[USPlabsRep]

Is it possible to increase testosterone by lowering LH without shutting down endogenous production with exogenous sources?

[mr.cooper69]

No, LH is necessary for T production/release. The only way it'd be possible to keep producing endogenous T with low LH is if you were also administering an LH analogue or somehow managed to dramatically increase LH receptor density/sensitivity.

[thehulk0316]

31 yrs old. I don't use or have ever used AAS and has been years since I used a Ph but my LH is lower than normal but my total and free test are very high. I don't have the exact numbers but my endocrinologist implied I was on TRT or using AAS as she stated my T levels were indicative of someone supplementing. Also, she is concerned about my Lh. I was taking Vit D, magnesium, zinc, fish oils, Vit C, probiotic and a bone health complex. Since I've dropped all of them but the fish oils and added red yeast rice and coq-10 for cholesterol issues.

[USPlabsRep]

No, LH is necessary for T production/release. The only way it'd be possible to keep producing endogenous T with low LH is if you were also administering an LH analogue or somehow managed to dramatically increase LH receptor density/sensitivity.

I'm onto something

[money0351]

I'm onto something

New product?

[T-Bone]

I'm onto something

Spill the beans already.

[Bamski]

I'm onto something

Let's hear it!

[mr.cooper69]

I'm onto something

New product?

I mean, it already exists: forksolin. LH pulse won't change but the cAMP response in the testes will increase so T goes up

[USPlabsRep]

I mean, it already exists: forksolin. LH pulse won't change but the cAMP response in the testes will increase so T goes up

so far its lowering LH while increasing T with men in normal range...well its all preliminary blood that we couldn't stake a claim on but its an instant significant increase in 5 days and elevated up to 30 days. We are about to begin looking at increases in 24, 48, and 72 hours.

[MonteCedillo]

so far its lowering LH while increasing T with men in normal range...well its all preliminary blood that we couldn't stake a claim on but its an instant significant increase in 5 days and elevated up to 30 days. We are about to begin looking at increases in 24, 48, and 72 hours.

Interesting… so decreasing LH production yet getting an increase in T? Something binding with LH binding sites in the testes stimulating T release?

[xR1pp3Rx]

could effecting SGBH be causing this somehow downstream?

[kisaj]

So is it bringing test subjects from low into normal range? I never saw the point in taking something that raises total test from normal to higher normal. It would be more significant to raise free test.

[USPlabsRep]

could effecting SGBH be causing this somehow downstream?

No change in SHGB initially so free test increased and estrogen did increase but not until the midway through testing, it will need a good AI or Anti-E...

[T-Bone]

No change in SHGB initially so free test increased and estrogen did increase but not until the midway through testing, it will need a good AI or Anti-E...

Will the AI or Anti-E be included in the formula?

[USPlabsRep]

Will the AI or Anti-E be included in the formula?

working on that next plus a few cool additions..

[USPlabsRep]

cool data in yesterday

day 1 was baseline was normal on the lower side of 600
day 2 draw supplement dosed 2 hours before an increase of 80 points
day 7 draw supplement dosed 2 hours before an increase of over 200 points

there was a day three draw but the lab lost the results.

results are individual and by no means does this represent an entire population. Very promising emerging data.

[Punisher187]

Awesome news! Cannot wait til this is released!

[GoHardOrGoHme]

One way to lower LH and increase testosterone is to increase the sensitivity of LH signaling and testosterong production. So either you are upregulating a receptors on your leydig cells or you are increasing the leydig cells ability to release testosterone at a given LH level.

Another way is by causing the adrenal glands to release testosteone. By doing this you would decrease LH production because you are using an alternate route for testosterone excretion.

This is purely theoretical and I have never heard of anything being able to do either one of those proposed theories.

[USPlabsRep]

Another way is by causing the adrenal glands to release testosteone. By doing this you would decrease LH production because you are using an alternate route for testosterone excretion.

This is purely theoretical and I have never heard of anything being able to do either one of those proposed theories.

This is our theory as well currently..

[T-Bone]

Any updates on this as far as a beta release?

[mr.cooper69]

This is our theory as well currently..

In males, this pathway is usually too minor to matter.

[GoHardOrGoHme]

I have mixed feeling about this route of testosterone elevation. Allow me to elaborate in the attempt to have an analytical conversation.

A physiological increases of testosterone in healthy males does not equate to significant gains in the gym. To my knowledge, in order to truly reap the benefit of an increase of testosterone, one would have to increase levels to supraphysiological levels (this is why hormonal supplementation works so well and testboosters can't compare even if they do indeed raise physiological test levels).

Keeping this in mind, to increase testosterone in a normal healthy male via an alternative route which may have the risk of decreasing HPTA activity, only to stay within a normal physiological level (even if it is the upper end) is inviting the risk of a SARM(primarily MK-2866 aka ostarine) or light pro hormone (like low to moderate dosing a 4-DHEA derivative) without the gain. The risk is proportionate to the level of HPTA suppression which in turn be proportionate to the level of adrenal secretion. The more the adrenal secretes, the less the Hypothalamus needs to signal the pituatary to release LH for the testes. This is why this pathway is significant in women and not so significant in men.

Furthermore, to catalyze this release is a very tricky endeavor. You would have to create/find something that will selectively activate the cells in the zona reticularis responsible for producing androgens. And lets not forget the zona reticularis also produces DHT, DHEA and Androstenendione(Andro). If you increase DHEA or Andro you increase the risk of estrogen conversion.

I would equate the difficulty of something like this to the proported benefits of NO boosters. NO boosters in reality do not work to increase NO. If they actually increased systemic NO like they said claimed, people would be dropping dead or passing out from systemic hypotension. Blood vessels around the body would dilate and a cascade of negative effects would ensue. NO is tightly regulated by the body under normal phsyiological conditions. And to my knowledge there is no known supplement with a true mechanism of action to selectively increase NO in certain areas only (skeletal muscle).


Your thoughts USP? I understand my comments come off as negative criticism, but my desire is to engage in a biochemical and physiological discussion of the MOA of this new, unreleased product you are currently working on.

[mw1]

So this is pretty much just a promo thread for new USP product?

[mr.cooper69]

I have mixed feeling about this route of testosterone elevation. Allow me to elaborate in the attempt to have an analytical conversation.A physiological increases of testosterone in healthy males does not equate to significant gains in the gym. To my knowledge, in order to truly reap the benefit of an increase of testosterone, one would have to increase levels to supraphysiological levels (this is why hormonal supplementation works so well and testboosters can't compare even if they do indeed raise physiological test levels).Keeping this in mind, to increase testosterone in a normal healthy male via an alternative route which may have the risk of decreasing HPTA activity, only to stay within a normal physiological level (even if it is the upper end) is inviting the risk of a SARM(primarily MK-2866 aka ostarine) or light pro hormone (like low to moderate dosing a 4-DHEA derivative) without the gain. The risk is proportionate to the level of HPTA suppression which in turn be proportionate to the level of adrenal secretion. The more the adrenal secretes, the less the Hypothalamus needs to signal the pituatary to release LH for the testes. This is why this pathway is significant in women and not so significant in men. Furthermore, to catalyze this release is a very tricky endeavor. You would have to create/find something that will selectively activate the cells in the zona reticularis responsible for producing androgens. And lets not forget the zona reticularis also produces DHT, DHEA and Androstenendione(Andro). If you increase DHEA or Andro you increase the risk of estrogen conversion. I would equate the difficulty of something like this to the proported benefits of NO boosters. NO boosters in reality do not work to increase NO. If they actually increased systemic NO like they said claimed, people would be dropping dead or passing out from systemic hypotension. Blood vessels around the body would dilate and a cascade of negative effects would ensue. NO is tightly regulated by the body under normal phsyiological conditions. And to my knowledge there is no known supplement with a true mechanism of action to selectively increase NO in certain areas only (skeletal muscle).Your thoughts USP? I understand my comments come off as negative criticism, but my desire is to engage in a biochemical and physiological discussion of the MOA of this new, unreleased product you are currently working on.

I agree with the first part (hence why I said the pathway doesn't really matter in males). You are quite wrong on the topic of NO though. For instance, nitrates act as an NO donor in regions of hypoxia. So when you exercise and induce skeletal muscle hypoxia, nitrates/trites in circulation will convert to NO. Furthermore, there are many other ways to systemically increase NO. You wouldn't drop dead from hypotension because NO has a 1-2 second halflife and is limited by endothelial contact and intracellular regulation of the cGMP pathway. For instance, the body can upregulate phosphodiesterase and remove the vasodilation if needed. This is why PDE5 inhibitors are relatively contraindicated with nitrates...because they remove the body's ability to regulate systemic increases in NO levels.

[kisaj]

Science rules.

[GoHardOrGoHme]

Now this is going to be a good convo. I believe this is the first time we have entered into an intellectual conversation

You are quite wrong on the topic of NO though. For instance, nitrates act as an NO donor in regions of hypoxia. So when you exercise and induce skeletal muscle hypoxia, nitrates/trites in circulation will convert to NO.

Nitric oxide in cells acts as a strong second messenger in the signaling cascade associated with endothelial vasodilation. Nitric Oxide in specific is a second messenger in this cascade, to my knowledge NO(nitric oxide) is not a donor, it is a second messenger. Nitric oxide once produced by NOS will freely cross the cell membrane barrier where it binds to guanylate cyclase(GC). GC will then synthesize the cGMP which initiates another cascade to relax smooth muscle.

Circling back, NO itself is the result of a second messenger system. If you took a supplement that activated this system, it could not be specifically confined to skeletal muscle EVEN in the case of workout induced skeletal muscle hypoxia. You cannot selectively choose what the NO will bind to once in the blood stream. NO when used in a clinical setting causes systemic vasodilation.

Also the phsyiological effects of vasodilation due to exercise induced hypoxia happens independently of any supplementation. To further these effects is to imply that arginine is converted at an increased rate for a given period of time due to exogenous influences. There is no evidence to imply this occurs as a result of Nitric Oxide boosters. Furthermore clinical nitric oxide when administered has the side effect if abused can cause a detrimental decrease in blood pressure. This is why it is a contraindication to take viagra and RX nitric oxide for angina. The drop in blood pressure can be dangerous(and in some cases fatal)

Furthermore, there are many other ways to systemically increase NO. You wouldn't drop dead from hypotension because NO has a 1-2 second halflife and is limited by endothelial contact and intracellular regulation of the cGMP pathway.

For instance, the body can upregulate phosphodiesterase and remove the vasodilation if needed. This is why PDE5 inhibitors are relatively contraindicated with nitrates...because they remove the body's ability to regulate systemic increases in NO levels.[/QUOTE]

You must realize the clinical dose for nitroglycerin is .4 to .8mg per lingual spray and about .3 to .6mg per tablet. The effects last about 5 minutes. If you think about this in light to the 1-2 second half-life it doesnt make sense. Unless you factor into the fact that upon administration of this very small amount of nitroglycerin, you have actually activated a second messenger cascade. What do you think would be the systemic effects of taking a TRUE nitrodilator at doses of 500mg?

And your statement about PDE5 inhibitors...i disagree with. PDE5 does not regulate nitric oxide levels, it regulates cGMP levels. As a matter of fact PDE5 inhibitors are used for erectile dysfunction for there ability to prevent cGMP degradation...not NO.


Vasodilation is commonly removed via MANY mechanisms. The most notable is sympathetic activation via alpha adrenergic receptors. This is how pressers work in the cases of hypotension resulting in septic shock. Systemic vasodilation will activate the sympathetic nervous system to increase the HR and increase vascocontristion via baroreceptor mediated reflexes. It is my understanding PDE5 inhibition is not the primary means of offsetting systemic vasodilation, which would be caused by nitrodilators. The baroreceptor relfex will kick in before this happens.

Therefore I politely disagree with your statement that I am quite wrong on the issues of NO. However I do see that there may be a level of misunderstanding between us on the subject of Nitric Oxide supplements.

[mr.cooper69]

What's your background?

I never said NO is a donor btw. Nitrates are an NO donor. NO also isn't a second messenger. It's a "first messenger." The 2nd messenger is cyclic GMP.

You can indeed selectively direct NO. Again, it has a 1-2 second halflife. If nitrates convert to NO during a state of hypoxia local to skeletal muscle, that NO diffuses rapidly across the endothelium and acts there and there alone. Its halflife limits escape from this location.

NO isn't used in a clinical setting. And the reason is again because of the halflife. Instead, we use the exact same things I just described: nitrates and, emergently, IV nitroprusside. You can read more on a basic wiki page: http://en.wikipedia.org/wiki/NO-releasing_drug. If all these drugs couldn't locally induce NO production or release, then yes, you'd go into hypotensive shock. So again, selective vasodilation and NO donation/release is very common and certainly doable.

You keep mentioning nitric oxide, but as I said above, we don't give nitric oxide clinically. The contraindication for viagra (a PDE5i) and nitrates were explained in my previous post, as you lose one of the most powerful feedback mechanisms on NO-induced vasodilation. The effect is synergistic, not additive.

As for the nitroglycerin, you're off again on clinical applications. Most nitrates are administered via patch in a 12 hour on-12 hour off fashion. The drugs you are citing are used for emergent conditions or acute/unstable angina.

PDE5 inhibitors do regulate NO through the same exact mechanism that NO regulates vasodilation.

NO->cGMP->GMP with PDE regulating the final step. Hence, the activity of NO is regulated by PDE. You know that's what I meant since that's the topic of this discussion.

PDE isn't the primary mechanism for combating systemic hypotension; it is a prominent mechanism for combating NO/cGMP-induced vasodilation. Please note that these concepts are not one and the same. You are fairly spot on with the autonomic nervous system, starting with reflex tachycardia + baroreceptor reflex, but progressing to further mechanisms in shock like capillary auto-transfusions and a massive release from the RAAS system of the macula densa.

In light of these points, I do still believe you are wrong in your assessment of NO. But unlike other disagreements I have on this forum, I respect you very much for at least knowing your stuff prior to engaging into discussion, and not simply alluding to anecdote or logs. So kudos to you for that. I unfortunately won't be able to give a "long" reply for quite some time as I have finals and boards to study for, but you can always me at [email protected] and we can discuss whatever you please.

[GoHardOrGoHme]

No worries. You wont need to have a long response to this.

I apologize I can see that misread your message as stating as NO being the donor when you specifically referred to nitrates being a donor. That is my mistake.

As far as NO being a "first messenger" really depends on what part of the cascade you are looking at. If you look specifically at the intracellular production of cGMP then yes I agree. However IP3 activates NOS which then produces NO. IP3 is the product of the adenylate cyclase cascade via activation of phospholipase C. The only true first messenger in this cascade would be the original hormone/protein/external signaling molecule to bind to the initial receptor which triggers the G-coupled protein cascade. However I will not disagree with it being considered a first messenger of intracellular cGMP pathway which begins when NOS is sitmulate by IP3. On this point we would be arguing semantics which is really not that big of a deal in my opinion since im not a biochemist lol.

I can see we are talking about two different things in one point. My emphasis was NO boosters touted by many pre-workouts(which i do admit my presentation was sloppy and aludded to something that you correctly pointed out as being inaccurate).

As far as a selective NO. I concede ignorance. I am unaware of it therefore cannot comment on that point. What I was tought about IV nitroprusside, nitroglycerin, and other drugs is that they had systemic effects via alpha adrenergic receptor activation. Now being that I obviously have only part of the whole truth, I can easily concede that what you are presented is a more complete picture. Still havent taken the pharm block yet and the pharm I have is introductory at best.

Nitric oxide is given clinically in the form of gas. Nitrates are not the same and the fact i equated the two is my error. Nitroglycerin is not NO and I made a mistake, should looked up my facts before posting them. You are right.

In my post i stated that the dose of nitroglycerin...not when its used. You are absolutely correct in that nitro is given in the setting of unstable/acute angina. And it was my error I equated nitroglycerin which is a nitrate to NO. This is again my error.

I agree with your comment and statement on PDE5 inhibition and the activity of NO/PDE.

I really want to argue that I wasnt wrong, but clinically and factually I must concede BEING that I made a grave error in my reasoning. Kudos to you coop. I accept your statement that I was off on my assement of NO. Thank you for keeping it classy. Cheers.

...(lol) However I will stand by the intention of my original statement Clinical nitrates are not the same as supplement NO boosters (I dont want to name brands or supplements). And I still believe that taking a NO booster supplements does not clinically yield the claims of increased NO productions to increase muscle pumps. Can some of the ingredients of other effects that will increase workout intensity/effectiveness yes. But increasing a pump via NO production...im not buying into that yet. Im also not sure about taking supplements that supposedly contain nitrates (creatine nitrate, arginine nitrate, potassium etc etc)

Agmatine and Citrulline...this is another discussion all together. Though they are touted as NO boosters, I believe their benefits extend far beyond any NO boosting ability they may have.

However given the appropriate data I will gladly change my opinion.

[T-Bone]

NERDS!

[GoHardOrGoHme]

NERDS!

And proud of it!