GH and The Athlete - is there a point to it???

[majutsu]

In other words, these two studies, plus everything else we have here, enable us to go back to your original question: Gh for the athlete? For the strength athlete, minimal benefit. For example, in the study with normals and GHD subjects, the benefit was minimal for measures of hypertrophy and strength used in that study. Some subjects showed benefit only when IGF somehow coincidentally rose. But titrating GH for IGF raise per se was not helpful as a therapeutic measure overall in either group.

In the other study, though involving GHD subjects, we see in all probability that in all subjects GH converts the body to a fat-burning based metabolism rather than a glucose-burning based metabolism. So GH would burn fat.

For power athletes and athletes in general, the benefit of GH would be a fraction of that more cheaply obtained by anabolics. However, if the athlete is in a tested sport, GH rises alot further up the list, and if the testing is random, GH and insulin rise to the top of the list.

For bodybuilders, tested or no, the fat burning of GH would doubtless contribute to the overall aesthetic effect desired. At low doses even, certainly at 2u ed, the body is converted to a fat burning metabolism, subtly starting even at week 1! This would make it one of the most effective and even affordable fat burners, as other substances cannot boast a complete metabolic overhaul at such low doses. The average kit could last 2 months at this dose. This could be done throughout a few anabolic cycles, or coupled with T3 and other substances for an extreme cutting cycle.

This would seem to be the consensus here.

 

[Juice Authority]

In other words, these two studies, plus everything else we have here, enable us to go back to your original question: Gh for the athlete? For the strength athlete, minimal benefit. For example, in the study with normals and GHD subjects, the benefit was minimal for measures of hypertrophy and strength used in that study. Some subjects showed benefit only when IGF somehow coincidentally rose. But titrating GH for IGF raise per se was not helpful as a therapeutic measure overall in either group.

In the other study, though involving GHD subjects, we see in all probability that in all subjects GH converts the body to a fat-burning based metabolism rather than a glucose-burning based metabolism. So GH would burn fat.

For power athletes and athletes in general, the benefit of GH would be a fraction of that more cheaply obtained by anabolics. However, if the athlete is in a tested sport, GH rises alot further up the list, and if the testing is random, GH and insulin rise to the top of the list.

For bodybuilders, tested or no, the fat burning of GH would doubtless contribute to the overall aesthetic effect desired. At low doses even, certainly at 2u ed, the body is converted to a fat burning metabolism, subtly starting even at week 1! This would make it one of the most effective and even affordable fat burners, as other substances cannot boast a complete metabolic overhaul at such low doses. The average kit could last 2 months at this dose. This could be done throughout a few anabolic cycles, or coupled with T3 and other substances for an extreme cutting cycle.

This would seem to be the consensus here.

I would have to agree with you on all your points. The only issue that still remains in my head anyway is whether the combination of GH and T3 is beneficial for fat burning. If T3, even at a low dose (25mcg), nullifies the effect GH has on the beta-3 receptor I would think it would be counterproductive for fat burning but I'll defer to DrJMW's explanation of it.

 

["Z"]

I would have to agree with you on all your points. The only issue that still remains in my head anyway is whether the combination of GH and T3 is beneficial for fat burning. If T3, even at a low dose (25mcg), nullifies the effect GH has on the beta-3 receptor I would think it would be counterproductive for fat burning but I'll defer to DrJMW's explanation of it.

GH has no effect on the Beta-3 receptor. What it does is increase lipolysis by modifying your fat cells response to cortisol. Making them more sensitive to it. True Beta-3 drugs are still in the preliminary stages of development.

 

[Juice Authority]

GH has no effect on the Beta-3 receptor. What it does is increase lipolysis by modifying your fat cells response to cortisol. Making them more sensitive to it. True Beta-3 drugs are still in the preliminary stages of development.

It is not directly mediated through the beta 3 receptor but it's the only known drug (to my knowledge anyway) that "stimulates" the beta-3 receptor. Now I've been trying to figure how exactly it stimulates the beta-3 if it's not mediated through it. Have you read the studies I posted on this thread and seen some of DrJMW's comments?

 

[Whacked]

GH and OBESITY
by Nandi

INTRODUCTION

The observation that growth hormone (GH) secretion is impaired in obesity, and is reversible upon weight loss, has prompted a great deal of research that has helped us understand how GH acts on adipocytes to regulate lipolysis and lipogenesis. Reciprocally, we are beginning to understand how adipocytes, as secretory organs, contribute to the regulation of GH secretion. The impaired secretion of GH in obesity, as well as the predominantly lipolytic effects of GH has prompted a number of studies where GH has been successfully used to induce significant weight loss in obese patients.

In this brief overview, I’d like to first look at the effects of GH on adipocyte function, then address the converse subject of adipocyte regulation of GH secretion, with particular emphasis on how obesity impairs GH secretion. Finally, we will look at how GH has been used therapeutically to treat obesity.

PHYSIOLOGICAL EFFECTS OF GH ON ADIPOCYTES


Two enzymes active in adipocytes which are of paramount importance in regulating lipogenesis (fat accumulation) and lipolysis (the breakdown of stored triglycerides into free fatty acids [FFA]) are lipoprotein lipase (LPL) and Hormone Sensitive Lipase (HSL); both are affected by GH. The accumulation of triglycerides in adipose tissue is controlled primarily by LPL. Triglycerides are transported to fat cells for storage in the form of very low-density lipoproteins (VLDL) and chylomicrons. LPL is synthesized by adipocytes and then secreted to the intracellular space, after which it attaches to the luminal portion of the vascular endothelium of the vessels supplying the adipocytes. There it hydrolyzes the triglyceride fraction of the VLDL and chylomicron particles, releasing FFA that are taken up by adipocytes. GH has been shown to have an inhibitory effect on adipose LPL (1,2), with a more pronounced reduction of LPL activity in intra-abdominal fat deposits than in subcutaneous fat (3). Exactly how GH inhibits LPL is unclear. GH treatment does not seem to affect LPL gene expression or mRNA levels, so it is assumed that the effect is post-translational, with GH somehow interfering with the activity of the enzyme (1). In any case, the net effect is that GH reduces the uptake of free fatty acids by fat cells, a clear antiadipogenic effect.

It should be noted that a number of other hormones affect LPL activity in significant ways. Insulin is the hormone with the greatest ability to stimulate LPL activity, contributing to the well-known lipogenic effect of this hormone. Conversely catecholamines (e.g. epinephrine) are strong downregulators of LPL, contributing to their ability to block fat accumulation. Testosterone and estrogen both inhibit LPL, contributing to their fat burning properties (4).

The second enzyme that dominates adipocyte metabolism is Hormone Sensitive Lipase (HSL). HSL is responsible for the hydrolysis of stored triglycerides to glycerol and free fatty acids. Thus hydrolyzed, the FFA can leave the adipocyte and travel in the blood to other tissues where they can be used as fuel, primarily in working muscle (As with fats entering adipocytes, the glycerol portion of the triglyceride must be removed in order for free fatty acids to leave the fat cell). GH amplifies the action of HSL in two ways. First, HSL is activated by catecholamines that act as agonists at beta 1, beta 2, and possibly beta 3 receptors in adipocytes. This is how sympathomimetic drugs like ephedrine and clenbuterol stimulate fat burning: they act as beta agonists to stimulate HSL. GH has been shown to be capable of inducing beta 2 receptors in adipocytes; more beta 2 receptors mean more HSL activity (5). As an aside, this is one way androgens promote lipolysis as well, via the upregulation of beta adrenoreceptors. Beta receptors employ the “second messenger” cyclic AMP (cAMP) to relay their signal within the cell that ultimately activates HSL. The signal is terminated by the enzyme phosphodiesterase. GH has been shown to have the ability to block phosphodiesterase, prolonging the activity of HSL (5). So we see GH promotes lipolysis via HSL by two routes: it upregulates the receptors that activate HSL, and it prolongs the signaling that keeps HSL functioning.

Besides affecting the metabolic functioning of adipocytes, GH controls adipocyte differentiation and proliferation. Differentiation refers to the process whereby immature preadipocytes activate the genes that direct them onto the path to becoming fully functioning mature adipocytes capable of carrying out the metabolic and secretory processes described above, as well as storing lipids. Proliferation refers to the increase in cell number via repeated cell division. The actions of GH are mixed here. We know that GH stimulates the hepatic production of Insulin-like Growth Factor 1 (IGF-1), which is responsible for many of the metabolic and perhaps anabolic actions of GH. It has been shown that IGF-1 is capable of stimulating the proliferation of preadipocytes, increasing the pool of potential adult fat cells (6). On the other hand, GH itself inhibits the differentiation of these precursor cells into adult adipocytes. Despite these contradictory effects of GH/IGF-1 on adipocyte proliferation and differentiation, the net effect of GH treatment in obese subjects in a number of studies is one of reduced adiposity.


FREE FATTY ACIDS AND GH SECRETION


GH and FFA function together in a regulatory feedback fashion. We have seen above how GH stimulates lipolysis, resulting in elevated levels of FFA. FFA in turn act back in a negative feedback manner to inhibit GH secretion. Circulating free fatty acids, elevated in obesity, are thought to be partly responsible for the suppression of GH seen in this condition (Plasma levels of FFA are elevated in obesity primarily because a greater than normal amount of FFA is released from the expanded adipose tissue mass even though the rate of lipolysis from individual fat cells appears to be normal).

It is generally accepted that circulating FFA rapidly partition into the plasma membranes of pituitary cells which secrete GH. This is believed to alter the function of proteins embedded in the plasma membrane, perturbing intracellular signaling and inhibiting GH release (9). Animal studies have shown that FFA are also capable of acting directly on the hypothalamus to increase the release of somatostatin, with a resulting inhibitory effect on GH release. It is controversial whether this hypothalamic effect exists in humans (10). No known stimulus for GH release seems to be able to escape the suppressive effects of elevated FFA. As just one example of relevance to athletes, exercise is a well-known stimulus for GH release. Seemingly paradoxically, exercise also elevates FFA acid levels, as lipolysis increases in order to supply FFA to muscle to serve as a fuel source. However, when nicotinic acid, a potent inhibitor of FFA release from adipocytes is administered during exercise, the low FFA levels resulting from nicotinic acid feeding were associated with a 3- to 6-fold increase in concentrations of human growth hormone throughout exercise. Exercise performance was also negatively impacted by the lack of availability of FFA as a fuel substrate (11). This could have practical implications for anyone using nicotinic acid to elevate HDL cholesterol levels, as many anabolic steroid using athletes are known to do (Anabolic steroids in general, and oral 17 alpha alkylated steroids in particular, are known to significantly lower HDL, or “good” cholesterol).

Somewhat surprisingly, in light of the evidence discussed above that FFA inhibit GH release, GH secretion is increased during fasting both in obese and normal subjects after administration of GHRH, despite an increase in fasting related FFA levels. This has been cited as contradictory to the theory that FFA impair GH secretion in obesity (12). However, as mentioned above, ghrelin may be more important than GHRH in stimulating GH release during fasting. While FFA do reduce the ability of ghrelin to stimulate GH release, ghrelin is partially refractory to this inhibitory effect of FFA. So it is possible that the results described in (12) were confounded by the effects of ghrelin on GH during fasting.

In any case, GH is generally low in obesity, and as a consequence there is a loss of the usual lipolytic effect of GH seen in normal individuals. This has prompted the experimental use of GH to attempt to reverse obesity in a number of studies.



INCREASED GH CLEARANCE RATE IN OBESITY


Studies have shown besides decreased production of GH in obesity, GH clearance rates are increased as well. While not necessarily being an effect directly attributable to the action of adipocytes on GH, it does contribute to lower overall GH plasma levels (13). Not well understood, this phenomenon has been attributed to either increased glomerular filtration of GH, changes in liver metabolism, or accelerated processing by excessive body fat stores.



EFFECT OF ADIPOSE TISSUE ON IGF-1


Despite the fact that GH levels are typically depressed in obesity, total serum IGF-1 levels are normal or high, and free IGF-1 levels are consistently elevated (5). This may seem surprising since—as discussed above—IGF-1 is normally produced in the liver under the stimulus of GH. One might expect the opposite to be observed: low GH in obesity leading to low circulating IGF-1. However, the observation that IGF-1 mRNA levels in fat cells are nearly as high as those found in the liver has led to the suggestion that adipocytes could contribute significantly to circulating levels of IGF-1 (5). If this is the case, then the normal negative feedback of IGF-1 on GH secretion could contribute in part to the depressed levels of GH seen in obesity. Adipocytes seem to secrete IGF-1 in response to GH, and in obesity, individual fat cells may secrete less IGF-1 than in normal subjects. The net overall effect of the increased number of fat cells in obese subjects would offset this, leading to the observed elevation in IGF-1. The depressed GH due to elevated IGF-1 in obesity provides another rationale for the use of GH to treat obesity.



INHIBITION OF GH SECRETION AND SIGNALING BY INSULIN


Insulin resistance and hyperinsulinemia are often associated with obesity. Research has shown that both normal physiological levels of insulin (14) as well as obesity-associated hyperinsulinemia blunt the GH response to GHRH and may contribute to the GH deficiency seen in obesity (15). Although the exact mechanism by which insulin regulates GH secretion is not known, a number of possibilities exist. Specific insulin binding sites have been found in both rat and human anterior pituitary adenoma cells. Inhibition of GH synthesis and release, and suppression of GH mRNA content, has also been observed when pituitary cells are exposed to insulin. So insulin could have a direct inhibitory effect on the pituitary. Insulin receptors are also present in the hypothalamus, so it is possible insulin is acting there. It has also been suggested that insulin could inhibit GH release by lowering plasma amino acid levels, since amino acids stimulate GH release. It has also been observed that insulin lowers circulating levels of the potent GH secretagogue ghrelin (16).

In vitro, insulin has also been shown in nonhepatic tissue to block the translocation of the GH receptor from the cytosol to the cell surface, with the effect of inhibiting binding of GH to its receptor. This may be another way hyperinsulinemia associated with obesity disrupts GH signaling (17)



GROWTH HORMONE THERAPY TO TREAT OBESITY


We have discussed a number of reasons why GH might potentially be of therapeutic use in the treatment of obesity due to its lipolytic action. Nevertheless, the results of trials have been inconsistent. This inconsistency, coupled with side effects of treatment which include insulin resistance, edema, arthralgia, and carpel tunnel syndrome to name a few, has prompted some critics to take a strong stand against the use of GH to treat obesity:



OBJECTIVE: To summarize the reports in the literature regarding the effect of growth hormone (GH) treatment of obesity. RESEARCH METHODS AND PROCEDURES: Clinical trials of GH treatment of obese adults were reviewed and summarized. Specifically, information regarding the effects of GH on body fat and body fat distribution, glucose tolerance/insulin resistance, and adverse consequences of treatment were recorded. RESULTS: GH administered together with hypocaloric diets did not enhance fat loss or preserve lean tissue mass. No studies provided strong evidence for an independent beneficial effect of GH on visceral adiposity. In all but one study, glucose tolerance during GH treatment suffered relative to placebo. CONCLUSION: The bulk of studies indicate little or no beneficial effects of GH treatment of obesity despite the low serum GH concentrations associated with obesity (18).


Despite the harsh tone of these investigators, a number of studies have shown a positive effect of GH on fat loss, with the abovementioned side effects being reversible upon termination of treatment. Additionally, countless anecdotal reports by bodybuilders and athletes contribute to the evidence that GH can be efficacious for fat loss.

In stark contrast to the assessment of the GH trials in (18) are reports by Lucidi et al (19) and Nam et al (20) that cite a number of studies where “GH is effective in reducing fat mass, especially visceral fat” (20). Nam et al discuss why some studies may have shown negative results. In their paper, the authors reported significantly enhanced fat loss (1.6 fold) compared to placebo, with a greater loss in visceral fat and an increase in lean body mass (20). Kim et al used low dosages of GH (0.18 U/kg Ideal Body Weight/week) and a hypocaloric diet, and believed this accounted for at least part of the success of their trial. They point out that one of the well known and dose dependent side effects of GH administration is insulin resistance and hyperinsulinemia. Insulin is well known to be an adipogenic hormone, and the hyperinsulinemia that often accompanies GH treatment could offset the lipolytic effect of the administered GH. To quote from the authors,



In addition, as the product of GH-induced lipolysis, FFA has been considered to be the principle factor in peripheral insulin resistance. These findings suggest that GH-induced hyperinsulinemia may antagonize the lipolytic effect of GH. In our study, GH treatment did not induce a further increase in insulin levels. [This] suggest that although GH might induce insulin insensitivity and hyperinsulinemia, low-dose GH therapy with diet restriction in obesity could overwhelm the antilipolytic action of insulin.

The frequency of side effects depends on the dose of GH. We observed only minor side effects which spontaneously subsided, indicating that the dose of GH in this study was lower in comparison with other studies (20).


So it may very well be that many of the studies that failed to demonstrate weight loss after GH administration employed excessively high doses, which either aggravated pre-existing hyperinsulinemia or subsequently induced hyperinsulinemia, which offset any lipolytic effects of GH.

We have discussed a number of ways by which GH promotes lipolysis, the main effect being to stimulate Hormone Sensitive Lipase in adipocytes. But lipolysis, the term used to describe the mobilization of fatty acids so that they can potentially be used as fuel, is not the same thing as the actual oxidation of those fatty acids for energy in muscle tissue. Perhaps the failure of some trials to show fat loss during GH treatment is a result of a failure to oxidize the lipids that GH makes available as a potential fuel source. This seems not to be the case however, as research has shown that GH actually increases lipid oxidation at the expense of glucose oxidation by activating the so called glucose-fatty acid cycle where the preferential use of fat as a fuel substrate inhibits the use of glucose as fuel (21) (This process actually provides a mechanistic explanation of how GH administration induces insulin resistance: when more fatty acids are used as fuel, cells take up less glucose for use as a fuel substrate, leading to glucose intolerance). In addition to promoting the preferential use of fat as a fuel substrate by increasing its availability through enhanced lipolysis, GH also appears to directly stimulate the oxidation of lipids, perhaps by upregulating key mitochondrial enzymes involved in lipid oxidation (22).

Moreover, another well-known effect of growth hormone is to slow skeletal muscle breakdown during fasting (23). Teleologically speaking, the body secretes GH during periods of caloric restriction in an attempt to preserve skeletal muscle at the expense of increased fat oxidation for fuel. So during periods of caloric restriction, GH is responsible for less reliance on glucose and protein for energy, with fat being preferentially oxidized.



References

(1) J Endocrinol Invest. 1999;22(5 Suppl):10-5 Effect of growth hormone on adipose tissue and skeletal muscle lipoprotein lipase activity in humans. Richelsen B

(2) J Endocrinol Invest. 1999;22(5 Suppl):2-9 Effects of growth hormone on lipoprotein lipase and hepatic lipase. Oscarsson J, Ottosson M, Eden S.

(3) J Endocrinol. 1993 May;137(2):203-11. Influence of growth hormone deficiency on growth and body composition in rats: site-specific effects upon adipose tissue development. Flint DJ, Gardner MJ.

(4) Hum Reprod. 1997 Oct;12 Suppl 1:21-5. Hormonal control of regional fat distribution.Bjorntorp P.

(5) Horm Res. 2000;53 Suppl 1:87-97. Growth hormone and adipocyte function in obesity Nam SY, Marcus C.

(6) Pediatr Res 1996 Sep;40(3):450-6 Mitogenic and antiadipogenic properties of human growth hormone in differentiating human adipocyte precursor cells in primary culture. Wabitsch M, Braun S, Hauner H, Heinze E, Ilondo MM, Shymko R, De Meyts P, Teller WM

(7) Endocrinology. 2003 Mar;144(3):967-74. Interrelationship between the novel peptide ghrelin and somatostatin/growth hormone-releasing hormone in regulation of pulsatile growth hormone secretion. Tannenbaum GS, Epelbaum J, Bowers CY.

(8) Am J Physiol Endocrinol Metab. 2003 Jul;285(1):E163-E170. Epub 2003 Apr 01. Pulsatile and nocturnal growth hormone secretions in men do not require periodic declines of somatostatin. Dimaraki EV, Jaffe CA, Bowers CY, Marbach P, Barkan AL.

(9) Pombo M, Pombo CM, Astorga R, Cordido F, Popovic V, Garcia-Mayor RV, Dieguez C, Casanueva FF. Regulation of growth hormone secretion by signals produced by the adipose tissue. J Endocrinol Invest 22(5 Suppl):22-6 1999

(10) Endocrinology. 1998 Dec;139(12):4811-9. Hypothalamic mediated action of free fatty acid on growth hormone secretion in sheep. Briard N, Rico-Gomez M, Guillaume V, Sauze N, Vuaroqueaux V, Dadoun F, Le Bouc Y, Oliver C, Dutour A.

(11) Med Sci Sports Exerc. 1995 Jul;27(7):1057-62. Physiological and performance responses to nicotinic-acid ingestion during exercise. Murray R, Bartoli WP, Eddy DE, Horn MK

(12) J Clin Endocrinol Metab. 1988 Mar;66(3):489-94. Enhanced growth hormone (GH) responsiveness to GH-releasing hormone after dietary manipulation in obese and nonobese subjects. Kelijman M, Frohman LA.

(13) Am J Physiol. 1999 Nov;277(5 Pt 1):E824-9. Influence of obesity and body fat distribution on growth hormone kinetics in humans. Langendonk JG, Meinders AE, Burggraaf J, Frolich M, Roelen CA, Schoemaker RC, Cohen AF, Pijl H.

(14) J Clin Endocrinol Metab. 1997 Jul;82(7):2239-43. Evidence for an inhibitory effect of physiological levels of insulin on the growth hormone (GH) response to GH-releasing hormone in healthy subjects. Lanzi R, Manzoni MF, Andreotti AC, Malighetti ME, Bianchi E, Sereni LP, Caumo A, Luzi L, Pontiroli AE.

(15) Metabolism 1999 Sep;48(9):1152-6 Elevated insulin levels contribute to the reduced growth hormone (GH) response to GH-releasing hormone in obese subjects. Lanzi R, Luzi L, Caumo A, Andreotti AC, Manzoni MF, Malighetti ME, Sereni LP, Pontiroli AE.

(16) Am J Physiol Endocrinol Metab. 2003 Feb;284(2):E313-6. The influence of insulin on circulating ghrelin. Flanagan DE, Evans ML, Monsod TP, Rife F, Heptulla RA, Tamborlane WV, Sherwin RS.

(17) Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11381-6. Insulin and insulin-like growth factor-I acutely inhibit surface translocation of growth hormone receptors in osteoblasts: a novel mechanism of growth hormone receptor regulation. Leung KC, Waters MJ, Markus I, Baumbach WR, Ho KK.

(18) Obes Res. 2003 Feb;11(2):170-5. Effects of growth hormone administration in human obesity. Shadid S, Jensen MD.

(19) J Clin Endocrinol Metab. 2002 Jul;87(7):3105-9. Short-term treatment with low doses of recombinant human GH stimulates lipolysis in visceral obese men. Lucidi P, Parlanti N, Piccioni F, Santeusanio F, De Feo P

(20) Int J Obes Relat Metab Disord. 2001 Aug;25(8):1101-7. Low-dose growth hormone treatment combined with diet restriction decreases insulin resistance by reducing visceral fat and increasing muscle mass in obese type 2 diabetic patients. Nam SY, Kim KR, Cha BS, Song YD, Lim SK, Lee HC, Huh KB.

(21) J Clin Endocrinol Metab. 2003 Apr;88(4):1455-63. Growth hormone replacement therapy induces insulin resistance by activating the glucose-fatty acid cycle. Bramnert M, Segerlantz M, Laurila E, Daugaard JR, Manhem P, Groop L.

(22) J Clin Endocrinol Metab. 1997 Dec;82(12):4208-13. Stimulation of mitochondrial fatty acid oxidation by growth hormone in human fibroblasts. Leung KC, Ho KK.

(23) Diabetes. 2001 Jan;50(1):96-104. The protein-retaining effects of growth hormone during fasting involve inhibition of muscle-protein breakdown. Norrelund H, Nair KS, Jorgensen JO, Christiansen JS, Moller N

 

[Whacked]

JA: You might enjoy this article. Check it out.

http://www.mesomorphosis.com/articles/haycock/ephedrine-and-beta-adrenergic-receptors.htm

(Portion of the article----discussing EPHEDRINE for beta-3 stimulation): Another explanation of its increased efficacy after chronic treatment is it’s interaction with the beta-3 receptor. Although the exact structure and function of this receptor is still being explored, it is almost certain that at least 40% of ephedrine’s actions are due to it’s effect on beta-3 receptors.6 A study done to explore this used a beta-1 and beta-2 antagonist called nadolol. Nadolol was administered concomitantly with ephedrine to healthy volunteers. Nadolol completely inhibited changes in heart rate and plasma glucose due to it’s blockade of beta-1 and beta-2 receptors. However, the thermogenic effect of ephedrine was still at about 43%. This means that at least 40% of ephedrine’s thermogenic effects are due to beta-3 activation. This alone does not explain ephedrine’s effects after long term use. What does explain this is the desensitization properties of the beta-3 receptor. Beta-3 receptors lack most of the structural properties that are responsible for beta-2 receptor desensitization.7 So even after ephedrine fails to have significant effects on the beta-2 receptor, it would potentially continue to stimulate adenylate cyclase activity by virtue of its effect on the beta-3 receptor.

 

[majutsu]

I wanted to elaborate a little on our last exchange JA. I know you are all excited about the fat-burning mechanism of GH, and that is good, but of little interest to me. Professionally, the anabolic activity activity of GH has been assumed for the last 15 years, and lately has been called into serious question. Medically, the only common use of GH in non-deficiencies would be for its presumed anabolic activity. Cosmetic use of GH is not standard medical practice. Furthermore, personally, I like powerlifting, and bodybuilding sort of as a corollary to that, but only to the extent that I build lean mass. As you pointed out, there are many cheaper, equally effective options for fat loss for the bodybuilder. In general, the serious bodybuilder has little interest in practices marginally effective at money-bilking weight-loss clinics. So, proving that GH is not anabolic would pretty much mean that no sensical EF member would be using it. You skipped right over the idea that GH is not anabolic, but it's much more important that that. GH DOES NOT BUILD MUSCLE OR INCREASE PROTEIN SYNTHESIS AT ALL IN HEALTHY BODYBUILDERS.

It is so important that I am going to go over the studies. Some of them, like the Yarasheski studies, you already mentioned, but I want to put them all together for the proof/argument.

First is a review of GH's anabolic properties in the literature.

J Endocrinol Invest. 1999;22(5 Suppl):106-9.

Growth hormone and body composition in athletes.

Frisch H.

Department of Pediatrics, University of Vienna, Austria.
[email protected]

The anabolic properties of growth hormone (GH) have been investigated
extensively. The effects of GH on normal, hypertrophied and atrophied muscles
have been studied previously in animal experiments that demonstrated an increase
in muscle weight and size, but no comparable increase in performance or tension.
In adults with GH deficiency, the changes in body composition can be corrected
by GH treatment; lean body mass and strength increase within a few months. In
children with GH deficiency, Turner's syndrome or intrauterine growth
retardation, an increase in muscle tissue is seen after treatment with GH. In
acromegalics with long-standing GH hypersecretion, the muscle volume is
increased, but muscle strength and performance are not improved. These
observations gave rise to the interest shown by healthy subjects and athletes in
using GH to increase their muscle mass and strength. The improvements in muscle
strength obtained by resistance exercise training in healthy older men or young
men were not enhanced by additional administration of GH. The larger increases
in fat-free mass observed in the GH-treated groups were obviously not due to
accretion of contractile protein, but rather to fluid retention or accumulation
of connective tissue. In experienced weightlifters, the incorporation of amino
acids into skeletal muscle protein was not increased and the rate of whole body
protein breakdown was not decreased by short-term administration of GH. The
results of a study in power athletes confirm the results of these
investigations. The study used GH treatment in power athletes compared with a
placebo-control group, and the results indicated no increase in maximal strength
during concentric contraction of the biceps and quadriceps muscles, although
levels of insulin-like growth factor-I were doubled. In highly trained power
athletes with low fat mass and high lean body mass, no additional effect of GH
treatment on strength is to be expected.

Publication Types:
Review
Review, Tutorial

PMID: 10442579 [PubMed - indexed for MEDLINE]


Next comes the clinical slaying of GH as an anabolic. It didn't increase protein synthesis in athletes, regular young men, or even regular old men


J Appl Physiol. 1993 Jun;74(6):3073-6.

Short-term growth hormone treatment does not increase muscle protein synthesis
in experienced weight lifters.

Yarasheski KE, Zachweija JJ, Angelopoulos TJ, Bier DM.

Metabolism Division, Washington University School of Medicine, St. Louis,
Missouri 63110.

The purpose of this study was to determine whether recombinant human growth
hormone (GH) administration enhances muscle protein anabolism in experienced
weight lifters. The fractional rate of skeletal muscle protein synthesis and the
whole body rate of protein breakdown were determined during a constant
intravenous infusion of [13C]leucine in 7 young (23 +/- 2 yr; 86.2 +/- 4.6 kg)
healthy experienced male weight lifters before and at the end of 14 days of
subcutaneous GH administration (40 microgram.kg-1 x day-1). GH administration
increased fasting serum insulin-like growth factor-I (from 224 +/- 20 to 589 +/-
80 ng/ml, P = 0.002) but did not increase the fractional rate of muscle protein
synthesis (from 0.034 +/- 0.004 to 0.034 +/- 0.002%/h) or reduce the rate of
whole body protein breakdown (from 103 +/- 4 to 108 +/- 5 mumol.kg-1 x h-1).
These findings suggest that short-term GH treatment does not increase the rate
of muscle protein synthesis or reduce the rate of whole body protein breakdown,
metabolic alterations that would promote muscle protein anabolism in experienced
weight lifters attempting to further increase muscle mass.

PMID: 8366011 [PubMed - indexed for MEDLINE]


Am J Physiol. 1992 Mar;262(3 Pt 1):E261-7.

Effect of growth hormone and resistance exercise on muscle growth in young men.

Yarasheski KE, Campbell JA, Smith K, Rennie MJ, Holloszy JO, Bier DM.

Department of Medicine, Washington University School of Medicine, St. Louis,
Missouri 63110.

The purpose of this study was to determine whether growth hormone (GH)
administration enhances the muscle anabolism associated with heavy-resistance
exercise. Sixteen men (21-34 yr) were assigned randomly to a resistance training
plus GH group (n = 7) or to a resistance training plus placebo group (n = 9).
For 12 wk, both groups trained all major muscle groups in an identical fashion
while receiving 40 micrograms recombinant human GH.kg-1.day-1 or placebo.
Fat-free mass (FFM) and total body water increased (P less than 0.05) in both
groups but more (P less than 0.01) in the GH recipients. Whole body protein
synthesis rate increased more (P less than 0.03), and whole body protein balance
was greater (P = 0.01) in the GH-treated group, but quadriceps muscle protein
synthesis rate, torso and limb circumferences, and muscle strength did not
increase more in the GH-treated group. In the young men studied, resistance
exercise with or without GH resulted in similar increments in muscle size,
strength, and muscle protein synthesis, indicating that 1) the larger increase
in FFM with GH treatment was probably due to an increase in lean tissue other
than skeletal muscle and 2) resistance training supplemented with GH did not
further enhance muscle anabolism and function.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 1550219 [PubMed - indexed for MEDLINE]


Am J Physiol. 1995 Feb;268(2 Pt 1):E268-76.

Effect of growth hormone and resistance exercise on muscle growth and strength
in older men.

Yarasheski KE, Zachwieja JJ, Campbell JA, Bier DM.

Metabolism Division, Washington University School of Medicine, St. Louis,
Missouri 63110.

The purpose of this study was to determine whether growth hormone (GH)
administration enhances the muscle protein anabolism associated with
heavy-resistance exercise training in older men. Twenty-three healthy, sedentary
men (67 +/- 1 yr) with low serum insulin-like growth factor I levels followed a
16-wk progressive resistance exercise program (75-90% max strength, 4 days/wk)
after random assignment to either a GH (12.5-24 micrograms.kg-1.day-1; n = 8) or
placebo (n = 15) group. Fat-free mass (FFM) and total body water increased more
in the GH group. Whole body protein synthesis and breakdown rates increased in
the GH group after treatment. However, increments in vastus lateralis muscle
protein synthesis rate, urinary creatinine excretion, and training-specific
isotonic and isokinetic muscle strength were similar in both groups, while 24-h
urinary 3-methylhistidine excretion was unchanged after treatment. These
observations suggest that resistance exercise training improved muscle strength
and anabolism in older men, but these improvements were not enhanced when
exercise was combined with daily GH administration. The greater increase in FFM
with GH treatment may have been due to an increase in noncontractile protein and
fluid retention.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 7864103 [PubMed - indexed for MEDLINE]


In short, GH administration scientifically, in placebo-controlled studies, doesn't increase protein synthesis or build muscle mass at all. The gain is all due to water and connective tissue

Why is it that muscular contractions (resistance training) cause spikes in GH and localized IGF, but administration of GH does not affect protein synthesis? GH and IGF also have localized muscle action in an autocrine/paracrine fashion that are important for muscle growth.

Local cytokines from contractile micro-injury interact with GH and IGF as well as other factors to mount a protective response (growth) to the overload stress (weight). Dumping GH into the system is useless, as the system reacts to SPIKES not absolute blood levels of GH. Note that IGF injections suffer from the same lack of efficacy for the same reasons.

This basic science study shows GH does act locally for protein synthesis and muscle growth. In this study, GH increases protein synthesis and inhibits the proteolytic actiion of insulin.

Diabetes. 1992 Apr;41(4):424-9.

Growth hormone stimulates skeletal muscle protein synthesis and antagonizes
insulin's antiproteolytic action in humans.

Fryburg DA, Louard RJ, Gerow KE, Gelfand RA, Barrett EJ.

Department of Internal Medicine, Yale University School of Medicine, New Haven,
Connecticut.

We examined the effects of a combined, local intra-arterial infusion of growth
hormone (GH) and insulin on forearm glucose and protein metabolism in seven
normal adults. GH was infused into the brachial artery for 6 h with a dose that,
in a previous study, stimulated muscle protein synthesis (phenylalanine Rd)
without affecting systemic GH, insulin, or insulinlike growth factor I
concentrations. For the last 3 h of the GH infusion, insulin was coinfused with
a dose that, in the absence of infused GH, suppressed forearm muscle proteolysis
by 30-40% without affecting systemic insulin levels. Measurements of forearm
glucose, amino acid balance, and [3H]phenylalanine and [14C]leucine kinetics
were made at 3 and 6 h of the infusion. Glucose uptake by forearm tissues in
response to GH and insulin did not change significantly between 3 and 6 h. By 6
h, the combined infusion of GH and insulin promoted a significantly more
positive net balance of phenylalanine, leucine, isoleucine, and valine (all P
less than 0.05). The change in net phenylalanine balance was due to a
significant increase in phenylalanine Rd (51%, P less than 0.05) with no
observable change in phenylalanine Ra. For leucine, a stimulation of leucine Rd
(50%, P less than 0.05) also accounted for the change in leucine net balance,
with no suppression of leucine Ra. The stimulation of Rd, in the absence of an
observed effect on Ra, suggests that GH blunts the action of insulin to suppress
proteolysis in addition to blunting insulin's action on Rd.

PMID: 1607069 [PubMed - indexed for MEDLINE]

Now, compares this lack of an effect of GH to the clear and obvious effect of oxandrolone or testosterone upon protein synthesis and muscle mass. With real anabolics, there is no doubt. Note that IGF doesn't increase with this. Also notice the many favorable properties of oxandrolone. This is why it is one of my favorites (alone with nandrolone and testosterone) for clinical anabolic use.


J Clin Endocrinol Metab. 1999 Aug;84(8):2705-11.

Short-term oxandrolone administration stimulates net muscle protein synthesis in
young men.

Sheffield-Moore M, Urban RJ, Wolf SE, Jiang J, Catlin DH, Herndon DN, Wolfe RR,
Ferrando AA.

Department of Surgery, University of Texas Medical Branch, and Shriners Burn
Hospital for Children, Galveston 77550, USA. [email protected]

Short term administration of testosterone stimulates net protein synthesis in
healthy men. We investigated whether oxandrolone [Oxandrin (OX)], a synthetic
analog of testosterone, would improve net muscle protein synthesis and transport
of amino acids across the leg. Six healthy men [22+/-1 (+/-SE) yr] were studied
in the postabsorptive state before and after 5 days of oral OX (15 mg/day).
Muscle protein synthesis and breakdown were determined by a three-compartment
model using stable isotopic data obtained from femoral arterio-venous sampling
and muscle biopsy. The precursor-product method was used to determine muscle
protein fractional synthetic rates. Fractional breakdown rates were also
directly calculated. Total messenger ribonucleic acid (mRNA) concentrations of
skeletal muscle insulin-like growth factor I and androgen receptor (AR) were
determined using RT-PCR. Model-derived muscle protein synthesis increased from
53.5+/-3 to 68.3+/-5 (mean+/-SE) nmol/min.100 mL/leg (P < 0.05), whereas protein
breakdown was unchanged. Inward transport of amino acids remained unchanged with
OX, whereas outward transport decreased (P < 0.05). The fractional synthetic
rate increased 44% (P < 0.05) after OX administration, with no change in
fractional breakdown rate. Therefore, the net balance between synthesis and
breakdown became more positive with both methodologies (P < 0.05) and was not
different from zero. Further, RT-PCR showed that OX administration significantly
increased mRNA concentrations of skeletal muscle AR without changing
insulin-like growth factor I mRNA concentrations. We conclude that short term OX
administration stimulated an increase in skeletal muscle protein synthesis and
improved intracellular reutilization of amino acids. The mechanism for this
stimulation may be related to an OX-induced increase in AR expression in
skeletal muscle.

PMID: 10443664 [PubMed - indexed for MEDLINE]


J Appl Physiol. 1989 Jan;66(1):498-503.

Effect of testosterone on muscle mass and muscle protein synthesis.

Griggs RC, Kingston W, Jozefowicz RF, Herr BE, Forbes G, Halliday D.

Department of Neurology, University of Rochester School of Medicine and
Dentistry, New York 14642.

We have studied the effect of a pharmacological dose of testosterone enanthate
(3 mg.kg-1.wk-1 for 12 wk) on muscle mass and total-body potassium and on
whole-body and muscle protein synthesis in normal male subjects. Muscle mass
estimated by creatinine excretion increased in all nine subjects (20% mean
increase, P less than 0.02); total body potassium mass estimated by 40K counting
increased in all subjects (12% mean increase, P less than 0.0001). In four
subjects, a primed continuous infusion protocol with L-[1-13C]leucine was used
to determine whole-body leucine flux and oxidation. Whole-body protein synthesis
was estimated from nonoxidative flux. Muscle protein synthesis rate was
determined by measuring [13C]leucine incorporation into muscle samples obtained
by needle biopsy. Testosterone increased muscle protein synthesis in all
subjects (27% mean increase, P less than 0.05). Leucine oxidation decreased
slightly (17% mean decrease, P less than 0.01), but whole-body protein synthesis
did not change significantly. Muscle morphometry showed no significant increase
in muscle fiber diameter. These studies suggest that testosterone increases
muscle mass by increasing muscle protein synthesis.

PMID: 2917954 [PubMed - indexed for MEDLINE]

In short, GH IS NOT ANABOLIC AT ALL. IT WILL NOT SIGNIFICANTLY INCREASE LEAN MUSCLE MASS OR PROTEIN SYNTHESIS. USING IT FOR THIS PURPOSE IS A SHEER WASTE OF MONEY AND TIME.

 

[Whacked]

I respectfully disagree Majutsu.

From all that I have read on the subject, HGH (somatotropin) WILL in fact cause increase muscle mass; albeit, without very impressive/significant numbers to report. Without AS, this noticeable "muscle mass increases" will be subtle and NOT so pronounced.

My spin: Using it for increased lean muscle mass would be rather disappointing and ignorant IMO as it is extremely expensive and not nearly as effective as gear. But to deny or discount it's increased production of IGF-1 (hence signaling muscle growth) would be incorrect.

Growth hormone regulation of the type 2 IGF receptor in regenerating skeletal muscle of rats

S P Kirk, M A Whittle, J M Oldham, P M Dobbie and J J Bass

Growth and Meat Science Group, AgResearch, Ruakura Agricultural Research Centre, Hamilton, New Zealand
(Requests for offprints should be addressed to SP Kirk, Growth and Meat Science Group, AgResearch, Ruakura Agricultural Research Centre, Private Bag 3123, Hamilton, New Zealand)

--------------------------------------------------------------------------------

Abstract
Growth hormone enhances skeletal muscle growth, and IGF-II peptide is highly expressed during regeneration. We have therefore investigated the effect of growth hormone (GH) administration on IGF-II binding and expression in regenerating rat skeletal muscle using the techniques of receptor autoradiography and in situ hybridisation. Notexin, a myotoxin, was injected into the right M. biceps femoris (day 0), causing affected fibres to undergo necrosis followed by rapid regeneration. Animals were administered either GH (200ug/100g body weight) or saline vehicle daily. Contralateral muscles were used as regeneration controls. GH administration during regeneration resulted in significant increases in body weight, and damaged and undamaged muscle weights (P<0.001). IGF-II expression, which was examined in regenerating fibres, survivor fibres, and undamaged fibres, varied according to tissue type (P<0.001). Specifically, IGF-II expression in regenerating fibres was elevated relative to control and survivor fibres after day 3 (P<0.05), with a peak on day 9 (P<0.001). GH did not affect IGF-II message levels. (125) I-IGF-II binding in regenerating muscle was examined in the same fibre types as well as in connective tissue. (125) I-IGF-II binding in regenerating fibres was higher (P<0.001) than in other tissue types on day 5. GH administration increased (125) I-IGF-II binding in all damaged muscle tissues on day 5 (P<0.001, regenerating fibres; P<0.01, others). We believe this shows for the first time an effect of GH on the Type 2 IGF receptor in regenerating skeletal muscle.

Journal of Endocrinology

 

[majutsu]

say what you will whacked, you can reason and analyze all you wish, in actual human beings at commonly used dosages (e.g. 4u ed) for up to 3 months, there is no effect in over 5 studies (of which 3 were given) upon lean body mass by any measure including MRI. Furthermore, there is no effect upon protein synthesis. You do believe in duplicated human studies, don't you? Older studies found limited fat-free mass gain, (perhaps this is what you refer too in saying "subtle" gain) but did not take time to distinguish whether this was muscle (what we want) or cartilage and fluid (which it was). You seem to be addicted to posts by self-appointed gurus on other forums, and old biochem studies in rats. This is not nearly as decisive as the simple clinical human trials to which GH is currently being submitted. Unfortunately, our biochemical reasonings and fantasies of 5 years ago do not always pan out in reality. Exogenous GH administration is not anabolic in normal humans.

Next, I may argue that fat loss with testosterone could be seen as more impressive than that of GH . . . But I am still waiting for the fat-loss kings to talk about how GH switches the body to a free-fatty acid metabolism.

 

[Whacked]

So what exactly does HGH (and subsequent increased Igf-1 production) DO in your opinion? You may be the only one in the entire world right now believing that Somatotropin is essentially useless (this specualtion is derived from all your recent GH posts). Do you really believe that all the freakish bb'ers out there today are like that ONLY b/c they increased AS intake compared to that of yester-year? GH (IGF-1 more directly) is the answer! Inarguably! Or do you believe that all of a sudden evolution kicked into high gear and produced insane amounts of genetic anomalies?

And by the way......my 1st sentence (above post) was "I respectfully disagree Majutsu". How about a little reciprocation?

Also: Self-proclaimed guru's or not.......these people bring incredible valuable information to the table.
Guys such as Nandi/Macro/Hhajdo/Ulter/BigCat research the shit out of things.............like 'em or not---these "guru's" bring a wealth of knowledge to the table NOT only from mere speculatory reasoning but back many of there claims with research. That's certainly better than nothing! Someone has to reason thru all these designer steroids, HGH, IGF-1 products seen all over the place these days!