delivery to 1/3rd that of oral delivery, mg for mg of active, I assume.
I am trying to use this information to figure out how much GA is actually going systemic (in Napalm) compared to oral GA. If I knew how much GA is in Napalm, I could compare and see what oral dosage that would be eqivelent to.
How much GA is in a serving of Napalm?

 

[DevilSmack]

Did all the Formestane fall off of the face of the earth? I can't find it anywhere.

I have some Liposolve that I have used yet and I wanted to try some Formestane with it topically on my chest.

 

[thebigt]

Did all the Formestane fall off of the face of the earth? I can't find it anywhere.

I have some Liposolve that I have used yet and I wanted to try some Formestane with it topically on my chest.

you talking about the liposolve sold by giant? is it local or systematic?

 

[DevilSmack]

^ yes and it's local. A local anti-E to gyno tissue might be of some help.

 

[Bobaslaw]

Yeah, there's actually a link to that article in the Napalm write up. It might be hard to spot, though.

I have a question about the specifics of the article excerpt:

What we also need is for a minimal amount of the drug to be delivered systemically, and once again, the "special delivery solvent" was shown to be superior. Maximal blood levels of all three compounds occurred at the 2 hour mark. W displayed levels about 1/3 that of O and 1/2 that of WO.

So from the writeup it seems the transdermal carrier in the Avant products ONLY reduces systemic delivery to 1/3rd that of oral delivery, mg for mg of active, I assume.
I am trying to use this information to figure out how much GA is actually going systemic (in Napalm) compared to oral GA. If I knew how much GA is in Napalm, I could compare and see what oral dosage that would be eqivelent to.
How much GA is in a serving of Napalm?

Can someone from Avant comment on the info above from the Napalm Writeup. Because to me it seems that the claims of the transdermal carrier having only localized action is not completely true, as the writeup shows that systemic blood levels of actives did go up, but only 1/3 that of an oral dose.
This makes me pose additional questions regarding how much GA is in Napalm. I want to actually figure out how much of this active I am getting systemicly so I can draw my own conclusions from actual study information rather than just hearing "No systemic action here, only local". The reason I am so adament is because of my test levels while naplam (not completely sure, since other factors may have contributed as well).
Please let me know if I have mis-interpreted anything from the writeup regarding your product.

Thank You.

 

[Sir Savage]

Yes, you are correct. Peak blood concentrations of whatever you are delivering would occur two hours after administration, and the research suggests that our carriers would have a max peak of 1/3 that of oral.

Sure, some of the actives go systemic. That can't be completely avoided and we've never claimed that. But it's only 1/3 of that of oral, which is a very significant difference. Think of it this way- 100% vs. 33.33%. That is an enormouse difference, hence the terms systematic vs. local.

Now, in the following study on GA in a topical solution-

1: Steroids. 2005 Jul;70(8):538-42. Epub 2005 Apr 12. Links
Glycyrrhetinic acid, the active principle of licorice, can reduce the thickness of subcutaneous thigh fat through topical application.Armanini D, Nacamulli D, Francini-Pesenti F, Battagin G, Ragazzi E, Fiore C.
Department of Medical and Surgical Sciences-Endocrinology, University of Padua, Via Ospedale 105, 35100 Padua, Italy. [email protected]

Cortisol is involved in the distribution and deposition of fat, and its action is regulated by the activity of 11beta-hydroxysteroid dehydrogenase. Glycyrrhetinic acid, the active principle of licorice root, blocks 11beta-hydroxysteroid dehydrogenase type 1, thus reducing the availability of cortisol at the level of adipocytes. We evaluated the effect of topical application of a cream containing glycyrrhetinic acid in the thickness of fat at the level of the thigh. Eighteen healthy women (age range 20-33 years) with normal BMI were randomly allocated to treatment, at the level of the dominant thigh, with a cream containing 2.5% glycyrrhetinic acid (n=9) or with a placebo cream containing the excipients alone (n=9). Before and after 1 month of treatment both the circumference and the thickness of the superficial fat layer of the thighs (by ultrasound analysis) were measured. The circumference and the thickness of the superficial fat layer were significantly reduced in comparison to the controlateral untreated thigh and to control subjects treated with the placebo cream. No changes were observed in blood pressure, plasma renin activity, plasma aldosterone or cortisol. The effect of glycyrrhetinic acid on the thickness of subcutaneous fat was likely related to a block of 11beta-hydroxysteroid dehydrogenase type 1 at the level of fat cells; therefore, glycyrrhetinic acid could be effectively used in the reduction of unwanted local fat accumulation.

PMID: 15894038 [PubMed - indexed for MEDLINE]

you'll notice that no changes were found in blood pressure, plasma renin activity, plasma aldosterone or cortisol, all of which indicate that very little of the GA went systemic, since GA (or licorice in general) is well known to exert these effects when taken systemically.

And when you add in the fact that I don't think the authors of the study used many of the ingredients in our carrier, the concern over GA (or any other ingredient) going systemic in significant amounts really seems to become a non-issue.

 

[Bobaslaw]

Yes, you are correct. Peak blood concentrations of whatever you are delivering would occur two hours after administration, and the research suggests that our carriers would have a max peak of 1/3 that of oral.

Sure, some of the actives go systemic. That can't be completely avoided and we've never claimed that. But it's only 1/3 of that of oral, which is a very significant difference. Think of it this way- 100% vs. 33.33%. That is an enormouse difference, hence the terms systematic vs. local.

Now, in the following study on GA in a topical solution-



you'll notice that no changes were found in blood pressure, plasma renin activity, plasma aldosterone or cortisol, all of which indicate that very little of the GA went systemic, since GA (or licorice in general) is well known to exert these effects when taken systemically.

And when you add in the fact that I don't think the authors of the study used many of the ingredients in our carrier, the concern over GA (or any other ingredient) going systemic in significant amounts really seems to become a non-issue.

Thanks for the info

Can you indulge me a bit more and let me know how much GA is in a serving of Napalm? It's one question that no one here has answered and I have not found this answer in my searches so far.

 

[Sir Savage]

Don't think we're quite ready to release that yet, my man. Apologies.

 

[Bobaslaw]

Don't think we're quite ready to release that yet, my man. Apologies.

Really!?! Thats a bit strange since it's only a dosage amount.
Unfortunately then, it does not enable me to determine how much of the GA is actually going systemic and see whether it is anywhere near a significant enough dose.
Yes, I know you keep telling me about the insignificant amount and all, but in this game, I have come to realize I can only trust what I know for a fact from studies and plain math.
Unfortunately, in your previous post on the Topical GA study, it does not take have Test levels as a parameter. I can not just "assume" there is no change, just because other hormone levels seem unaltered. That is just not a scientific way to detemin such things.
So, If you cannot say how much GA is in Napalm, nor show any studies/trials that show what test levels are before and after Napalm use, I have to assume (unfortunately)the possibility that enough GA is making it systemically to affect testicular steroidogenesis.
This is truly unfortuante, as knowing the GA dosage could also clear this up.

Take Care.

 

[Sir Savage]

Well, the problem from our perspective is that if we release information on specifics of our formula, it's going to accelerate the copy cats.

In the past, we've been copied repeatedly. SesaThin, Lipoderm-Ultra, etc. Hell, this very board was started as a place to discuss the copying of our old androgen products. There are essentially no intellectual property rights in the supplement industry, so we have to do what we can to protect our products from copycats. Sometimes, that means developing proprietary formulas.

However, a few notes about your concerns-

1) You CAN use plasma cortisol levels and the other criteria measured in the study as a proxy for systemic distribution and ultimately, the impact on testosterone levels. The reason is that if it's not getting into other areas of the body in any significant amount, then there's no reason to think it would accumulate in the hypothalamus, pituitary, or testes and impact testosterone. It's not perfect, no, but science doesn't promise us perfection- only evidence.

In your case, say you calculated the amount of GA that goes systemic. Then what? Is that strong evidence that it reduced your testosterone? Of course not. It's not a controlled experiment with a large enough sample size to determine anything.

2) There is some evidence that licorice can cause a reduction in testosterone, but there's no direct evidence that's GA that causes it. There are many other compounds in licorice that could be responsible.

 

[Bobaslaw]

Well, the problem from our perspective is that if we release information on specifics of our formula, it's going to accelerate the copy cats.

In the past, we've been copied repeatedly. SesaThin, Lipoderm-Ultra, etc. Hell, this very board was started as a place to discuss the copying of our old androgen products. There are essentially no intellectual property rights in the supplement industry, so we have to do what we can to protect our products from copycats. Sometimes, that means developing proprietary formulas.

However, a few notes about your concerns-

1) You CAN use plasma cortisol levels and the other criteria measured in the study as a proxy for systemic distribution and ultimately, the impact on testosterone levels. The reason is that if it's not getting into other areas of the body in any significant amount, then there's no reason to think it would accumulate in the hypothalamus, pituitary, or testes and impact testosterone. It's not perfect, no, but science doesn't promise us perfection- only evidence.

In your case, say you calculated the amount of GA that goes systemic. Then what? Is that strong evidence that it reduced your testosterone? Of course not. It's not a controlled experiment with a large enough sample size to determine anything.

I can use the amount to figure out the equivelent oral dosage and compare with studies on GA/decresed testosterone where the oral dosages used are presented. I would have to take into account that oral doses would partially be taken up in the liver(targeting given HSD enzymes there) before the rest making it systemic, as opposed to the transdermal route which would have a higher percentage of the given dose making it to target tissues systemically (since the liver would not take it up first).
Still, it is something to work off of... Not perfect in the least.
A test study for transdermal doses using your transporter would be the best concrete documentation, however.

2) There is some evidence that licorice can cause a reduction in testosterone, but there's no direct evidence that's GA that causes it. There are many other compounds in licorice that could be responsible.

There numerous studies on GA itself and its effects on leydig cell function and steroidogenesis.


Thanks for the info and PM. I appreciate it

 

[Sir Savage]

Link?

There's new research out that shows administration of GA + corticosterone reduced testosterone in rats, but not GA alone that I'm aware of.

 

[Bobaslaw]

Link?

There's new research out that shows administration of GA + corticosterone reduced testosterone in rats, but not GA alone that I'm aware of.

Yes that study (below) is pertinent and yes GA and Cort simulate the natural environment of the testes in this circumstance.
Cortisol alone does not affect steroidogenesis because Leydig Cell 11B-HSD1 dehydrogenase is able to inactivete it. 11BHSD1 dehydrogenase is predominant in the testes over the reductase. Anyhow GA alone does not affect steroidogenesis either, as in this example there is no endogenous cort being accounted for since this is an in vivo experiment. Remember, in vitro we would have a level of cort in the testes that would affect steroidogenesis if 11B-HSD1 dehydrogenase is inhibited by GA.
Thus adding Cort and GA simulates fully the in vitro eqivelent action of GA on 11B-HSD1 while in the presence of native levels of cortisol in the testes.

Inhibition of 11beta-hydroxysteroid dehydrogenase ...[J Androl. 2008 May-Jun] - PubMed Result

Inhibition of 11beta-hydroxysteroid dehydrogenase enzymatic activities by glycyrrhetinic acid in vivo supports direct glucocorticoid-mediated suppression of steroidogenesis in Leydig cells.

Hu GX, Lin H, Sottas CM, Morris DJ, Hardy MP, Ge RS.
Institute of Molecular Toxicology and Pharmacology, School of Pharmacy, 2nd Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, People's Republic of China.

Previous studies have suggested that glucocorticoid (GC) can directly affect testicular testosterone (T) biosynthesis by Leydig cells through a receptor-mediated mechanism. Interconversion of corticosterone (CORT), the active form in rodents, and 11-dehydroCORT, the biologically inert 11-keto form, is catalyzed by 11betaHSD1. This enzyme thus controls the intracellular concentration of active GC. We have postulated that elevated CORT levels resulting from stress exceed the Leydig cell's capacity for metabolic inactivation of CORT, resulting in suppressed T production. The present study tested whether inhibition of 11betaHSD1 in vivo, by the administration of glycyrrhetinic acid (GA), increases intracellular active GC concentration and thereby affects serum T concentration and Leydig cell T production. Adult Sprague-Dawley rats were treated with vehicle (corn oil), CORT, GA, or GA + CORT. Serum luteinizing hormone (LH), CORT, and T levels were measured, as were the steroidogenic capacities of purified Leydig cells. Twofold elevations of CORT were achieved by the administration of either CORT or GA alone, but in both cases there was no effect on serum T levels. However, when CORT and GA were administered in combination, serum CORT levels increased 3.5-fold (to 420 +/- 34 ng/mL) and serum T levels were reduced significantly (to 0.72 +/- 0.07 ng/mL; control, 2.12 +/- 0.23 ng/mL). Serum levels of LH were not affected by CORT, GA, or GA + CORT. Consistent with the reduced serum T levels following GA + CORT, steroidogenic enzyme expression and capacities were significantly reduced compared to control. These data support a role for 11betaHSD1 in modulating intracellular CORT concentrations and, in turn, for a direct effect of GC on Leydig cells in response to stress.

Inhibitory effect of glycyrrhetinic acid on testos...[Endocrinol Jpn. 1988] - PubMed Result

Inhibitory effect of glycyrrhetinic acid on testosterone production in rat gonads

Sakamoto K, Wakabayashi K.
Tsumura Research Institute for Pharmacology, Ibaraki, Japan.

We studied the effects of shakuyaku-kanzo-toh (a Chinese herbal medicine) and its components on testosterone production by rat gonads. We used paeoniflorin as a main component of shakuyaku (paeoniae radix), glycyrrhizin as a main component of kanzo (glycyrrhizae radix) and glycyrrhetinic acid as a main metabolite of glycyrrhizin. Oral administration of shakuyaku-kanzo-toh, glycyrrhizin, and glycyrrhetinic acid decreased in vitro basal testosterone production in Leydig cells by LH stimulation. Glycyrrhizin and glycyrrhetinic acid caused a significant decrease in testosterone production with an accumulation of 17 alpha-hydroxyprogesterone when incubated with isolated Leydig cells, while paeoniflorin showed no such effect. The inhibitory effect of glycyrrhetinic acid was far more potent than that of glycyrrhizin, causing about 90% inhibition at 10 micrograms/ml. Glycyrrhizin and glycyrrhetinic acid did not change the cyclic AMP or progesterone level in the Leydig cells. When 14C-labeled androstenedione was incubated with microsomal fraction of testicular or ovarian tissue, glycyrrhizin and glycyrrhetinic acid inhibited the conversion of androstenedione to testosterone, indicating that these compounds inhibit the activity of 17 beta-hydroxysteroid dehydrogenase (EC. 1.1.1.64). The ED50 of glycyrrhetinic acid was about 4 microM

Another reference to GA and 17B-HSD:

Identification of novel functional inhibitors of 1...[Prostate. 2005] - PubMed Result

Identification of novel functional inhibitors of 17beta-hydroxysteroid dehydrogenase type III (17beta-HSD3).

Spires TE, Fink BE, Kick EK, You D, Rizzo CA, Takenaka I, Lawrence RM, Ruan Z, Salvati ME, Vite GD, Weinmann R, Attar RM, Gottardis MM, Lorenzi MV.
Oncology Drug Discovery, Bristol-Myers Squibb, Pharmaceutical Research Institute, Princeton, NJ 08543, USA.

BACKGROUND: Endocrine therapy of prostate cancer (PCa) relies on agents which disrupt the biosynthesis of testosterone in the testis and/or by direct antagonism of active hormone on the androgen receptor (AR) in non-gonadal target tissues of hormone action such as the prostate. METHODS: In an effort to evaluate new therapies which could inhibit gonadal or non-gonadal testosterone biosynthesis, we developed high throughput biochemical and cellular screening assays to identify inhibitors of 17beta-hydroxysteroid dehydrogenase type III (17beta-HSD3), the enzyme catalyzing the conversion of androstenedione (AdT) to testosterone. RESULTS: Initial screening efforts identified a natural product, 18beta-glycyrrhetinic acid, and a novel derivative of AdT, 3-O-benzylandrosterone, as potent inhibitors of the enzyme. Further efforts led to the identification of several classes of non-steroidal, low molecular weight compounds that potently inhibited 17beta-HSD3 enzymatic activity. One of the most potent classes of 17beta-HSD3 inhibitors was a series of anthranilamide small molecules identified from a collection of compounds related to non-steroidal modulators of nuclear hormone receptors. The anthranilamide based 17beta-HSD3 inhibitors were exemplified by BMS-856, a compound displaying low nanomolar inhibition of 17beta-HSD3 enzymatic activity. In addition, this series of compounds displayed potent inhibition of 17beta-HSD3-mediated cellular conversion of AdT to testosterone and inhibited the 17beta-HSD3-mediated conversion of testosterone necessary to promote AR-dependent transcription. CONCLUSIONS: The identification of non-steroidal functional inhibitors of 17beta-HSD3 may be a useful complementary approach for the disruption of testosterone biosynthesis in the treatment of PCa. Copyright 2005 Wiley-Liss, Inc.

 

[Sir Savage]

I do not agree that GA + CORT simulate the natural environment of the testes. The only way that would make sense would be in a hyper stressed state, where CORT levels would be greatly elevated. The important thing was that GA by itself (which would mimic the natural environment of the testes in normal individuals) didn't cause a decrease in testosterone.

And this seems to pan out in the most recent research in humans-

1: Horm Res. 2006;65(2):106-10. Epub 2006 Feb 3. Links
Liquorice in moderate doses does not affect sex steroid hormones of biological importance although the effect differs between the genders.Sigurjonsdottir HA, Axelson M, Johannsson G, Manhem K, Nystrom E, Wallerstedt S.
Department of Endocrinology, Sahlgrenska University Hospital/Sahlgrenska, Göteborg, Sweden. [email protected]

BACKGROUND/AIM: Liquorice is commonly consumed, at least in the western world, and we have earlier shown that even moderate doses of liquorice have significant effects on the cortisol metabolism by inhibiting 11beta-hydroxysteroid dehydrogenase type 2. The suggestion that liquorice decreases the testosterone levels in men makes it vital to study the effect of moderate doses of liquorice on sex steroid hormones. METHODS: Fifteen women and 21 men (healthy volunteers and subjects with essential hypertension) consumed 100 g of liquorice (150 mg glycyrrhetinic acid) daily in a 9-week, open-treatment trial. Blood and 24-hour urine samples were collected for hormone analysis before and after 4 weeks of liquorice consumption and 4 weeks after cessation of liquorice intake. RESULTS: The liquorice induced a moderate decrease in the serum concentrations of dehydroepiandrostenedione sulphate in men (p = 0.002). The relative change in serum levels of dehydroepiandrosterone sulphate differed between the genders (p = 0.03). No significant changes were observed in the serum testosterone levels after 4 weeks of liquorice consumption, and the urine excretion of androgens (etiocholanolone and androstenedione) did not change. CONCLUSIONS: Liquorice in moderate doses primarily affects the cortisol metabolism and only marginally the androgen hormones. Gender may influence the action of liquorice. Copyright 2006 S. Karger AG, Basel

PMID: 16462145 [PubMed - indexed for MEDLINE]

And that's systemically. If the licorice/GA were administered locally, the effect would be expected to be roughly 1/3 of whatever reduction was seen.

 

[CryingEmo]

IMO i'd hire bobaslaw as a rep or something. *wink*