IGF-1 A Messenger Of Testosterone?
For the adapt to environmental demands chemical signals create changes to adapt to the needs of the individual. An example of this would be how the body secretes insulin during a meal as blood sugar rises sending the nutrients into the active tissue. To accumulate muscle tissue hormones increase contractile proteins as well as increase cytoskeletal structure as a result this facilitates greater muscle mass and strength. The body’s most familiar anabolic hormone is testosterone. Testosterone is produced in the in the testes in a self regulated fashion and circulates through the body to target androgen receptors. When Testosterone attaches to a membrane bound androgen receptor it generates an immediate response known as a non genomic response. Cytosolic androgen receptors attach to the testosterone that enters the cell and cofactors aid in altering specific genes in the DNA of the nucleus. Responses that follow the stimulation of genes in the DNA of the nucleus are known as genomic responses, and may take from as short as a few hours to as long as a few weeks to become present since they depend upon the creation of new proteins affecting cell activity or tissue structure. Considering the changes that occur during puberty facial and pubic hair, genital changes, voice deepening. These changes occur over a period of two to five years. Testosterone is not the only hormone that affects muscle. Among the multitude of others one is commonly known “GH” Growth Hormone. In Replacement doses, GH does not have a direct anabolic effect that results in noticeable increases in muscle size and strength instead GH Related anabolic effects are the result of a secondary messenger called igf-1. The term “secondary messenger” means that once a tissue or cell gets influenced by a hormone, it develops another hormone to get the desired effect. GH is secreted by the pituitary gland in the brain and targets nearly every tissue type in the body[fat,heart,bone, skeletal muscle, intestines ect.] In some tissues, GH causes a direct response, such as promoting a breakdown of stored fat in fat cells. Optimal health requires GH’s direct effects and indirect effects through igf-1. A major target for gh is the liver. GH stimulation induces the production of igf-1. A major target for GH is the liver GH stimulation induces the production of igf-1 by hepatocytes [liver cells], accounting for over two-thirds of circulating igf-1. The remainder of circulating igf-1 comes from skeletal muscle. Most circulating igf-1 is bound to carrier proteins [75 percent to igfbp-3, 20 percent to other proteins]. Circulating GH and Igf-1 travel to other tissues, generating a tissue specific response [increased bone mass and density, fat loss from fat cells]. As mentioned, skeletal muscle is the source of a considerable amount of igf-1 not only does this help keep the body in an anabolic state as a whole, but its vital for building mass and strength. In fact, most muscle derived IGF-1 acts locally or near the site it was developed. Bodybuilders have seen that GH does not aid in increasing muscle mass unless it is utilized in doses so high it will cause undesirable side effects [facial bone growth, lengthening of extremities, edema ect]. Yet when insulin and IGF-1 were added to GH a new era of bodybuilding was launched. Ask the Bodybuilder who has practical experience with both GH and IGF-1 and he will tell you there is no comparison in regard to mass building at tolerable doses. Unfortunately/fortunately igf-1 is expensive, difficult to source, and has many poorly understood risks. Elevated igf-1 is associated with a elevated risk for certain cancers and more aggressive tumors. There is another distinct difference between the the igf-1 produced by the liver and igf-1 generated in muscle tissue. Liver based igf-1 is also called igf-1ea, and is formed from a large precursor protein by cutting out two very specific molecular regions. This structure allows liver based igf-1 to have a long half life, partly by promoting binding carrier proteins. Muscle based igf-1 is also formed from the same large precursor protein, but different sections are cut out forming three types called igf-1ea, igf-1eb and igf-1ec [or mgf] respectively. MGF or mechano-growth factor is a type of igf-1 that appears to be unique to muscle. it does not bind to the typical igf-binding proteins, limiting its effectiveness to the muscle, nerves and connective tissue near its site of production. Muscle based igf-1ea and MGF production can be stimulated by the working or injured muscle to promote igf-1 production within the muscle cells. Thus local igf-1 production is a regenerative function in the muscle. If a progressive challenge is present in the muscle over time, this will result in a larger and stronger muscle. An interesting difference exists between igf-1ea and mgf. In muscle tissue mgf increases the proliferation in of satellite cells, which act as muscle cell precursors. Satellite cells sit quietly beside mature muscle cells dormant until they are turned on by hormones then they adhere to the mature muscle and bind combining their DNA into the nucleus pool of the muscle cells. Skeletal muscle is unlike most other cells in that it contains many nuclei most cells only have one nucleus. Increasing the nucleus number is crucial to muscle cell growth, as the maximum size is limited to a factor of the nucleus content, the more nuclei the greater of an increase in tissue size can occur. Simply adding a nucleus to a muscle cell doesn’t increase muscle size or strength. The other form of igf-1 formed in working skeletal muscle tissue promotes maturation and development. This can occur even if a new nucleus is not added, but it is limited by the nuclear:cytoplasmic ratio. Clearly for maximal muscle size and strength, a coordinated effect is necessary. Certain people cannot generate mgf but do produce igf-1ea, such as those suffering from muscular dystrophy. Even when treated with GH or Igf-1, these individuals lose muscle tissue, being replaced by fatty connective tissue. Individuals who use supraphysiological doses of GH and Igf-1 see tremendous tissue growth, but likewise elderly people dont see this effect when suffering from muscle loss. GH in the absence of exercise [load-bearing on the muscle] will generate a large increase in igf-1ea in muscle cells but the effect on MGF is modest and delayed. Exercise alone will increase igf-1ea but more vigorously stimulates MGF. When GH and exercise are combined, igf-1ea was increased more than by exercise alone but less then gh alone MGF was markedly higher this suggest that even moderate exercise is more effective then utilizing GH in a sedentary state, but when the two are combined the effects are truly synergistic and produce massive results.