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For everyone thats tried cjc1295,I'm making it the focal point of my research
I'm with a lab that has the capability of making 98% pure or above,,note i could save 3grand an order by purchasing 95% but i wouldn't have bragging rights of which I know say I have the strongest cjc1295 available ..only the best will do.
Written by: M.M. a/k/a DatBtrue
Copyright 2008 by M.M. a/k/a DatBtrue
All rights reserved. No part of this article may be reproduced in any form without the written permission of the copyright owner.
Restoring Growth Hormone
"It has been argued that the age-dependent decline in sex steroid, Growth Hormone, and IGF-I production is nature’s way of protecting us from cancer and heart disease, but a far more likely scenario is that once we reach our reproductive capacity, nature begins programming us for death." - Roy G. Smith, Ph.D. Director, Huffington Center on Aging; Professor, Department of Molecular & Cellular Biology; former Vice President for Basic Research at Merck Research Laboratories, Merck & Co
Such programming begins as the second decade of life draws to a close, the negative consequences of which become more noticeable with each passing year.
We begin to experience a steady decline in immune function. (1,2) Our bodies increase production of glucocorticoids (catabolic hormones) and cytokines (inflammatory) which negatively impact metabolism, bone density, strength, exercise tolerance, cognitive function, and mood. (3,4–8)
The hormones of sex, dehydroepiandrosterone (DHEA), Growth Hormone (GH), and Insulin-like Growth Factor (IGF-1) are positively correlated with the health and well-being of the body in general and the specific functioning of metabolism, the cardiovascular system, the musculature skeletal system, cognitive function & the immune system. However these hormonal levels naturally decline as we age and as a consequence those systems necessary to maintain optimal health decline as well. (1-4,9)
"Hence, if we wish to maintain quality of life during aging we must oppose nature." - Roy G. Smith
A progressive decline in lean body mass, atrophy of its component organs & reduction in their function and increased deposition of adipose tissue mass characteristic of the aging human body result partially from the body's diminished secretion of growth hormone. (10-13) These negative changes resulting from growth hormone deficiency have been shown to be reversible by replacement doses of growth hormone. (14-21)
Growth Hormone is a vital anabolic hormone whose positive stimulatory effects on protein synthesis (particularly in the liver, muscle, bone, cartlidge, spleen, kidney, skin, thymus, and red blood cells) and on lipolysis (the breakdown of fat stored in fat cells) contributes greatly to growth, repair & well-being. (10)
Growth Hormone (GH) secretion is primarily regulated by the release of two peptides, Growth Hormone-Releasing Hormone (GHRH) and Somatostatin. The hypothalamus region of the brain releases these hormones in response to signals from the central nervous system. GHRH once released makes its way to the receptors on the somatotrope cells of the pituitary gland of the brain where it stimulates Growth Hormone release. Somatostatin once released makes its way to the receptors on the somatotrope cells of the pituitary gland of the brain where it inhibits Growth Hormone release. (15)
The primary physiological action of somatostatin is to inhibit synthesis and release of GH. (16-19) The primary physiological action of Growth Hormone-Releasing Hormone (GHRH) is to stimulate synthesis and release of GH.
The end product of this cascade, Growth Hormone (GH) once secreted exerts its effect in the body as a whole both directly and indirectly through its initiation of Insulin-like Growth Factor (IGF-1) synthesis in the liver. IGF-1 in turn exerts its effect in the body and its rise in turn begins to inhibit any further GH release.
Growth Hormone (GH) is released periodically within the body in a controlled pulsating fashion. This periodic pattern plays an important role in transmitting the GH "growth, repair & well-being" message to tissue. A review of several studies involving GH replacement in GH-deficient animals reveals the biological significance of episodic secretion. These studies conclude that GH released in a pulsatile pattern is far more efficient in improving mammalian growth and repair than the method of GH administration by constant infusion.
In males GH pulses occur approximately every three (3) hours, a frequency that appears across most mammals. The secretion bursts are preceded and followed by almost undetectable levels of plasma GH.
In females however GH pulses occur more frequently and the base level of plasma GH remains higher than males who have fewer GH pulses but the amplitude of which are more pronounced.
GH pulse amplitudes are increased during slow wave sleep such that particularly in males, most GH secretion occurs at night. (22)
Growth Hormone secretion is highest during the growing years of youth and early adulthood. In humans the secretion rate starts to noticeably decrease during the third decade of life and strongly decreases during the fourth decade of life. As we age the daytime secretory pulses diminish first, while the sleep associated GH pulse persists and diminishes gradually.
Nudging Nature
Growth Hormone levels may be increased either by exogenically administering Growth Hormone or by administering Growth Hormone-Releasing Hormone which then endogenically stimulates the somatrope cells of the pituitary to secrete additional Growth Hormone. The primary advantage of GHRH is that GH ends up being released in physiological conformance to the body’s natural biorhythm. This biorhythm is pulsatile.
Studies have concluded that endogenous Growth Hormone Releasing Hormone (GHRH) is the principal regulator of pulsatile GH secretion in humans and that continuous GHRH infusion augments pulsatile GH release. Whereas exogenic administration of GH raises overall GH levels but has no effect on amplifying the pulses.
People of all ages naturally continue to possess the ability to secrete GH from stores within the pituitary. Most studies are in agreement on this point. One study in particular examined the effects of administration of GHRH & a Growth Hormone Releasing Peptide on all adult age groups from those in their 20's to those above 75 years of age. They observed substantial increases in GH release as a direct result of administration of GHRH & GHRP-6. This prompted them to conclude, "...that the lack of side-effects & safety of the protocol and the discovered lack of age-related decline in the 'GHRH-GHRP-6-mediated' GH release opens the possibility of using it as a therapeutical tool to revert some deleterious manifestations of aging in man." (23)
Long-lasting GHRH analog CJC-1295
While the studies have demonstrated repeatedly that administration of GHRH does increase GH secretion and amplifies the release pulse there does remain a significant drawback. GHRH has a very short half life, measured in minutes with a fairly short clearance rate measured in hours. (24) While this is a sufficient amount of time to exert a positive effect on GH secretion, particularly if GHRH is administered multiple times a day, the result is less than optimal. (25,26)
It is for this reason that longer-lasting analogs of GHRH were researched and developed. (28) The most effective of which is CJC-1295.
Exposure of native GHRH to blood plasma results in rapid degradation. CJC-1295, a synthetic human GHRH analog avoids rapid degradation by possessing the ability to selectively and covalently bind to endogenous albumin after subcutaneous administration. Albumin possesses a half-life of 19 days in humans and so modified GHRH bound to albumin greatly extends its half-life and duration of action. (27)
In a recent (2006) study "Prolonged Stimulation of Growth Hormone (GH) and Insulin-Like Growth Factor I Secretion by CJC-1295, a Long-Acting Analog of GH-Releasing Hormone, in Healthy Adults", Sam L. Teichman, et al. Journal of Clinical Endocrinology & Metabolism 91(3):799-805, CJC-1295 was found to result in "sustained, dose-dependent increases in GH and IGF-I levels in healthy adults and was safe and relatively well tolerated, particularly at doses of 30mcg/kg or 60 mcg/kg."
It has been demonstrated repeatedly in various studies that GHRH is effective at instigating GH release and longer acting analogs do increase the overall effectiveness. So it is no surprise that the results of this CJC-1295 study comport with what has been previously demonstrated.
What was unknown was what effect persistent elevation of GH by a long-lasting GHRH analog would have on the pulsatility of release. This was explored in a follow up study, "Pulsatile Secretion of Growth Hormone (GH) Persists during Continuous Stimulation by CJC-1295, a Long- Acting GH-Releasing Hormone Analog", Madalina Ionescu, et al. The Journal of Clinical Endocrinology & Metabolism 91(12):4792-4797.
That study found that pulsatility was not interfered with and was in fact preserved in all subjects both immediately after administration and continuing 7 days post-administration.
This is obviously a very beneficial characteristic to preserve. In fact episodic release appears to be imperative to growth and repair of tissue in mammals.
The study further found that while growth hormone secretion was increased by almost fifty percent there was no increase in pulse amplitude or frequency. All of the increase came from a substantial elevation of trough levels with preserved pulsatility.
One further note of interest is that study participants were all of young age with lower lean body masses which may indicate that GHRH in the form of CJC-1295 is an effective avenue for growth hormone release for those of young age.
The results of the study charted above show that administration of single doses of CJC-1295 resulted in a 2 to10-fold increase in mean serum GH levels in all dosing groups, which was dose incremental and persisted for up to 7 days. Similarly, a dose-related increase in mean serum IGF-I levels was observed at all dose levels, ranging from 1.5- to 3-fold and persisting for up to 14 days. (29)
The results from a toxicology study wherein 50mcg/kg of CJC-1295 was administered subcutaneously to monkeys for a period of six months found no ill effects and no indication of presence of neutralizing antibodies. They concluded that the Drug Affinity Complex (DAC) a technology that enables covalent binding (conjugation) of a drug to albumin produced no evidence of immunogenic or immunotoxic effects in monkeys. (30)
In summary, although the added Drug Affinity Complex adds complexity and increases the expense of CJC-1295 peptide synthesis, it does add tremendously to both the dosing convenience and the biological activity of GHRH without any identifiable adverse toxicity.
References:
1 - Hadden JW, Malec PH, Coto J, Hadden EM 1992 Thymic involution in aging. Prospects for correction. Ann NY Acad Sci 673: 231–239
2 - Mackall CL, Gress RE 1997 Thymic aging and T-cell regeneration. Immunol Rev 160:91–102
3 - Ershler WB, Keller ET 2000 Age-associated increased interleukin-6
gene expression, late-life diseases, and frailty. Annu Rev Med 51:
245–270
4 - van Eekelen JA, Rots NY, Sutanto W, de Kloet ER 1992 The effect of aging on stress responsiveness and central corticosteroid receptors in the brown Norway rat. Neurobiol Aging 13:159–170
5 - Martignoni E, Costa A, Sinforiani E, Liuzzi A, Chiodini P, MauriM, Bono G, Nappi G 1992 The brain as a target for adrenocortical steroids: cognitive implications. Psychoneuroendocrinology 17: 343–354
6 - Liu J, Mori A 1999 Stress, aging, and brain oxidative damage. Neurochem Res 24:1479–1497
7 - Sapolsky R, Armanini M, Packan D, TombaughG1987 Stress and glucocorticoids in aging. Endocrinol Metab Clin North Am 16:965– 980
8 - Heffelfinger AK, Newcomer JW 2001 Glucocorticoid effects on memory function over the human life span. Dev Psychopathol 13:491–513
9 - Murialdo G, Barreca A, Nobili F, Rollero A, Timossi G, Gianelli MV, Copello F, Rodriguez G, Polleri A 2001 Relationships between cortisol, dehydroepiandrosterone sulphate and insulin-like growth factor-I system in dementia. J Endocrinol Invest 24:139–146
10 - Rudman D. Growth hormone, body composition, and aging. J Am Geriatr Soc 1985; 33:800-7.
11 - Meites J. Neuroendocrine biomarkers of aging in the rat. Exp Gerontol 1988; 23:349-58.
12 - Finkelstein JW, Boyar RM, Roffwarg HP, Kream J, Hellman L. Age-related change in the twenty-four-hour spontaneous secretion of growth hormone. J Clin Endocrinol Metab 1972; 35:665-70.
13 - Rudman D, Kutner MH, Rogers CM, Lubin MF, Fleming GA, Bain RP. Impaired growth hormone secretion in the adult population: relation to age and adiposity. J Clin Invest 1981; 67:1361-9.
14 - van Buul-Offers S, Van den Brande JL. The growth of different organs of normal and dwarfed Snell mice, before and during growth hormone therapy. Acta Endocrinol 1981; 96:46-58.
15 - Parra A, Argote RM, Garcia G, Cervantes C, Alatorre S, Perez-Pasten E. Body composition in hypopituitary dwarfs before and during human growth hormone therapy. Metabolism 1979; 28:851-7.
16 - van der Werff ten Bosch JJ, Bot A. Effects of human pituitary growth hormone on body composition. Neth J Med 1987; 30:220-7.
17 - Crist DM, Peake GT, Mackinnon LT, Sibbitt WL Jr, Kraner JC. Exogenous growth hormone treatment alters body composition and increases natural killer cell activity in women with impaired endogenous growth hormone secretion. Metabolism 1987; 36:1115-7.
18 - Jorgensen JOL, Pedersen SA, Thuesen L, et al Beneficial effects of growth hormone treatment in GH-deficient adults. Lancet 1989; 1:1221-5.
19 - Crist DM, Peake GT, Egan PA, Waters DL. Body composition response to exogenous GH during training in highly conditioned adults. J Appl Physiol 1988; 65:579-84.
20 - Salomon F, Cuneo RC, Hesp R, Sonksen PH. The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med 1989; 321:1797- 803.
21 - Jones AJS, O’Connor JV. Chemical characterization of methionyl human growth hormone. In: Hormone drugs: proceedings of the FDA–USP Workshop on Drug and Reference Standards for Insulins, Somatropins, and Thyroid- axis Hormones, Bethesda, Maryland, May 19–21, 1982.
22 - Holl RW, Hartman ML, Veldhuis JD, et al. Thirty-second sampling of plasma growth hormone in man: correlation with sleep stages. J Clin Endocrinol Metab 1991;72:854–61.
23 - Micic D, et al. Preserved Growth Hormone (GH) Secretion in Aged and Very Old Subjects after Testing with the Combined Stimulus GH-Releasing Hormone plus GH-Releasing Hexapeptide-6. J Clin Endocrinol Metab. 1998 Jul;83(7):2569-72
24 - Frohman LA, Downs TR, Williams TC, Heimer EP, Pan YCE, and Felix AM. Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive, N-terminally cleaved product. J Clin Invest 78: 906–913, 1986.
25 - Iordanova VK, Wen SY, Moreau IA, Smith SY, Frohman LA, and Castaigne JP. Every other day subcutaneous administration of CJC-1295, a drug affinity complex (DAC)-growth hormone releasing factor (GRF) analogue, increases body weight and bone mineral content in dogs (Abstract). 87th Annual Meeting of The Endocrine Society, 2005, p. P1–78.
26 - Jette L, Leger R, Thibaudeau K, Benquet C, Robitaille M, Pellerin I, Paradis V, van Wyk P, Pham K, and Bridon DP. Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology 146: 3052–3058, 2005.
27 - Peters JRT. All About Albumin. Biochemistry, Genetics and Medical Applications. San Diego, CA: Academic, 1996.
28 - Hoffman, Andrew R., et al. Efficacy of a Long-Acting Growth Hormone (GH) Preparation in Patients with Adult GH Deficiency. J Clin Endocrinol Metab 90(12):6431–6440
29 - Teichman SL, Neale A, Lawrence B, Cagnon C, Castaigne JP, and Frohman LA. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab 91: 799–805, 2006.
30 – Wen, S. et al. Immunogenicity AND Immunotoxicity Assessments of Two Drug Affinity Complexe Compounds in Cynomogus Monkeys. Toxicologist, Report 170, 2005.
I'm with a lab that has the capability of making 98% pure or above,,note i could save 3grand an order by purchasing 95% but i wouldn't have bragging rights of which I know say I have the strongest cjc1295 available ..only the best will do.
Written by: M.M. a/k/a DatBtrue
Copyright 2008 by M.M. a/k/a DatBtrue
All rights reserved. No part of this article may be reproduced in any form without the written permission of the copyright owner.
Restoring Growth Hormone
"It has been argued that the age-dependent decline in sex steroid, Growth Hormone, and IGF-I production is nature’s way of protecting us from cancer and heart disease, but a far more likely scenario is that once we reach our reproductive capacity, nature begins programming us for death." - Roy G. Smith, Ph.D. Director, Huffington Center on Aging; Professor, Department of Molecular & Cellular Biology; former Vice President for Basic Research at Merck Research Laboratories, Merck & Co
Such programming begins as the second decade of life draws to a close, the negative consequences of which become more noticeable with each passing year.
We begin to experience a steady decline in immune function. (1,2) Our bodies increase production of glucocorticoids (catabolic hormones) and cytokines (inflammatory) which negatively impact metabolism, bone density, strength, exercise tolerance, cognitive function, and mood. (3,4–8)
The hormones of sex, dehydroepiandrosterone (DHEA), Growth Hormone (GH), and Insulin-like Growth Factor (IGF-1) are positively correlated with the health and well-being of the body in general and the specific functioning of metabolism, the cardiovascular system, the musculature skeletal system, cognitive function & the immune system. However these hormonal levels naturally decline as we age and as a consequence those systems necessary to maintain optimal health decline as well. (1-4,9)
"Hence, if we wish to maintain quality of life during aging we must oppose nature." - Roy G. Smith
A progressive decline in lean body mass, atrophy of its component organs & reduction in their function and increased deposition of adipose tissue mass characteristic of the aging human body result partially from the body's diminished secretion of growth hormone. (10-13) These negative changes resulting from growth hormone deficiency have been shown to be reversible by replacement doses of growth hormone. (14-21)
Growth Hormone is a vital anabolic hormone whose positive stimulatory effects on protein synthesis (particularly in the liver, muscle, bone, cartlidge, spleen, kidney, skin, thymus, and red blood cells) and on lipolysis (the breakdown of fat stored in fat cells) contributes greatly to growth, repair & well-being. (10)
Growth Hormone (GH) secretion is primarily regulated by the release of two peptides, Growth Hormone-Releasing Hormone (GHRH) and Somatostatin. The hypothalamus region of the brain releases these hormones in response to signals from the central nervous system. GHRH once released makes its way to the receptors on the somatotrope cells of the pituitary gland of the brain where it stimulates Growth Hormone release. Somatostatin once released makes its way to the receptors on the somatotrope cells of the pituitary gland of the brain where it inhibits Growth Hormone release. (15)
The primary physiological action of somatostatin is to inhibit synthesis and release of GH. (16-19) The primary physiological action of Growth Hormone-Releasing Hormone (GHRH) is to stimulate synthesis and release of GH.
The end product of this cascade, Growth Hormone (GH) once secreted exerts its effect in the body as a whole both directly and indirectly through its initiation of Insulin-like Growth Factor (IGF-1) synthesis in the liver. IGF-1 in turn exerts its effect in the body and its rise in turn begins to inhibit any further GH release.
Growth Hormone (GH) is released periodically within the body in a controlled pulsating fashion. This periodic pattern plays an important role in transmitting the GH "growth, repair & well-being" message to tissue. A review of several studies involving GH replacement in GH-deficient animals reveals the biological significance of episodic secretion. These studies conclude that GH released in a pulsatile pattern is far more efficient in improving mammalian growth and repair than the method of GH administration by constant infusion.
In males GH pulses occur approximately every three (3) hours, a frequency that appears across most mammals. The secretion bursts are preceded and followed by almost undetectable levels of plasma GH.
In females however GH pulses occur more frequently and the base level of plasma GH remains higher than males who have fewer GH pulses but the amplitude of which are more pronounced.
GH pulse amplitudes are increased during slow wave sleep such that particularly in males, most GH secretion occurs at night. (22)
Growth Hormone secretion is highest during the growing years of youth and early adulthood. In humans the secretion rate starts to noticeably decrease during the third decade of life and strongly decreases during the fourth decade of life. As we age the daytime secretory pulses diminish first, while the sleep associated GH pulse persists and diminishes gradually.
Nudging Nature
Growth Hormone levels may be increased either by exogenically administering Growth Hormone or by administering Growth Hormone-Releasing Hormone which then endogenically stimulates the somatrope cells of the pituitary to secrete additional Growth Hormone. The primary advantage of GHRH is that GH ends up being released in physiological conformance to the body’s natural biorhythm. This biorhythm is pulsatile.
Studies have concluded that endogenous Growth Hormone Releasing Hormone (GHRH) is the principal regulator of pulsatile GH secretion in humans and that continuous GHRH infusion augments pulsatile GH release. Whereas exogenic administration of GH raises overall GH levels but has no effect on amplifying the pulses.
People of all ages naturally continue to possess the ability to secrete GH from stores within the pituitary. Most studies are in agreement on this point. One study in particular examined the effects of administration of GHRH & a Growth Hormone Releasing Peptide on all adult age groups from those in their 20's to those above 75 years of age. They observed substantial increases in GH release as a direct result of administration of GHRH & GHRP-6. This prompted them to conclude, "...that the lack of side-effects & safety of the protocol and the discovered lack of age-related decline in the 'GHRH-GHRP-6-mediated' GH release opens the possibility of using it as a therapeutical tool to revert some deleterious manifestations of aging in man." (23)
Long-lasting GHRH analog CJC-1295
While the studies have demonstrated repeatedly that administration of GHRH does increase GH secretion and amplifies the release pulse there does remain a significant drawback. GHRH has a very short half life, measured in minutes with a fairly short clearance rate measured in hours. (24) While this is a sufficient amount of time to exert a positive effect on GH secretion, particularly if GHRH is administered multiple times a day, the result is less than optimal. (25,26)
It is for this reason that longer-lasting analogs of GHRH were researched and developed. (28) The most effective of which is CJC-1295.
Exposure of native GHRH to blood plasma results in rapid degradation. CJC-1295, a synthetic human GHRH analog avoids rapid degradation by possessing the ability to selectively and covalently bind to endogenous albumin after subcutaneous administration. Albumin possesses a half-life of 19 days in humans and so modified GHRH bound to albumin greatly extends its half-life and duration of action. (27)
In a recent (2006) study "Prolonged Stimulation of Growth Hormone (GH) and Insulin-Like Growth Factor I Secretion by CJC-1295, a Long-Acting Analog of GH-Releasing Hormone, in Healthy Adults", Sam L. Teichman, et al. Journal of Clinical Endocrinology & Metabolism 91(3):799-805, CJC-1295 was found to result in "sustained, dose-dependent increases in GH and IGF-I levels in healthy adults and was safe and relatively well tolerated, particularly at doses of 30mcg/kg or 60 mcg/kg."
It has been demonstrated repeatedly in various studies that GHRH is effective at instigating GH release and longer acting analogs do increase the overall effectiveness. So it is no surprise that the results of this CJC-1295 study comport with what has been previously demonstrated.
What was unknown was what effect persistent elevation of GH by a long-lasting GHRH analog would have on the pulsatility of release. This was explored in a follow up study, "Pulsatile Secretion of Growth Hormone (GH) Persists during Continuous Stimulation by CJC-1295, a Long- Acting GH-Releasing Hormone Analog", Madalina Ionescu, et al. The Journal of Clinical Endocrinology & Metabolism 91(12):4792-4797.
That study found that pulsatility was not interfered with and was in fact preserved in all subjects both immediately after administration and continuing 7 days post-administration.
This is obviously a very beneficial characteristic to preserve. In fact episodic release appears to be imperative to growth and repair of tissue in mammals.
The study further found that while growth hormone secretion was increased by almost fifty percent there was no increase in pulse amplitude or frequency. All of the increase came from a substantial elevation of trough levels with preserved pulsatility.
One further note of interest is that study participants were all of young age with lower lean body masses which may indicate that GHRH in the form of CJC-1295 is an effective avenue for growth hormone release for those of young age.
The results of the study charted above show that administration of single doses of CJC-1295 resulted in a 2 to10-fold increase in mean serum GH levels in all dosing groups, which was dose incremental and persisted for up to 7 days. Similarly, a dose-related increase in mean serum IGF-I levels was observed at all dose levels, ranging from 1.5- to 3-fold and persisting for up to 14 days. (29)
The results from a toxicology study wherein 50mcg/kg of CJC-1295 was administered subcutaneously to monkeys for a period of six months found no ill effects and no indication of presence of neutralizing antibodies. They concluded that the Drug Affinity Complex (DAC) a technology that enables covalent binding (conjugation) of a drug to albumin produced no evidence of immunogenic or immunotoxic effects in monkeys. (30)
In summary, although the added Drug Affinity Complex adds complexity and increases the expense of CJC-1295 peptide synthesis, it does add tremendously to both the dosing convenience and the biological activity of GHRH without any identifiable adverse toxicity.
References:
1 - Hadden JW, Malec PH, Coto J, Hadden EM 1992 Thymic involution in aging. Prospects for correction. Ann NY Acad Sci 673: 231–239
2 - Mackall CL, Gress RE 1997 Thymic aging and T-cell regeneration. Immunol Rev 160:91–102
3 - Ershler WB, Keller ET 2000 Age-associated increased interleukin-6
gene expression, late-life diseases, and frailty. Annu Rev Med 51:
245–270
4 - van Eekelen JA, Rots NY, Sutanto W, de Kloet ER 1992 The effect of aging on stress responsiveness and central corticosteroid receptors in the brown Norway rat. Neurobiol Aging 13:159–170
5 - Martignoni E, Costa A, Sinforiani E, Liuzzi A, Chiodini P, MauriM, Bono G, Nappi G 1992 The brain as a target for adrenocortical steroids: cognitive implications. Psychoneuroendocrinology 17: 343–354
6 - Liu J, Mori A 1999 Stress, aging, and brain oxidative damage. Neurochem Res 24:1479–1497
7 - Sapolsky R, Armanini M, Packan D, TombaughG1987 Stress and glucocorticoids in aging. Endocrinol Metab Clin North Am 16:965– 980
8 - Heffelfinger AK, Newcomer JW 2001 Glucocorticoid effects on memory function over the human life span. Dev Psychopathol 13:491–513
9 - Murialdo G, Barreca A, Nobili F, Rollero A, Timossi G, Gianelli MV, Copello F, Rodriguez G, Polleri A 2001 Relationships between cortisol, dehydroepiandrosterone sulphate and insulin-like growth factor-I system in dementia. J Endocrinol Invest 24:139–146
10 - Rudman D. Growth hormone, body composition, and aging. J Am Geriatr Soc 1985; 33:800-7.
11 - Meites J. Neuroendocrine biomarkers of aging in the rat. Exp Gerontol 1988; 23:349-58.
12 - Finkelstein JW, Boyar RM, Roffwarg HP, Kream J, Hellman L. Age-related change in the twenty-four-hour spontaneous secretion of growth hormone. J Clin Endocrinol Metab 1972; 35:665-70.
13 - Rudman D, Kutner MH, Rogers CM, Lubin MF, Fleming GA, Bain RP. Impaired growth hormone secretion in the adult population: relation to age and adiposity. J Clin Invest 1981; 67:1361-9.
14 - van Buul-Offers S, Van den Brande JL. The growth of different organs of normal and dwarfed Snell mice, before and during growth hormone therapy. Acta Endocrinol 1981; 96:46-58.
15 - Parra A, Argote RM, Garcia G, Cervantes C, Alatorre S, Perez-Pasten E. Body composition in hypopituitary dwarfs before and during human growth hormone therapy. Metabolism 1979; 28:851-7.
16 - van der Werff ten Bosch JJ, Bot A. Effects of human pituitary growth hormone on body composition. Neth J Med 1987; 30:220-7.
17 - Crist DM, Peake GT, Mackinnon LT, Sibbitt WL Jr, Kraner JC. Exogenous growth hormone treatment alters body composition and increases natural killer cell activity in women with impaired endogenous growth hormone secretion. Metabolism 1987; 36:1115-7.
18 - Jorgensen JOL, Pedersen SA, Thuesen L, et al Beneficial effects of growth hormone treatment in GH-deficient adults. Lancet 1989; 1:1221-5.
19 - Crist DM, Peake GT, Egan PA, Waters DL. Body composition response to exogenous GH during training in highly conditioned adults. J Appl Physiol 1988; 65:579-84.
20 - Salomon F, Cuneo RC, Hesp R, Sonksen PH. The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med 1989; 321:1797- 803.
21 - Jones AJS, O’Connor JV. Chemical characterization of methionyl human growth hormone. In: Hormone drugs: proceedings of the FDA–USP Workshop on Drug and Reference Standards for Insulins, Somatropins, and Thyroid- axis Hormones, Bethesda, Maryland, May 19–21, 1982.
22 - Holl RW, Hartman ML, Veldhuis JD, et al. Thirty-second sampling of plasma growth hormone in man: correlation with sleep stages. J Clin Endocrinol Metab 1991;72:854–61.
23 - Micic D, et al. Preserved Growth Hormone (GH) Secretion in Aged and Very Old Subjects after Testing with the Combined Stimulus GH-Releasing Hormone plus GH-Releasing Hexapeptide-6. J Clin Endocrinol Metab. 1998 Jul;83(7):2569-72
24 - Frohman LA, Downs TR, Williams TC, Heimer EP, Pan YCE, and Felix AM. Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive, N-terminally cleaved product. J Clin Invest 78: 906–913, 1986.
25 - Iordanova VK, Wen SY, Moreau IA, Smith SY, Frohman LA, and Castaigne JP. Every other day subcutaneous administration of CJC-1295, a drug affinity complex (DAC)-growth hormone releasing factor (GRF) analogue, increases body weight and bone mineral content in dogs (Abstract). 87th Annual Meeting of The Endocrine Society, 2005, p. P1–78.
26 - Jette L, Leger R, Thibaudeau K, Benquet C, Robitaille M, Pellerin I, Paradis V, van Wyk P, Pham K, and Bridon DP. Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology 146: 3052–3058, 2005.
27 - Peters JRT. All About Albumin. Biochemistry, Genetics and Medical Applications. San Diego, CA: Academic, 1996.
28 - Hoffman, Andrew R., et al. Efficacy of a Long-Acting Growth Hormone (GH) Preparation in Patients with Adult GH Deficiency. J Clin Endocrinol Metab 90(12):6431–6440
29 - Teichman SL, Neale A, Lawrence B, Cagnon C, Castaigne JP, and Frohman LA. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab 91: 799–805, 2006.
30 – Wen, S. et al. Immunogenicity AND Immunotoxicity Assessments of Two Drug Affinity Complexe Compounds in Cynomogus Monkeys. Toxicologist, Report 170, 2005.
