posted May 25, 2000 04:42 PM            

just an update:

as most of you know, i was admnestering hgh at 4 iu's a day for 20 days. half way through the hgh use, i added creatine to the mx. it has been 5 days since i have stopped the hgh and 7 days since i stopped the creatine(due to kidney pains). i very much liked the effects of creatine as i held lots of water and looked a lot bigger my strength went up also. at one point i weighed in at 198.5. this i attribute to the water from the creatine. i am no longer holding water and have just weighed myself. remember that i had been struggling at 190 lbs for about 3 months with no increases. this morning i weighed in at 194.5. i attribute the gain to both hgh and creatine. i have also received many comments on my "size". i decided to take a 10 day break from hgh before i started up at 9 iu's a day with lots of test. i will be starting hgh therapy with test in about 5 days. in conclusion, i gained 4.5 lbs of muscle from the hgh and creatine stack and my overall poundages are up. of course this was of a very short duration but thought i would report the results anyways.

posted May 25, 2000 04:50 PM            

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"Death will come in a wave of blue fury and that fury will be us!" poppa smurf at yesterdays speach.

posted May 26, 2000 12:02 PM            

The system that regulates all these hormone like HGH, igf-1,2, SHBG, test, insulin, IGFBP-1:6, t3/4: is very complicated and its almost imposible to just take lets say igf-1 and grow because your body will compansate other factors that will prevent your body from growing.

When you take GH from what I remember your t3 levels drop. Insulin resistance increases. IGF-1 levels increase. IGFBPs which bind igf-1 increases....among many many other things. And only a delicate balance of these hormones will cause growth.

So basically no one knows what exactly is happening to achive growth from GH but to get best results it has been know that you need to take T3 and insulin among an increased cal intake, like 5kcal/day.

Here are some abstracts that i have collected that show the relationship.

Effects of androgens on the insulin-like growth factor system in an androgen-responsive human
osteoblastic cell line.

Gori F, Hofbauer LC, Conover CA, Khosla S

Endocrine Research Unit, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.

Although androgens have significant effects on bone metabolism, the mediators of their effects are still unclear. As the insulin-like growth factors (IGFs) and
IGF-binding proteins (IGFBPs) have important effects on osteoblast proliferation and differentiation, we examined androgen effects on the IGF system in a
conditionally immortalized human fetal osteoblastic cell line, hFOB/AR-6, which displays a mature osteoblastic phenotype and physiological levels of functional
androgen receptors. The nonaromatizable androgen, 5alpha-dihydrotestosterone (5alphaDHT), and testosterone, but not dehydroepiandrosterone, increased IGF-I
messenger RNA (mRNA) levels up to 4-fold in a dose (10(-12)-10(-6) M)- and time (2-72 h)-dependent fashion. These changes were prevented by the specific
androgen receptor antagonist, hydroxyflutamide. In addition, 5alpha-DHT decreased IGFBP-4 mRNA and protein levels by 2- and 4-fold, respectively, and
increased IGFBP-2 and -3 mRNA and protein levels by 6- and 7-fold (for mRNA) and 3- and 5-fold (for protein), respectively. hFOB/AR-6 cells expressed the
type-I IGF receptor, but this was not regulated by 5alphaDHT. 5alphaDHT and IGFBP-3 specifically increased hFOB/AR-6 cell proliferation, and a monoclonal
antibody specific for IGF-I blocked this effect. Thus, androgens increase the expression of IGF-I, IGFBP-2, and IGFBP-3, but decrease levels of the inhibitory
IGFBP-4 in an androgen-responsive human osteoblastic cell line. Our data are consistent with the hypothesis that the effects of androgen on bone cells may be
mediated at least in part by increases in IGF-I production and by differential regulation of IGFBPs.

Role of insulin-like growth factor binding proteins in controlling IGF actions.

Clemmons DR

Division of Endocrinology, The University of North Carolina, Chapel Hill 27599-7170, USA.

The insulin-like growth factors (IGF) stimulate growth in multiple connective tissue cell types. The capacity of IGF-I and -II to access cell surface receptors is
controlled by insulin-like growth factor binding proteins (IGFBPs). Connective tissue cells synthesize four of the IGFBPs (IGFBP-2 through -5). Synthesis is
controlled by growth hormone and several other growth factors. In addition to regulating synthesis, other variables regulate the abundance of the IGFBPs including
specific serine proteases that are produced for each form of IGFBP. Following cleavage, the IGFBPs have reduced affinity for IGF-I and -II, thus allowing release
to receptors. Variables that regulate the amount of proteolysis have been shown to regulate IGF action. In addition to being proteolytically cleaved, three forms of
IGFBPs (IGFBP-2, -3 and -5) can associate with extracellular matrix (ECM). In the case of IGFBP-5 binding to ECM, its affinity is lowered substantially allowing
IGF to better equilibrate with the receptors. This event results in a potentiation of IGF-I action on fibroblasts and smooth muscle cells (SMC). In summary, IGFBPs
are important molecules for regulating the bioavailability of IGF-I and -II to receptors. Understanding the variables that regulate their abundance may lead to a better
understanding of the factors that regulate IGF action in skeletal tissues.

Insulin-like growth factor binding proteins and their role in controlling IGF actions.

Clemmons DR

Department of Medicine, University of North Carolina, School of Medicine, Chapel Hill 27599, USA.

The insulin-like growth factor binding proteins (IGFBPs) are a family of six proteins that bind to insulin-like growth factor-I and -II with very high affinity. Because
their affinity constants are between two- and 50-fold greater than the IGF-I receptor, they control the distribution of the IGFs among soluble IGFBPs in interstitial
fluids, IGFBPs bound to cell surfaces or extracellular matrix (ECM) and cell surface receptors. Although there are six forms of insulin-like growth factor binding
proteins, most interstitial fluids contain only three or four forms, and usually only one or two predominate. The proteins differ significantly in their biochemical
characteristics, and this accounts for many of the differences that have been observed in their biological actions. Several different types of protease cleave these
binding proteins. Proteolytic cleavage generally inactivates the binding proteins or reduces their ability to bind to IGF-I or -II substantially. Several cell types have
been shown to secrete these proteases; therefore, the factors that regulate protease activity can control binding protein actions indirectly. Other post-translational
modifications, such as glycosylation and phosphorylation, have been shown to alter IGF binding protein activity. While binding protein actions have been studied
extensively in vitro, many of the in vivo activities of these proteins remain to be defined.

Functional role of insulin-like growth factor binding proteins.

Ranke MB, Elmlinger M

University Children's Hospital, Tubingen, Germany.

Insulin-like growth factors (IGF-I, IGF-II) are important regulators of cell division and differentiation. In their free form, IGFs form a complex with specific binding
proteins (IGFBPs), six of which have now been characterized. These IGFBPs differ in their ability to bind IGF-I and/or IGF-II, and, depending on their location and
metabolic circumstances, they inhibit or augment IGF action to varying extents. New findings have changed our understanding of IGFBPs, which are now considered
to be major regulators of IGF action and IGF transport proteins between compartments. Recently, the IGF-independent action of IGFBPs was discovered. Levels
of IGFBP-3, for instance, are important indicators of states of altered growth hormone secretion and action, as well as being important during treatment with growth
hormone or IGF-I. IGFBP-1 and -2 levels reflect changes related to nutrition, insulin secretion, foetal development and malignant state. The unravelling of the
intricate interactions of IGFs, IGFBPs and their targets is bound to influence our understanding of the physiology and development of biological systems. Likewise,
the possibility of regulating the IGFBP system is likely to open up new fields in the treatment of diseases in the future.

The insulin-like growth factor binding protein superfamily: new perspectives.

Rosenfeld RG, Hwa V, Wilson L, Lopez-Bermejo A, Buckway C, Burren C, Choi WK, Devi G, Ingermann A, Graham D, Minniti G, Spagnoli A, Oh
Y

Department of Pediatrics, Oregon Health Science University, Portland, Oregon 97201, USA. [email protected]

The insulin-like growth factor (IGF) binding proteins (IGFBPs) were initially identified as carrier proteins for IGF-I and IGF-II in a variety of biologic fluids. Their
presumed function was to protect IGF peptides from degradation and clearance, increase the half-life of the IGFs, and deliver them to appropriate tissue receptors.
The concept of IGFBPs as simple carrier proteins has been complicated, however, by a number of observations: 1) the six IGFBPs vary in their tissue expression
and their regulation by other hormones and growth factors; 2) the IGFBPs are subjected to proteolytic degradation, thereby altering their affinities for the IGFs; 3)
IGFBP-3 and IGFBP-5, in addition to binding IGFs, also can associate with an acid-labile subunit, thereby increasing further the half-life of the IGFs; 4) in addition
to modifying the access of IGF peptides to IGF and insulin receptors, several of the IGFBPs may be capable of increasing IGF action; 5) some of the IGFBPs may
be capable of IGF-independent regulation of cell growth; 6) some of the IGFBPs are associated with cell membranes or possibly with membrane receptors; and 7)
some of the IGFBPs have nuclear recognition sites and may be found within the nucleus. Additionally, a number of cDNAs identified recently have been found to
encode proteins that bind IGFs, but with substantially lower affinities than is the case with IGFBPs. The N-terminal regions of the predicted proteins are structurally
homologous to the classic IGFBPs, with conservation of the cysteine-rich region. These observations suggest that these low-affinity binders are members of an
IGFBP superfamily, capable of regulating cell growth by both IGF-dependent and IGF-independent mechanisms.insulin-like growth factor, insulin-like growth factor
binding proteins.

Serum free IGF-I, total IGF-I, IGFBP-1 and IGFBP-3 levels in an elderly population: relation to
age and sex steroid levels.

Janssen JA, Stolk RP, Pols HA, Grobbee DE, de Jong FH, Lamberts SW

Department of Internal Medicine III, Erasmus University, Rotterdam, The Netherlands.

BACKGROUND: Most previous studies concerning the relationship between IGF-I and age used assays measuring total IGF-I. Although free IGF-I is considered
of greater biological relevance, little is known about its relationship with sex steroids levels in elderly healthy subjects. MEASUREMENTS: In a cross-sectional
study of 218 healthy people (103 men, 115 women) aged 55-80 years we measured serum total and free IGF-I, IGFBP-1 and IGFBP3 levels and sex steroids.
Free androgen index and free oestradiol index were used as an indicator for free oestradiol and free testosterone levels, respectively. RESULTS: Free IGF-I levels
did not decline with age in the whole study population. Free IGF-I levels even increased in individuals above 70 years of age in comparison to those aged between
55 and 70 years (mean +/- SE 0.106 +/- 0.007 nmol/l vs. 0.086 +/- 0.004 nmol/l, P = 0.009). Total IGF-I and IGFBP-3 decreased with age (r = -0.20, P = 0.005
and r = -0.24, P = 0.001, respectively). Total IGF-I levels were positively related with free oestrogen index in both sexes. Free IGF-I did not relate to free
oestrogen or androgen index. In women only, free IGF-I was related positively with DHEAS while IGFBP-1 was inversely correlated with DHEAS.
CONCLUSIONS: Free IGF-I levels do not decrease with age and are even higher in individuals above 70 years. There was no relationship between free IGF-I and
free androgen or oestrogen index in either gender. We hypothesize that higher free IGF-I levels in older persons may be the consequence of selective survival in the
cohort: subjects with high free IGF-I levels may live longer. The absence of a relationship between free IGF-I levels and free androgen and oestrogen indices
suggests that there is no direct interaction between the biological activity of circulating IGF-I levels and sex hormone production in a healthy ageing population.

Free insulin-like growth factor I (IGF-I) in healthy subjects: relationship with IGF-binding
proteins and insulin sensitivity.

Nyomba BL, Berard L, Murphy LJ

Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.

The majority of insulin-like growth factor I (IGF-I) circulates in blood bound to a family of IGF-binding proteins (IGFBPs). Only a small fraction of IGF-I is
unbound or free, and one of the postulated roles of the IGFBPs is regulation of this free component, thereby increasing IGF-I bioavailability. Whether free IGF-I
plays a physiological role in glucose homeostasis, however, is not clear. In this study, we examined the effects of acute changes in serum insulin on free IGF-I, total
IGF-I, IGFBP-1, and IGFBP-3 in 11 healthy subjects. Glucose (0.3 g/kg) and insulin (0.05 U/kg) were injected iv at 0 and 20 min, respectively. Blood samples
were drawn at defined intervals for 3 h, and insulin sensitivity (SI) was computed by Bergman's minimal model. Serum insulin reached a first peak after glucose
injection and a second, higher peak after exogenous insulin administration. Although the total IGF-I level remained constant for the duration of the experiment, free
IGF-I decreased by 20% 20 min after the first insulin peak and by 35% 20 min after the second peak. IGFBP-1 first declined to 20% below basal, then rose to
3-fold the basal level. IGFBP-3 increased linearly to 20% above basal by the end of the experiment, and this increase mirrored the decline of free IGF-I. In the
fasting state, free IGF-I was positively correlated with SI (r = 0.52; P < 0.005) and inversely correlated with glucose (r = -0.51; P < 0.005) and IGFBP-1 (r =
-0.65; P < 0.001). In conclusion, free IGF-I is acutely regulated by insulin and correlates with SI, suggesting that it may play a physiological role in glucose
homeostasis.

Effect of marathon run on serum IGF-I and IGF-binding protein 1 and 3 levels.

Koistinen H, Koistinen R, Selenius L, Ylikorkala Q, Seppala M

Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland.

Acute physical exercise increases growth hormone (GH) secretion, and GH regulates the expression of insulin-like growth factor I (IGF-I) and IGF-binding protein
(IGFBP) 3. IGFBP-1 is a local modulator of IGF activity with rapid dynamic regulation that is downregulated by insulin. The IGF system mediates the metabolic
actions of GH, and possibly it regulates glucose metabolism. We hypothesize that strenuous exercise causes changes in the IGF system. We studied the effects of the
marathon run on the circulating levels of IGF-I, IGFBP-1, IGFBP-3, and insulin in 23 participants. Immediately after the run, the most striking change was an
11.6-fold median increase in serum IGFBP-1 level (from 63.7 +/- 50.5 to 736 +/- 408 micrograms/l; P < 0.001). Because the insulin level remained unchanged, the
elevation of serum IGFBP-1 level cannot be explained by changes in insulin. One day after the run, the IGFBP-1 level had returned to baseline. The physiological
role of this increment could be the inhibition of hypoglycemic effects of IGF-I and/or regulation of glucose availability to the muscles. The changes in IGF-I and
IGFBP-3 levels were less dramatic: the IGF-I and IGFBP-3 levels were lower 1 and 3 days after the run. This report provides an important basis for authentic
effects of strenuous exercise on the IGF-system.

Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants,
children, and adolescents: the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass
index, and pubertal maturation.

Juul A, Dalgaard P, Blum WF, Bang P, Hall K, Michaelsen KF, Muller J, Skakkebaek NE

University Department of Growth and Reproduction GR, Rigshospitalet, Denmark.

Circulating IGF-I and -II are bound to specific insulin-like growth factor (IGF)-binding proteins (IGFBPs), of which IGFBP-3 binds the majority of the IGFs.
IGFBP-3 levels are regulated by GH and have been suggested to provide additional information on GH secretory capacity compared to IGF-I. However, the
diagnostic value of IGFBP-3 is still controversial, perhaps because the quality of the available normative data for IGFBP-3 varies. It has recently been shown that a
large number of individuals is required to establish reference ranges for IGF-I that take into account age, sex, body mass index (BMI), and pubertal stage.
Therefore, we measured IGFBP-3, IGF-I, IGF-II, IGFBP-1, and IGFBP-2 levels by RIA in 907 healthy children to establish well characterized normative data on
IGFBP-3 according to age, sex, and pubertal stage and to study the complex relationship between IGFs and their BPs in puberty. We found that IGFBP-3 levels
increase with age in children, with maximal levels in puberty; girls experience peak values approximately 1 yr earlier than boys. Age, sex, height, BMI, and pubertal
maturation were all important factors in determining the circulating levels of IGFBP-3, whereas IGF-I levels were unaffected by BMI. Comparison of IGFBP-3 with
IGF-1 concentrations revealed that they did not exhibit the same developmental pattern in puberty. IGF-I levels increased to relatively higher levels than IGFBP-3,
leading to an increasing molar ratio between IGF-I and IGFBP-3 in puberty, when growth velocity is high. Concomitantly, IGF-II and IGFBP-2 levels were
unchanged throughout puberty, whereas IGFBP-1 levels declined with age in prepubertal children, with lowest values in puberty. There was a highly significant
correlation between IGF-I and -II and IGFBP-3 on a molar basis (r = 0.84; P < 0.0001). Thus, we speculate that IGFBP-3 is pivotal for circulating IGF bioactivity
and that the increase in the molar ratio between IGF-I and IGFBP-3 reflects an increase in free, biologically active IGF-I. In conclusion, we have provided
normative data on a large group of healthy individuals and conclude that age, sex, height, BMI, and pubertal maturation have to be taken into account before a single
IGFBP-3 value in a growth-retarded child can be evaluated properly.

Acute effect of brief low- and high-intensity exercise on circulating insulin-like growth factor
(IGF) I, II, and IGF-binding protein-3 and its proteolysis in young healthy men.

Schwarz AJ, Brasel JA, Hintz RL, Mohan S, Cooper DM

Department of Pediatrics, UCLA Medical Center, Torrance 90509, USA.

We measured circulating levels of the GH insulin-like growth factor (IGF) system in response to brief exercise of different intensities. Ten males (mean age 28 +/- 5
yr) were studied on three separate occasions: once under resting conditions (control) and once each performing 10 min of low- or high-intensity exercise. Blood
samples were assayed by RIA for GH, IGF-I and -II, IGF-binding protein-3 (IGFBP-3), and IGFBP-3 proteolytic activity. After 10 min of low-intensity exercise,
IGF-I and IGFBP-3 had increased over preexercise baseline by 7.7 +/- 2.7% (P < 0.05) and 12.5 +/- 3.3% (P < 0.004), respectively. After 10 min of
high-intensity exercise, all measured components of the IGF system were increased: IGF-I by 13.3 +/- 3.2% (P < 0.002), IGF-II by 15.7 +/- 3.1 (P < 0.01), and
IGFBP-3 by 23 +/- 6% (P < 0.001). IGFBP-3 proteolytic activity also was increased (44 +/- 14% above baseline, P < 0.05). GH reached its peak 10 min after
the cessation of high-intensity exercise, unlike the earlier peaks of IGF-I and II. In summary: 1) brief exercise leads to small but significant increases in circulating
IGF-I, IGF-II, IGFBP-3, and IGFBP-3 proteolysis; and 2) these responses may be influenced by exercise intensity. The IGF responses seem to be unrelated to
GH. Acute exercise-induced proteolysis of IGFBP-3 may contribute to anabolic effects of physical activity by increasing the bioavailability of IGF-I.

Testosterone administration increases insulin-like growth factor-I levels in normal men.

Hobbs CJ, Plymate SR, Rosen CJ, Adler RA

Department of Clinical Investigation, Madigan Army Medical Center, Tacoma, Washington 98493.

Although testosterone (T) administration can increase insulin-like growth factor-I (IGF-I) when administered to hypogonadal men, no studies have examined whether
this occurs in normal men. The present study was undertaken to determine if an increase in IGF-I may be part of the anabolic effect of androgens. We enrolled 11
normal men in a randomized, double-blinded cross-over study. Subjects were assigned to receive either T enanthate (TE) (300 mg im, each week) or nandrolone
(ND) decanoate (300 mg im, each week) for 6 weeks. After a washout period subjects were administered the alternate treatment. Pre- and posttreatment serum
was analyzed for IGF-I by RIA after acid-ethanol extraction. Results expressed as mean +/- SEM (Table 1). IGF-binding protein-3 was measured by RIA and was
unchanged in the TE treatment and decreased significantly after ND treatment. Although GH levels were not significantly different after either TE or ND treatment,
they tended to increase after TE treatment (1.23 +/- 0.28 ng/mL vs. 3.3 +/- 1.03 ng/mL) but remained unchanged after ND treatment (1.68 +/- 0.68 ng/mL vs. 1.89
+/- 0.64 ng/mL). Serum total T levels increased 32 +/- 0.05 nmol/L in the TE-treated men, but fell by 7 +/- 0.02 nmol/L in the ND-treated men (P < 0.0001).
Serum estradiol levels rose by 193.04 +/- 19.82 pmol/L in the TE-treated men although falling by 50.65 +/- 34.50 pmol/L in the ND-treated men (P < 0.0002).
These data indicate that when normal men are given TE, serum IGF-I levels increase after 6 weeks of treatment. Treatment with ND did not change serum levels of
IGF-I but did decrease the level of the major serum IGF-BP and therefore the level of bioavailable IGF-I may be increased in the ND group.

[This message has been edited by Milk_Man (edited May 26, 2000).]