GH and IGF-1 on Satellite Cell Expression

When 1+1=3
When you combine growth hormone with a powerful androgen, you get some serious muscle building, because GH increases satellite cell proliferation, gets you lean and increases IGF-1 production. IGF-1 builds muscle and increases satellite cell expression while burning fat. This is what makes growth hormone worth the 300-400 dollars per week the professionals spend on a cycle, even before IGF-1 was available. Growth hormone burns fat, but also greatly increases IGF-1 levels, which if you are in the circle of knowledge is VERY important, since IGF-1 is a natural anabolic.

IGF-1 and GH can be stimulated by the body, meaning that your natural levels can be increased, which gives you the ability to get most of the same results as a pro bodybuilder without the expense or risk. GH secretagogues (things that increase your natural production or secretion) are on the market and they should at least include things like ArgininePryoglutamate, Ornithine, Astragulus, and L-Dopa. These are the most potent Growth Hormone secretagogues on the market and can sky rocket your GH levels, allowing you to build slabs of muscle. GH is pretty easy to increase with the use of secretagogues, but IGF-1 is very tough to boost naturally. There is only one ingredient I know that increases IGF-1 naturally. This is in products like Formadrol Extremeä pictured above, and the ingredient is Daidzein, which is the only known naturally occurring IGF-1 secretagogue. So how does GH increase satellite expression? Again, let’s look at the literature.

GH and IGF-1 on Satellite Cell Expression

Effects of growth hormone on skeletal muscle. I. Studies on normal adult rats.
Ullman M, Oldfors A.

Department of Pathology, Gothenburg University, Sweden.

A study was made on the effects of recombinant human growth hormone (rhGH) on fast and slow skeletal muscle in normal adult female rats. Daily injections of 4 IE of rhGH over 36 days resulted in increased levels of insulin-like growth factor I in serum and increased body weight. Morphometric analysis of the muscle fibres of the extensor digitorum longus (EDL) and soleus muscles revealed a significant increase in diameter of both type 1 and type 2 fibres in both muscles. The DNA: protein ratio and the number of satellite cells:muscle fibre in cross-sections was increased in the GH-treated rats in relation to controls. The results show that rhGH has pronounced effects on both cell proliferation and muscle fibre growth in skeletal muscle of normal adults rats.

IGF-1 induces human myotube hypertrophy by increasing cell recruitment.Jacquemin V, Furling D, Bigot A, Butler-Browne GS, Mouly V.

CNRS UMR 7000 Cytosquelette et Developpement, Paris, France.

Insulin-like growth factor-1 (IGF-1) has been shown in rodents (i) in vivo to induce muscle fiber hypertrophy and to prevent muscle mass decline with age and (ii) in vitro to enhance the proliferative life span of myoblasts and to induce myotube hypertrophy. In this study, performed on human primary cultures, we have shown that IGF-1 has very little effect on the proliferative life span of human myoblasts but does delay replicative senescence. IGF-1 also induces hypertrophy of human myotubes in vitro, as characterized by an increase in the mean number of nuclei per myotube, an increase in the fusion index, and an increase in myosin heavy chain (MyHC) content. In addition, muscle hypertrophy can be triggered in the absence of proliferation by recruiting more mononucleated cells. We propose that IGF-1-induced hypertrophy can involve the recruitment of reserve cells in human skeletal muscle.

Insulin-like growth factor 1 and muscle growth: implication for satellite cell proliferation.Machida S, Booth FW.

Department of Biomedical Sciences, University of Missouri-Columbia, E102 Veterinary Medical Building, 1600 East Rollins Road, Columbia, MO 65211, USA.

Insulin-like growth factor 1 (IGF-1) has been shown to rescue the aging-related or inactivity-induced loss of muscle mass through the activation of satellite cells. However, the signalling pathways and the mechanism by which IGF-1 affects satellite cells have not been not completely identified. The purpose of the present review is to provide current understanding of the cellular and molecular events underlying IGF-1 induced proliferation of satellite cells.

Expression and splicing of the insulin-like growth factor gene in rodent muscle is associated with muscle satellite (stem) cell activation following local tissue damage.Hill M, Goldspink G.

Basic Medical Sciences and Department of Surgery, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK.

Muscle satellite cells are mononuclear cells that remain in a quiescent state until activated when they proliferate and fuse with muscle fibres to donate nuclei, a process necessary for post-embryonic growth, hypertrophy and tissue repair in this post-mitotic tissue. These processes have been associated with expression of the insulin-like growth factor (IGF-I) gene that can undergo alternative splicing to generate different gene products with varying functions. To gain insight into the cellular mechanisms involved in local tissue repair, the time courses of expression of two IGF-I splice variants produced in muscle were determined together with marker genes for satellite cell activation following local muscle damage. Using real-time RT-PCR with specific primers, the mRNA transcripts in rat tibialis anterior muscles were measured at different time intervals following either mechanical damage imposed by electrical stimulation of the stretched muscle or damage caused by injection with bupivacaine. It was found that the autocrine splice variant mechano growth factor (MGF) was rapidly expressed and then declined within a few days following both types of damage. Systemic IGF-IEa was more slowly upregulated and its increase was commensurate with the rate of decline in MGF expression. Satellite cell activation as measured by M-cadherin and one of the muscle regulatory factors MyoD and the sequence of expression suggests that the initial pulse of MGF is responsible for satellite cell activation, as the systemic IGF-IEa mRNA expression peaks after the expression of these markers, including M-cadherin protein. Later splicing of the IGF-I gene away from MGF but towards IGF-IEa seems physiologically appropriate as IGF-IEa is the main source of mature IGF-I for upregulation of protein synthesis required to complete the repair.

GH on Muscle:

Growth hormone / insulin-like growth factor-1 axis during puberty.
Christoforidis A, Maniadaki I, Stanhope R.

Department of Endocrinology, Great Ormond Street Hospital and the Middlesex Hospital (UCLH), London, UK.

Puberty is a dynamic, transitional period of life which is characterized by the acquisition of secondary sexual characteristics leading to the development of fertility. Puberty is accompanied by sexually dimorphic changes in linear growth, body proportions and body composition. The pubertal growth spurt is influenced by a number of factors such as hormones, nutrition, physical activity and general health, acting mostly in concert in order to modify a genetic potential for growth. Growth hormone (GH) is traditionally considered to be the main regulator of growth. During puberty, elevated sex steroid concentrations (especially oestrogens) stimulate GH production, leading to an activation of the whole GH/Insulinlike growth factor-1 (IGF-1) axis. This activation is mostly characterized by an increase in the amplitude of GH pulses rather than an increase in frequency or in duration. Interactions between GH and sex steroids (especially androgens) express an anabolic effect on muscle mass, bone mineralization and body proportion which constitutes the male and the female adult body composition.

Intact insulin and insulin-like growth factor-I receptor signaling is required for growth hormone effects on skeletal muscle growth and function in vivo.
Kim H, Barton E, Muja N, Yakar S, Pennisi P, Leroith D.

Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 8D12, Bethesda, Maryland 20892-1758, USA.

GH and IGF-I are potent regulators of muscle growth and function. Although IGF-I is known to mediate many of the effects of GH, it is not yet clear whether all effects of GH are completely dependent on the IGF-I system. To evaluate the biological effects of the GH/IGF-I axis on muscle growth, we administrated recombinant human GH to mice, which lack IGF-I function specifically in skeletal muscle, due to the overexpression of a dominant-negative IGF-I receptor in this tissue (MKR mice). GH treatment significantly increased the levels of hepatic IGF-I mRNA and serum IGF-I levels in both wild-type (WT) and MKR mice. These GH-induced effects were paralleled by increases in body weight and in the weights of most GH-responsive organs in both groups of mice. Interestingly, unlike WT mice, GH treatment had no effect on skeletal muscle weight in MKR mice. GH treatment failed to reverse the impaired muscle function in MKR mice. Furthermore, MKR mice exhibited no effects of GH on the cross-sectional area of myofibers and the proliferation of satellite cells. Taken together, these data suggest that the in vivo effects of GH on muscle mass and strength are primarily mediated by activation of the IGF-I receptor.

Insulin-like growth factor 1 and muscle growth: implication for satellite cell proliferation.
Machida S, Booth FW.

Department of Biomedical Sciences, University of Missouri-Columbia, E102 Veterinary Medical Building, 1600 East Rollins Road, Columbia, MO 65211, USA.

Insulin-like growth factor 1 (IGF-1) has been shown to rescue the aging-related or inactivity-induced loss of muscle mass through the activation of satellite cells. However, the signalling pathways and the mechanism by which IGF-1 affects satellite cells have not been not completely identified. The purpose of the present review is to provide current understanding of the cellular and molecular events underlying IGF-1 induced proliferation of satellite cells.

The effects of growth hormone and/or Testosterone in healthy elderly men: a randomized controlled trial.
Giannoulis MG, Sonksen PH, Umpleby M, Breen L, Pentecost C, Whyte M, McMillan CV, Bradley C, Martin FC.

Department of Diabetes and Endocrinology, GKT School of Medicine, King's College London, St. Thomas' Hospital, London SE1 7EH, UK.

CONTEXT: Declines in GH and testosterone (Te) secretion may contribute to the detrimental aging changes of elderly men. OBJECTIVE: To assess the effects of near-physiological GH with/without Te administration on lean body mass, total body fat, midthigh muscle cross-section area, muscle strength, aerobic capacity, condition-specific quality of life (Age-Related Hormone Deficiency-Dependent Quality of Life questionnaire), and generic health status (36-Item Short-Form Health Survey) of older men. DESIGN, SETTINGS, AND PARTICIPANTS: A 6-month, randomized, double-blind, placebo-controlled trial was performed on 80 healthy, community-dwelling, older men (age, 65-80 yr). INTERVENTIONS: Participants were randomized to receive 1) placebo GH or placebo Te, 2) recombinant human GH (rhGH) and placebo Te (GH), 3) Te and placebo rhGH (Te), or 4) rhGH and Te (GHTe). GH doses were titrated over 8 wk to produce IGF-I levels in the upper half of the age-specific reference range. A fixed dose of Te (5 mg) was given by transdermal patches. RESULTS: Lean body mass increased with GHTe (P = 0.008) and GH (P = 0.004), compared with placebo. Total body fat decreased with GHTe only (P = 0.02). Midthigh muscle (P = 0.006) and aerobic capacity (P < 0.001) increased only after GHTe. Muscle strength changes were variable; one of six measures significantly increased with GHTe. Significant treatment group by time interactions indicated an improved Age-Related Hormone Deficiency-Dependent Quality of Life questionnaire score (P = 0.007) in the GH and GHTe groups. Bodily pain increased with GH alone, as determined by the Short-Form Health Survey (P = 0.003). There were no major adverse effects. CONCLUSION: Coadministration of low dose GH with Te resulted in beneficial changes being observed more often than with either GH or Te alone.

Supraphysiological growth hormone: less fat, more extracellular fluid but uncertain effects on muscles in healthy, active young adults.
Ehrnborg C, Ellegard L, Bosaeus I, Bengtsson BA, Rosen T.

Research Centre for Endocrinology and Metabolism, Department of Internal Medicine, Sahlgrenska University Hospital, S-413 45 Goteborg, Sweden. [email protected] OBJECTIVES: To study the effects on body composition after 1 month's administration of supraphysiological doses of growth hormone (GH) in healthy, active young adults with normal GH-IGF-I axis. SUBJECTS AND METHODS: Thirty healthy, physically active volunteers (15 men and 15 women), mean age 25.9 years (range 18-35), participated in this study, designed as a randomized, double-blind, placebo-controlled, parallel study with three groups (n = 10: five men and five women in each group). The groups comprised the following: placebo (P), GH 0.1 IU/kg/day [0.033 mg/kg/day] (GH 0.1) and GH 0.2 IU/kg/day [0.067 mg/kg/day] (GH 0.2). RESULTS: In the pooled group with active GH treatment (n = 20) the results showed significant increases: IGF-I increased by 134% (baseline vs. after 1 month), body weight by 2.7%, fat free mass by 5.3%, total body water by 6.5% and extracellular water (ECW) by 9.6%. Body fat decreased significantly by 6.6%. No significant change in intracellular water was detected. The observed increase in fat free mass by 5.3% was explained by the ECW increase, indicating limited anabolic effects of the supraphysiological GH doses. Changes were noticeable in both genders, although more prominent in the male subjects. Fluid retention symptoms occurred in the majority of individuals. CONCLUSIONS: This is, to our knowledge, the first placebo-controlled trial to show the effects of supraphysiological GH doses on body composition and IGF-I levels in physically active and healthy individuals of both genders; the results indicate limited anabolic effects of GH with these supraphysiological doses. The role of GH as an effective anabolic-doping agent is questioned.

GH alone is not enough, which is why we stack…
Here is an example of an effective stacking of compatible supplements to achieve a specific objective.

Regulating of growth hormone sensitivity by sex steroids: implications for therapy.
KK, Gibney J, Johannsson G, Wolthers T.
Pituitary Research Unit, Garvan Institute of Medical Research and Department of Endocrinology, St. Vincent's Hospital, Sydney, Australia.

Growth hormone (GH) is an important regulator of body composition, reducing body fat by stimulating fat oxidation and enhancing lean body mass by stimulating protein accretion. The emergence of differences in body composition between the sexes during puberty suggests sex steroids modulate the action of GH. Work from our laboratory have investigated the influence of estrogens and androgens on the metabolic actions of GH in human adults. The liver is an important site of physiological interaction as it is a sex steroid responsive organ and a major target of GH action. Estrogen, when administered orally impairs the GHregulated endocrine and metabolic function of the liver via a first-pass effect. It reduces circulating IGF-I, fat oxidation and protein synthesis, contributing to a loss of lean and a gain of fat mass. These effects occur in normal and in GH-deficient women and are avoided by transdermal administration of physiological doses of estrogen. In contrast, studies in hypopituitary men indicate that testosterone enhances the metabolic effects of GH. Testosterone alone stimulates fat oxidation and protein synthesis, both of which are enhanced by GH. Studies in GH deficiency adults have consistently reported women to be less sensitive to GH than men. In summary, estrogens and androgens exert divergent effects on the action of GH. The results provide an explanation for sexual dimorphism in body composition in adults and the genderrelated response to GH replacement in hypopituitary subjects. In the management of hypopituitarism, estrogens should be administered by the parenteral route in women and testosterone be replaced in men to optimize the benefits of GH replacement.