Latest Research on IGF, Growth Hormone, Insulin and Site Specific Response
by Author L. Rea
Publication Date: April 22, 2003
Nothing in this article is intended to take the place of advice from a licensed health professional. Consult a physician before taking any medication.
Q1:
sir , you suggest best way of GH use is to inject it directly in the muscle group trained that day , this is site specific application u say (page 116) , now we know all the conversion of GH to IGF-1 is done in the liver, so what benefits are u mentioning here cos site increase og-1, or MGF is not going to happen , so what’s the use of this method ?
2)u also suggest post workout GH injects (page 117) , now , frank is using Humulin post workout which is active I think for 6 hrs or so , now ure suggesting gh shot an hour after the slin shot , he wudve also got in his huge protein shake, carbs etc with his post workout slin shot , simply means insulin levels are very high . its common knowledge gh doesnt work in high insulin environment , as they contradict each other , so arent we wasting a gh shot here ??
Q2: sir , in most of ur writings , u mention the hepatic liver production a lot and seem to give it a lot of importance , recent studies show that increased hepatic-1 is linked with cancer development(growth of unwanted cells ) and it seems like localised-1 and mgf is much more important , also , in a study done in rats that are engineered not to produce hepatic IGF, growth of the rats, including skeletal muscle development, is still normal. This sugggests that liver produced IGF is not very significant for muscle development.
this itself is enough to show liver-1 is playing very lil role, if any in muscle hypertrophy , isnt it sir ?
A: Interesting contradictive questions to say the least. You appear to be suggesting that localized IGF-1 formation is non-existent yet more effective for building muscle as well. Hmmm. Okay!
In truth research has validated on several occasions that GH and insulin do indeed have a site-specific response of anabolism on target tissues. The fact remains that it is the interaction between GH and insulin that allows for the formation of somatomedins such as IGF-1…which is part of the synergistic response.
The issue concerning cancer is moot as we are discussing a single source of origin for IGF-1 as if it were actually a fact to come to this supposition. Cancer cells produce a great deal of IGF-1 themselves.
We will talk about rats in a moment but I think it is time for a basic review of factual information.
The Latest Research on IGF, Growth Hormone, Insulin…and Site Specific Response
A Brief Lesson To Help Catch Up First
It seems reasonably certain the almost every hard-core and serious athlete is aware of the paramount importance of testosterone and growth hormone (GH) for actualizing gains in lean mass tissue. Unfortunately it seems that not as many are aware of insulin's powerful and symbiotic anabolic effects. This is especially so in regards to its synergistic role in producing one of the body's most potent growth factors called IGF-1 (Insulin-like Growth Factor-1).
Any enhanced athlete could employ the best coaches and training protocols while utilizing polypharmacology yet realize only a fraction of their muscle mass potential unless they realize the facts about interaction between GH, insulin and IGF-1.
The amount of hepatic and site specific IGF-1 the body secretes is dependent upon insulin management.
The ratio and interaction between GH, insulin and IGF-1 is paramount for correct and maximum protein and glucose metabolism.
Many do not realize that IGF-1 is so powerful that it has even been documented to reverse age related metabolic inhibitors such as insulin resistance and muscle loss while improving muscular contractile force.
Hepatic and tissue specific IGF-1 formation is optimized by a more steady tide effect circulatory exchange/interaction between GH and insulin.
Intense training increases testosterone, GH and IGF levels. However it also decreases insulin levels and increases cortisol (the catabolic muscle breakdown hormone)
Whenever insulin is low the life of GH-IGF secretion is short lived.
Heavy, eccentric weight training causes the highest increases in circulating bioactive IGF-1.
GH release via sleep, supplements or exogenous administration is useless without sufficient circulating insulin and blood amino acids.
Huh?
Human secretion of GH occurs from the pituitary gland (which is found at the base of the brain). Some travels the vascular system to muscle and bone tissue resulting in direct initiation of anabolism through alternate growth factor/somatomedin formation (IGF-1&2 are formed due to cascade responses). Some travels to the liver where it interacts with insulin and other factors to form hepatic introduced circulatory growth factors/somatomedins.
Once in circulation both IGF-I and IGF-2 have very short lives. IGF-II is predominantly responsible for nerve growth. IGF-I exerts most of its profound growth effects on muscle. Unless an individual actuates both insulin and IGF circulating in the correct amounts, muscle growth will be about zero.
Consider the Obvious…
It was from research performed on diabetics that initially provided the earlier examples. Insulin-dependant diabetics have chronic low IGF levels both circulatory and site-specific. They also commonly have a very bad time when attempting to increase muscle mass. Realize that diabetes is a disease of inconsistent, ineffective insulin secretion by the pancreas. A diabetic's circulatory insulin level is always going up and down depending on how much they administer and what they eat…and always mistimed to GH release. It's almost impossible to keep constant during the right periods thus resulting in little IGF formation.
Intense Training and local IGF-1 response…
Previous research has shown conflicting results with regard to IGF-1 secretion and exercise of various types. However, recent research has demonstrated that that a large amount of IGF-1 is secreted within the first 12 minutes of intense training protocols.
Properly designed current research also has shown that muscle tissue employed in weight training produced a great deal more bioactive IGF-1 (locally) and that IGF-1 circulates in a sort of "system" consisting predominantly of a group of six binding proteins, free IGF-1 and an acid-labile unit. Did you know that these six binding proteins in blood and muscle alike regulate the biological activity (usability) of IGF-1? (Say what?)
The latest body of research on IGF-1 validates that intense weight training induces a signal within muscle causes a
rearranging effect to the ratio of these binding proteins that results in increased activity and availability of IGF-1. This appears to be essential to the growth and repair process…or Action/Reaction Factors.
In fact, he total amount of IGF-1 secreted by any means is not as important as the
rearrangement of the IGF-1 binding protein ratio itself. Heavy resistance training triggers this rearrangement quite nicely of course as it is one of the strongest adaptive response actions there is. By the way, big issue here, this modulation of the IGF-1 binding proteins to create active IGF-1 is not fully realized until six to 12 hours after training. Hmmmm, and this just happens to be about the same time that peak muscle protein synthesis rates occur. Are you starting to see the timing and connection?
So What have we (Hopefully) learned so far?
Without proper timing of the insulin supply, kept within a narrow physiological range, GH levels are quickly destroyed and the active-life of IGF-I is sadly short lived. Precisely prolonged circulatory insulin levels prolong the active life of IGF and GH secretion so their powerful effects on muscle likely last longer.
Even though there is a great deal of IGF-1 present a maximum growth stimulus is require to alter the binding proteins ratio as a means of optimizing the amount of bio-active IGF-1.
Without proper timing of insulin and GH introduction IGF formation is reduced or lost and we look like a weenie-boy.
Now that we have the basics out of the way let’s look at some other points of consideration.
It appears that for some the question of hepatic vs. local IGF formation and GH utilization is still a question. Though several exist the studies below eliminate this misperception.
Effects of local administration of GH and IGF-1 on longitudinal bone growth in rats
J Isgaard, A Nilsson, A Lindahl, J O Jansson, O G Isaksson
AMERICAN JOURNAL OF PHYSIOLOGY , 250(4 Pt 1):E367-E372 1986
The effect of local administration
of growth hormone (GH) and insulin-like 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.
So we have rat bones that grow in response to IGF-1 and GH administered locally (site-specific)? Ya, but what about the humans that are not rats? Is it the same reaction to the same action? And is IGF-1 formed in places other than the liver?
Autocrine regulation of cell proliferation and secretion of insulin-like growth factor I (IGF-I) in osteoblastic cell line MC3T3-E1]
F Trémollières, S Mohan, C Ribot
ANNALES D ENDOCRINOLOGY , 55(2):95-102 1994
Bone cells maintained in culture produce different growth factors which modulate cell growth via a mechanism of auto/paracrine regulation. IGF-1 is abundantly produced by murine bone cells where it acts as a mitogenic agent. The aim of this work was to study the effect of IGF-II, TGF beta 1, basic FGF (FGFb) and PDGF on cell growth and production of IGF-1 in the murine osteoblastic clonal cell line MC3T3-E1. IGF-1 was assayed by RIA after elimination of the IGF binding proteins. After 24th of treatment in culture conditions without serum, incorporation of [3H] methylthymidine increased significantly in MC3T3-E1 treated with IGF-II, FGFb and PDGF. The effect was dose-dependent. At low cell density (2.5 X 10(4) cemm/cm2) and after 24 h treatment, IGF-II at 10 ng/ml led to a 220% increase in IGF-I production in MC3T3-E1 cells (9.5 +/- 1.5 vs 4.2 +/- 0.44 ng/micrograms protein, p < 0.001) while TGF beta 1, FGFb and PDGF at 1 ng/ml led to a significant decrease (65, 95 and 85% respectively) in IGF-I (TGF beta 1: 1.5 +/- 0.3 ng/micrograms; FGBb: 0.21 +/- 0.04 ng/micrograms; PDGF: 0.66 +/- 0.1 ng/micrograms; p < 0.001). Production of IGF-I was controlled by a dose-dependent relationship and varied as a function of incubation time and cell density. IGF-II led to an increase in mRNA coding for IGF-1 as early as the first hour after IGF-II addition with a maximal effect at 6 hours.
So other cells in the body do produce growth factors. But is it due to GH and Insulin exposure locally (site-specific) Oh, and where are the humans?
Regulation and action of insulin-like growth factors at the cellular level
L S Phillips, J B Harp, S Goldstein, C I Pao
Proceedings of the Nutrition Society , 49(3):451-458 1990
Present understanding of IGF-1 as a growth factor mediating integration of nutritional-hormonal interactions indicates that IGF-1 acts in both an endocrine mode on distant targets and an autocrine-paracrine mode on local targets. In the liver, the combined presence of GH, insulin, and critical metabolic fuels such as essential amino acids results in increased levels of IGF-1 messenger RNA, increased production of a high-MW IGF-1 precursor, and increased release of IGF-1 into the circulation, permitting action on distant target tissues bearing specific receptors for IGF-1. The net effect is distant amplification of anabolic hormone action via IGF-1 acting in an endocrine mode. In extrahepatic tissues, both 'general' anabolic hormones (insulin and GH) as well as 'specific' hormones (e.g. gonadotropins) acting on a wide variety of targets (including fibroblasts and chondrocytes as well as granulosa and Leydig cells) promote both local secretion of IGF-1 and an increase in IGF-1 receptors. Local actions of IGF-1 then result in a secondary increase in both hormone receptors and hormone responses. The net effect is local amplification of hormone action via IGF-1 acting as a growth factor in an autocrine-paracrine mode.
Other References:
1. Hertoghe T. Growth hormone therapy in ageing adults 4th Annual meeting of the American Academy of anti-aging Medicine, Las Vegas December 1996.
2. Bouillanne O, Rainfray M, Tissandier O et al. Growth hormone in elderly people: an age-delaying drug?
Fundan Clin Pharmacol 1996 10 (5) 416-30.
3. Merimee TJ. Growth hormone secretion and action.
Endocrinology DeGroot et al (eds) New York, NY 1979.
4. Thoren M, Hilding M, Baxter RR et al. Serum insulin like growth factor 1(IGF1), IGF binding protein -1 and -3 and the acid labile subunit as serum markers of body composition during growth hormone therapy in adults with GH deficiency.
J Clin Endorinol Metabol 1997; 82 (1): 223-8.
5. Johansson JO , Landin K, Johannsson G et al. Long term treatment with growth hormone decreases plasminogen acitivator and tissue plasminogen activator in growth hormone deficient adults.
Thromb Haemost 1996; 76 (3): 422-8.
6. Boonen S, Lesaffre E, Aerssens J. Deficiency of the growth hormone insulin like growth factor 1 axis potentially involved in age related abnormalities in body composition.
Gerontology 1996; 42 (6): 330-8.
7. Bengt-Ake Bengtsson. Effects of Growth Hormone Deficiency 4th Annual meeting of the American Academy of anti-aging Medicine, Las Vegas December 1996.
8. Jansen YJ, Frolich M, Roelfsema F. A low starting dose of genotropin in growth hormone deficient adults.
J Clin Endocrinol Metab 1997; 82 (1): 129-35.
9. Terry CL. Human growth hormone replacement therapy in adults 4th Annual meeting of the American Academy of anti-aging Medicine, Las Vegas December 1996.
10. Klatz R, MD Grow Young with HGH
Harper Collins New York, NY 1997.
11. Smith R. A new receptor involved in the control of growth hormone secretion 4th annual meeting American academy of anti-aging medicine Las Vegas 1996.
12. Kraemer WJ, Volek JS, Bush JA, et al. J.Appl.Physiol.85(4) 1544-1555,1998.
13. Daughaday WH,ed. Endocrine Control of Growth, New York:Elsevier,1981.
14. Tillmann V, Patel L, Gill MS, et al. Clin Endocrinol.53(3):329-336,2000.
15. Philips LS. Metabolism, 34:765-770,1985
16. Carroll PV, Christ ER, Umpleby AM, et al. Diabetes, 49(5):789-96,2000.
17. Zachwieja JJ, Yarasheski KE. Phys Ther. 79(1):76-82,1999.
18. Parkhouse WS, Coupland DC, Li C, Vanderhoek KJ. Mech Aging Dev.
77;113(2):75-83,2000.
19. Rasmussen BB, Tipton KD, Miller SL, et al. J.Appl.Physiol. 88:386-392,2000.
20. Jenkins PJ. Clin Endocrin. 50:683-689,1999.
21. Bamman MM, et al. Am J Physiol Endocrinol Metab. 280:E383-E390, 2001.
22. Nindl BC, et al. J Appl Physiol. 90:1319-1326, 2001.
|
