Time period in which exogenous GH shuts down endogenous release->nandi,others PLEASE

Re: Time period in which exogenous GH shuts down endogenous release->nandi,others PLEASE

Posted by: notatrase

If for only 6 hours, administration should occur in plateaus of endogenous GH release

Time of plateaus occuring at approximately 7am and 1-2pm

The human response to exogenous GH is really variable, as can be seen in figures 1 and 2 in this study.

To quote from the paper:

Although the mean serum 22K-GH levels after injection were not different even at higher doses compared to the placebo group during the first 4 h, the 22K-hGH levels were reduced even at lower doses from approximately 4�6 h up to 12 h. During the subsequent 24-h observation period, the 22K-hGH levels gradually returned to the placebo level.

So suppression does not even begin until 4 hours after injection, and can last for many hours after that, as the abovementioned figures show. The reason there is a lag of a few hours is because it takes several hours for IGF-1 (which suppresses GH) to rise after a GH injection. See fig 4.

The lower figures of 4 to 6 hours of suppression after an injection are from rat studies:

In previous studies (31, 32), single intramuscularly or sc administration of HGH(with monitoring of the resulting plasma profiles) showed a delayed and prolonged suppressive effect on rat GH secretion. The time course of endogenous GH suppression in rats was similar to but faster than that in humans reported here. The fast time course in rats was probably due to the rapid absorption of hGH in this species (14, 33).

Posted by: Nandi12

The human response to exogenous GH is really variable, as can be seen in figures 1 and 2 in this study.

To quote from the paper:

Although the mean serum 22K-GH levels after injection were not different even at higher doses compared to the placebo group during the first 4 h, the 22K-hGH levels were reduced even at lower doses from approximately 4�6 h up to 12 h. During the subsequent 24-h observation period, the 22K-hGH levels gradually returned to the placebo level.

So suppression does not even begin until 4 hours after injection, and can last for many hours after that, as the abovementioned figures show. The reason there is a lag of a few hours is because it takes several hours for IGF-1 (which suppresses GH) to rise after a GH injection. See fig 4.

The lower figures of 4 to 6 hours of suppression after an injection are from rat studies:

In previous studies (31, 32), single intramuscularly or sc administration of hGH (with monitoring of the resulting plasma profiles) showed a delayed and prolonged suppressive effect on rat GH secretion. The time course of endogenous GH suppression in rats was similar to but faster than that in humans reported here. The fast time course in rats was probably due to the rapid absorption of hGH in this species (14, 33).

Excellent, Nandi!
Nandi, would you please suggest YOUR thoughts on optimal timing of dosing? Based on the studies in humans, it should not even matter, correct?

Also, Nandi, at a low dose of 2iu/day, would you suggest dosing twice daily with 1iu or dosing with a single 2iu shot? I know that you are not the biggest GH fan, but I am sure you have thoughts on this.

I am sure your highly-evolved alien brain will provide further enlightenment
Thank you, sir

It's hard to say if time of injection really mattered in a normal person. GH deficient kids grow better when they get their injection at night, presumably because that mimics more closely the natural bedtime GH pulse.

There are two schools of thought (or 3 if you consider the school that holds there is no difference). One line of reasoning holds that if you take the GH right before bed, since it takes about 4 hours for suppression to set in, you very well may get your natural bedtime pulse and the exo pulse. In fact you can see this in some of those graphs.

The other school says take it very early in the morning, say at 6 AM. Suppose you go to bed at 11 PM and you get your normal pulse around midnight or so. That leaves 18 hours between your morning shot and the time your pulse should occur. That may very well be long enough for the morning shot to wear off so you still get your bedtime pulse, and your exo morning pulse, giving you a more steady 24 hour elevated GH level. This second theory makes sense to me and is worth trying, especially with a relatively low GH dose, like 2 IU, which is more likely to wear off by bedtime.

I've changed my mind several times in this regard. Currently I think the early AM might be the best time, and just do one injection.

I wish I had some hard data for you rather than speculation.

With a big dose it likely may not matter either way

Posted by: Nandi12

I wish I had some hard data for you rather than speculation.

With a big dose it likely may not matter either way

Nandi, your speculation IS hard data in my book!!
Thank you, sir.

So if one taking 2iu/day works out in the morning, he/she should take the 2iu upon waking. He/she should workout and then administer the proper insulin (humalog) dosage post-workout. Sound right in your freakin golden opinion?

Would taking 1iu upon waking and 1iu before bed be plausible? Or would this defeat the whole purpose?

The 2iu single administration is probably the way to go, yes?

Two injections would probably be just fine as well, and would probably give you the most uniform blood levels. But would you benefit more from a single larger injection? I honestly don't know.

One study that throws insulin into the mix has always bugged me and I have never found other research to back it up. It showed that GH clearance rate increases with insulin levels (1). This has always made me kind of question the wisdom of taking GH and insulin around the same time. Maybe if you are going to use insulin it might be better to go with the GH at night, or at least make sure you leave a few hours between GH and slin shots. It is starting to get pretty complicated now, and maybe it's best not to worry too much.

I think I like your idea of two small shots, except for this insulin thing...

(1) J Clin Endocrinol Metab 2002 May;87(5):2185-93

Body composition and circulating levels of insulin, insulin-like growth factor-binding protein-1 and growth hormone (GH)-binding protein affect the pharmacokinetics of GH in adults independently of age.

Hansen TK, Jorgensen JO, Christiansen JS.

i have been testifying to bedtime shots for 2 yrs now as well as the fact that natural gh is suppressed for about 24hours...

Thank you for finding that study Nandi.. it was terrific!!!

FINALLY one on humans and not rats!!!

you will help me sleep better for sure now ahahhahha

so IMO if recovery and healing is the main goal shots should be done at nighttime..
OR i like the idea of morning and bedtime to keep levels more constant...
slin is always best post workout prior to meal... if 2x a day i would say morning shot pre-breakfast...

did you find the answers you need Notatrase??

Thank you, SG for your response!
My knowledge-gathering is almost complete, but new questions have arisen as consequence of Nandi's comments regarding increased clearance time when used in conjunction to insulin.
Everyone seems to believe that insulin is an ESSENTIAL addition to a GH cycle--that the full potential of GH cannot be had in insulin's absence; I guess it is thought of as somewhat of an essential synergism.

What is your take, guys?
Perhaps if I go into my goals, you will better be able to advise me.
Let us say that I, in theory, were coming off of a cycle of:
50mg tren/day (100mg/day at start of cycle)
25mg Test Prop/day
75mg winny/day
5gm of andractim/day

Using GH (and maybe ins as a LONG bridge), I would like to stay lean and stay at about the same bodyweight and muscularity (if possible). I am not TOO far above my genetic potential.
I am following a CKD, similar to that of JGUNS (THANKS, JG!!).

Now, based on my goals, can you suggest a best method of administration?
Can the diet remain the same, or should I alter it in any ways to accomodate the GH?
I will begin taking it during post-cycle recovery; will Nolvadex hinder its effects? Suggestions?
Based on my goals, should insulin be added (I assume that it will be necessary to maintain muscle fullness in the absence of androgens, yes?)?

So far, this is what i am thinking: What would you guys change?
6:00am wake up-->1iu GH
6:30am workout
7:30am-------------->a few iu insulin (please know that I am exp.with ins) (IS this too soon after the GH inj?)

9-10pm bedtime--->1iu GH

If you guys could come up with a weak melatonin agonist that antagonized endo melatonin release at night, but still had enough
effect to set your bodies circadian rythm, you could in theory extend the effectiveness of exo GH.

1: J Pineal Res 1986;3(1):55-66 Related Articles, Links

Effects of pineal indoles and arginine vasotocin on lipolysis and lipogenesis in isolated adipocytes.

Ng TB, Wong CM.

The effects of arginine vasotocin and the pineal indoles melatonin, serotonin, N-acetylserotonin, hydroxytryptophol, methoxytryptophol, hydroxyindoleacetic acid, methoxyindoleacetic acid, and methoxytryptamine on lipolysis and lipogenesis in isolated adipocytes were studied. Basal lipolysis was inhibited by all the indoles tested at a dose of 1 mumole except hydroxytryptophol. Methoxytryptamine and serotonin inhibited hormone-induced lipolysis in a dose-dependent manner and exhibited the highest antilipolytic activity in isolated rat, rabbit, and hamster adipocytes. However, their antilipolytic activity could not be overcome by increasing the dose of the lipolytic hormone. Dibutyryl cyclic AMP-induced lipolysis was also inhibited. All the pineal indoles tested were capable of suppressing basal and insulin-stimulated lipogenesis in the dose range 0.33-3 nmole. At lower doses there was no effect. Arginine vasotocin at a dose of 25 nmole significantly augmented basal lipogenesis.

PMID: 3958894 [PubMed - indexed for MEDLINE]

Melatonin inhibited BASAL lipolysis in adipocytes.

i.e it stopped fat burning at night..

By how much?

Check this out:

1: Endocrinology 2001 Sep;142(9):3783-90 Related Articles, Links

Inhibition of isoproterenol-induced lipolysis in rat inguinal adipocytes in vitro by physiological melatonin via a receptor-mediated mechanism.

Zalatan F, Krause JA, Blask DE.

Laboratory of Experimental Neuroendocrinology/Oncology, Bassett Research Institute, Cooperstown, New York 13326, USA.

Check:

Because the pineal hormone melatonin has been implicated in affecting adiposity in rats and fatty acid transport in certain rat tumor models, we tested whether melatonin regulates lipolysis in a normal cell system in vitro. Adipocytes were isolated from the inguinal fat pads (i.e. sc fat) of Sprague Dawley male rats during mid-light phase.

Here:

Lipolysis was stimulated with isoproterenol (3 microM), and cells were incubated for 4 h in the presence or absence of a physiological circulating concentration of melatonin (1 nM). Lipolysis was measured by determining the amount of glycerol present in the incubation buffer, expressed as nmol glycerol/mg cellular fatty acid. We observed a 20- to 30-fold stimulation of basal lipolysis by isoproterenol, and this stimulation was inhibited 50--70% by melatonin. Melatonin exhibited this effect over a wide range of concentrations tested (100 pM-1 microM) with an IC(50) of approximately 500 pM. The effect by melatonin (1 nM) was completely blocked by pertussis toxin (50 ng/ml), by 8-bromo-cAMP (10 nM), and by the melatonin receptor antagonist S-20928 (1 nM). These results suggest that the antilipolytic effect occurs through one of the G(i) protein-coupled melatonin receptors because we have shown that both the mt(1) (Mel 1a) and MT(2) (Mel 1b) melatonin receptors are expressed in inguinal adipocytes. Melatonin inhibition of lipolysis was not observed in adipocytes isolated from rat epididymal fat pads (i.e. visceral fat), even though these cells also express both the mt(1) and MT(2) receptors. The results indicate that physiological circulating concentrations of melatonin inhibit isoproterenol-induced lipolysis in rat adipocytes via a G protein-coupled melatonin receptor-mediated signal transduction pathway in a site-specific manner.

PMID: 11517154 [PubMed - indexed for MEDLINE]

Looks to me like melatonin is incredibly lipogenic. Makes sense as the body releases GH at night which is lipolytic.
Problem is, you need melatonin. For your circadian Rythm to work properly and as a brain anti-ox.

But what about a weak melatonin agonist?

It would function like tamoxifen does on estrogen receptors.
It would reduce the total up-take of melatonin, by blocking the endo melatonin from latching on, while still being a weak agonist to the receptor and therefore not screwing up your circadian rythm and still promoting some of its anti-ox prowess. GH levels would rise at night and then you would boost lypolisis even further by blocking the melatonin feedback loop.

In normal people, GH levels would rise at night.....increasing lipolysis.....but then you would boost lypolisis even further by blocking the melatonin feedback loop.

AND, the same thing would happen with people using exo GH. In essence extending its effectiveness.

This of course is completely theoretical at the present time.

Fonz

ehhhhh???

Posted by: notatrase

ehhhhh???

Its a bit complicated, but I'll simplify.

There's always an up and down.

At night, when you fast, the pineal gland secretes melatonin.(Signaling that you're about to go into sleep mode)

This INCREASES insulin sensitivity in the adipocytes and reduces lipolysis.

Imagine this as the DOWN.

Then, at night the body releases GH which is lipolytic and repairs tissues.

This INCREASES lipolysis.

Imagine this as an UP.

Now, what happens if you could "fool" the body into thinking the body had already secreted melatonin?

The adipocytes sensitivity to insulin would be REDUCED at night when compared to normal.

Result, is a reduced DOWN.

Since you have just decreased lipogenesis, you have in fact increased overrall lipolysis.

Simplistic and theoretical? Yes.

But it is interesting nontheless IMO.

Fonz

interesting, indeed, Fonz.

Do you have any advice to give pertaining the questions and regimen that I have posed? I would value your input, bro.

Since you're bridging, maintining levels of circulating GH more constant makes more sense.

1IU 2X/day AM and PM.

Fonz