IGF1 works local?!

[fred9]

Effects of systemic and local administration of recombinant human IGF-I (rhIGF-I) on de novo bone formation in an aged mouse model.Fowlkes JL, Thrailkill KM, Liu L, Wahl EC, Bunn RC, Cockrell GE, Perrien DS, Aronson J, Lumpkin CK Jr.
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. [email protected]

DO was used in an aged mouse model to determine if systemically and/or locally administered rhIGF-I improved osteoblastogenesis and new bone formation. Local and systemic rhIGF-I treatment increased new bone formation. However, only systemic delivery produced measurable concentrations of rhIGF-I in the circulation. INTRODUCTION: Human and rodent research supports a primary role for IGF-I in bone formation. Significant roles for both endocrine and paracrine/autocrine IGF-I have been suggested for normal osteoblastogenesis and bone formation. We have assessed, using a mouse model of distraction osteogenesis (DO), the impact of continuous administration of recombinant human (rh)IGF-I, delivered either locally to the distraction site or absorbed systemically, on bone formation in an aged mouse model. MATERIALS AND METHODS: DO was performed in aged mice (18-month-old C57BL/6 male mice), which were distracted at 0.15 mm daily. At the time of osteotomy, miniosmotic pumps were inserted subcutaneously to (1) deliver vehicle or rhIGF-I subcutaneously for systemic delivery or (2) deliver vehicle or rhIGF-I directly to the newly forming bone through infusion tubing routed subcutaneously from the pump to the distraction site. Serum concentrations of mouse IGF-I, human IGF-I, and osteocalcin were determined at the end of the study. RESULTS: New bone formation observed in DO gaps showed a significant increase in new bone formation in rhIGF-I-treated mice, irrespective of delivery route. However, detectable levels of human IGF-I were found only in the serum of animals receiving rhIGF-I systemically. Osteocalcin levels did not differ between controls and rhIGF-I-treated groups. CONCLUSIONS: Locally and systemically delivered rhIGF-I both produce significant increases in new bone formed in an aged mouse model in which new bone formation is normally markedly impaired, suggesting that rhIGF-I may improve senile osteoporosis. Because systemic administration of IGF-I can result in untoward side effects, including an increased risk for cancer, the findings that locally delivered IGF-I improves bone regeneration without increasing circulating IGF-I levels suggests that this delivery route may be preferable in an at-risk, aged population.
PMID: 16939394 [PubMed - indexed for MEDLINE]


Effects of local administration of GH and IGF-1 on longitudinal bone growth in rats.Isgaard J, Nilsson A, Lindahl A, Jansson JO, Isaksson OG.
The effect of local administration of growth hormone (GH) and insulinlike growth factor 1 (IGF-1) on longitudinal bone growth was studied in the proximal tibia of hypophysectomized rats, by using the tetracycline method. Human GH (hGH) stimulated local bone growth when administered into the epiphysial growth plate, into the epiphysis through an implanted cannula, or into the knee joint intraarticularly. In contrast, hGH administration into the metaphysis did not cause such a stimulation. The effect of hGH was dose dependent, and the lowest daily dose of hGH that caused a stimulation was 50 ng. hGH produced by cloned bacteria was as effective as pituitary-derived hGH, excluding the possibility of a pituitary growth factor being the active compound. GH from other mammalian species (rat GH, ovine GH, and bacterially produced bovine GH) also stimulated local bone growth. Ovine prolactin (oPRL) stimulated local bone growth but the threshold dose of oPRL was approximately 100 times higher than that of hGH, suggesting that contamination of this preparation by GH may account for the stimulation. Reduced carboxymethylated human GH, that has a greatly reduced anabolic activity, did not stimulate local bone growth. Local administration of 5 micrograms of bacterially produced human IGF-1 per day produced a small but significant effect on unilateral bone growth. Simultaneous administration of hGH had no additive effect with, nor did it potentiate, the stimulatory effect of IGF-1. The present study confirms and extends earlier investigations, showing that local injection of GH at the site of the epiphysial growth plate stimulates unilateral bone growth. The study also shows that local administration of IGF-1 stimulates longitudinal bone growth.

[jdavis2007]

Yes, yes it does...from what I understand. I will be partaking in that peptide later this summer.

[fred9]

I also thiink this is quite interesting...most of the igf in your body is produced by the muscle itself instead of the liver..and the produced IGF is mostly utilized by the active muscle itself:

Changes in muscle mass and phenotype and the expression of autocrine and systemic growth factors by muscle in response to stretch and overload

--------------------------------------------------------------------------------
GEOFFREY GOLDSPINK a1 c1
a1 Department of Anatomy and Developmental Biology, Royal Free and University College Medical School, London, UK

Abstract


The study of the underlying mechanisms by which cells respond to mechanical stimuli, i.e. the link between the mechanical stimulus and gene expression, represents a new and important area in the morphological sciences. Several cell types (‘mechanocytes’), e.g. osteoblasts and fibroblasts as well as smooth, cardiac and skeletal muscle cells are activated by mechanical strain and there is now mounting evidence that this involves the cytoskeleton. Muscle offers one of the best opportunities for studying this type of mechanotransduction as the mechanical activity generated by and imposed upon muscle tissue can be accurately controlled and measured in both in vitro and in vivo systems. Muscle is highly responsive to changes in functional demands. Overload leads to hypertrophy, whilst decreased load force generation and immobilisation with the muscle in the shortened position leads to atrophy. For instance it has been shown that stretch is an important mechanical signal for the production of more actin and myosin filaments and the addition of new sarcomeres in series and in parallel. This is preceded by upregulation of transcription of the appropriate genes some of which such as the myosin isoforms markedly change the muscle phenotype. Indeed, the switch in the expression induced by mechanical activity of myosin heavy chain genes which encode different molecular motors is a means via which the tissue adapts to a given type of physical activity. As far as increase in mass is concerned, our group have cloned the cDNA of a splice variant of IGF that is produced by active muscle that appears to be the factor that controls local tissue repair, maintenance and remodelling. From its sequence it can be seen that it is derived from the IGF gene by alternative splicing but it has different exons to the liver isoforms. It has a 52 base insert in the E domain which alters the reading frame of the 3[prime prime or minute] end. Therefore, this splice variant of IGF-1 is likely to bind to a different binding protein which exists in the interstitial tissue spaces of muscle, neuronal tissue and bone. This would be expected to localise its action as it would be unstable in the unbound form which is important as its production would not disturb the glucose homeostasis unduly. This new growth factor has been called mechano growth factor (MGF) to distinguish it from the liver IGFs which have a systemic mode of action. Although the liver is usually thought of as the source of circulating IGF, it has recently been shown that during exercise skeletal muscle not only produces much of the circulating IGF but active musculature also utilises most of the IGF produced. We have cloned both an autocrine and endocrine IGF-1, both of which are upregulated in cardiac as well as skeletal muscle when subjected to overload. It has been shown that, in contrast to normal muscle, MGF is not detectable in dystrophic mdx muscles even when subjected to stretch and stretch combined with electrical stimulation. This is true for muscular dystrophies that are due to the lack of dystrophin (X-linked) and due to a laminin deficiency (autosomal), thus indicating that the dystrophin cytoskeletal complex may be involved in the mechanotransduction mechanism. When this complex is defective the necessary systemic as well as autocrine IGF-1 growth factors required for local repair are not produced and the ensuing cell death results in progressive loss of muscle mass. The discovery of the locally produced IGF-1 appears to provide the link between the mechanical stimulus and the activation of gene expression.

[jdavis2007]

That is why it is preferably administered via IM injection to a muscle you JUST got done working out. I have heard 5 minutes PWO. I will be taking 2 insulin syringes (each would have 50mcg) and inject in the bathroom PWO at my gym. I will have the two darts and several cotton swabs in a sunglass holder that I can just put in my pocket and take care of my business. If there was any other feasible way I would do it another way, but I will have to do this until I get another house with a bigger garage and I have my own gym. It is ultimately pretty unethical, but I am very clean and I don't hurt anybody. It should work well.

[jdavis2007]

2 darts for bilateral bodyparts by the way (left calf/right calf)...

[BITTAPART2]

this study doesnt seem to deal w/ LR3 IGF-1.

[spywizard]

That is why it is preferably administered via IM injection to a muscle you JUST got done working out. I have heard 5 minutes PWO. I will be taking 2 insulin syringes (each would have 50mcg) and inject in the bathroom PWO at my gym. I will have the two darts and several cotton swabs in a sunglass holder that I can just put in my pocket and take care of my business. If there was any other feasible way I would do it another way, but I will have to do this until I get another house with a bigger garage and I have my own gym. It is ultimately pretty unethical, but I am very clean and I don't hurt anybody. It should work well.

nothing sneaky about that..

http://www.medicalwatches.com/dicase.html

[spywizard]

they make them insulated as well

[Maldorf]

this study doesnt seem to deal w/ LR3 IGF-1.

Exactly. There is absolutely no site growth caused by injecting LR3 IGF-1. If youre using it because of that reason, just forget it.

[fossilfuel7]

Exactly. There is absolutely no site growth caused by injecting LR3 IGF-1. If youre using it because of that reason, just forget it.

What kind does?

[jdavis2007]

Anthony Roberts seems to think there is localized site growth with IGF-Lr3...and from everyone that has taken it that I am in contact with...they feel (and they look) like it helps lagging bodyparts...

[Maldorf]

What kind does?

Just plain old IGF. Ive read that when that was all that was available, people did get some local response. Idea here is that it doesnt last long enough in the body to make it much past the muscle you inject it. With the long IGF, it lasts long enough that it goes throughout the entire body.

[Maldorf]

Anthony Roberts seems to think there is localized site growth with IGF-Lr3...and from everyone that has taken it that I am in contact with...they feel (and they look) like it helps lagging bodyparts...

Believe me, it doesnt cause local growth. Anyone that has used it and claims so is fooling themselves. I did 2 four week cycles of it and got decent results over my entire body. I did 80 mcg/day divided into 2 injections. One in the morning and one preworkout. I did EVERY INJECTION, yes thats like 60 injections, into my lagging left bicep. That was just one cycle, I did 2. So I did a total of about 120 injections into that bicep. Yes it swells some after injection due to inflamation and looks bigger, but after all the smoke clears it grew no more than my other arm. Many others have had similar experiences.

[thebrakes]

Believe me, it doesnt cause local growth. Anyone that has used it and claims so is fooling themselves. I did 2 four week cycles of it and got decent results over my entire body. I did 80 mcg/day divided into 2 injections. One in the morning and one preworkout. I did EVERY INJECTION, yes thats like 60 injections, into my lagging left bicep. That was just one cycle, I did 2. So I did a total of about 120 injections into that bicep. Yes it swells some after injection due to inflamation and looks bigger, but after all the smoke clears it grew no more than my other arm. Many others have had similar experiences.

agreed. LR3 gives you a pump but no hypertrophy is induced locally (systemically, it's great). i wont call everyone a fool who says otherwise, because there may be a very small local effect from the LR3 spending ever-so-slightly more time in the injected muscle.