Growth hormone

From Wikipedia, the free encyclopedia

Jump to: navigation, search

"HGH" redirects here. For other uses, see HGH (disambiguation).

Growth hormone 1

Growth hormone
Identifiers
Symbol

GH1

Entrez

2688

HUGO

4261

OMIM

139250

RefSeq

NM_022562

UniProt

P01241
Other data

Locus

Chr. 17 q22-q24

Growth hormone 2
Identifiers
Symbol

GH2

Entrez

2689

HUGO

4262

OMIM

139240

RefSeq

NM_002059

UniProt

P01242
Other data

Locus

Chr. 17 q22-q24

Growth hormone (GH) is a protein-based peptide hormone. It stimulates growth, cell

reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino
acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells
within the lateral wings of the anterior pituitary gland. Somatotropin refers to the growth
hormone 1 produced naturally in animals, whereas the term somatropin refers to growth
hormone produced by recombinant DNA technology,[1] and is abbreviated "HGH" in humans.
Growth hormone is used as a prescription drug in medicine to treat children's growth disorders
and adult growth hormone deficiency. In the United States, it is only available legally from
pharmacies, by prescription from a doctor. In recent years in the United States, some doctors
have started to prescribe growth hormone in GH-deficient older patients (but not on healthy
people) to increase vitality. While legal, the efficacy and safety of this use for HGH has not been
tested in a clinical trial. At this time, HGH is still considered a very complex hormone, and many
of its functions are still unknown.[2]
In its role as an anabolic agent, HGH has been abused by competitors in sports since the 1970s,
and it has been banned by the IOC and NCAA. Traditional urine analysis could not detect doping
with HGH, so the ban was unenforceable until the early 2000s when blood tests that could
distinguish between natural and artificial HGH were starting to be developed. Blood tests
conducted by WADA at the 2004 Olympic Games in Athens, Greece targeted primarily HGH.[2]

This use for the drug is not approved by the FDA; GH is legally available only by prescription in
the United States.
GH has been studied for use in raising livestock more efficiently in industrial agriculture and
several efforts have been made to obtain governmental approval to use GH in livestock
production. These uses have been controversial. In the United States, the only FDA-approved use
of GH is the use of a cow-specific form of GH called bovine somatotropin for increasing milk
production in dairy cows. Now retailers are permitted to label containers of milk as produced
with or without bovine somatotropin.

Contents

1 Biology
o

1.1 Gene locus

1.2 Structure

1.3 Biological regulation

1.4 Normal functions of GH produced by the body

1.5 Problems caused when the body produces too much GH

1.6 Problems caused when the body produces too little GH

2 GH in human medicine
o

2.1 FDA-approved treatments with GH related to deficiency of GH

2.2 FDA-approved treatments with GH unrelated to deficiency of GH

2.3 Experimental uses

2.4 Side-effects

3 Non-medical use in athletic enhancement

4 Use of GH in production of meat and milk

5 History of use and manufacture of GH as a drug

6 Dietary supplements claiming relation to GH

7 References

[edit] Biology
[edit] Gene locus
Main articles: Growth hormone 1 and Growth hormone 2
Genes for human growth hormone, known as growth hormone 1 (somatotropin) and growth
hormone 2, are localized in the q22-24 region of chromosome 17[3][4] and are closely related to
human chorionic somatomammotropin (also known as placental lactogen) genes. GH, human
chorionic somatomammotropin, and prolactin belong to a group of homologous hormones with
growth-promoting and lactogenic activity.

[edit] Structure
The major isoform of the human growth hormone is a protein of 191 amino acids and a
molecular weight of 22,124 daltons. The structure includes four helices necessary for functional
interaction with the GH receptor. It appears that, in structure, GH is evolutionarily homologous
to prolactin and chorionic somatomammotropin. Despite marked structural similarities between
growth hormone from different species, only human and primate growth hormones have
significant effects in humans.
Several molecular isoforms of GH exist in the pituitary gland and are released to blood. In
particular, a variant of approximately 20 kDa originated by an alternative splicing is present in a
rather constant 1:9 ratio,[5] while recently an additional variant of ~ 23-24 kDa has also been
reported in post-exercise states at higher proportions.[6] This variant has not been identified, but it
has been suggested to coincide with a 22 kDa glycosilated variant of 23 kDa identified in the
pituitary gland.[7] Furthermore, these variants circulate partially bound to a protein (growth
hormone-binding protein, GHBP), which is the truncated part of the growth hormone receptor,
and an acid-labile subunit (ALS).

[edit] Biological regulation

Peptides released by neurosecretory nuclei of the hypothalamus (Growth hormone-releasing
hormone/somatocrinin and Growth hormone-inhibiting hormone/somatostatin) into the
hypophyseal portal venous blood surrounding the pituitary are the major controllers of GH
secretion by the somatotropes. However, although the balance of these stimulating and inhibiting
peptides determines GH release, this balance is affected by many physiological stimulators (e.g.,
exercise, nutrition, sleep) and inhibitors of GH secretion (e.g., Free fatty acids)[8] Stimulators of
HGH secretion include:

peptide hormones
o
o

Growth hormone-releasing hormone (GHRH) through binding to the growth

hormone-releasing hormone receptor (GHRHR)[9]
ghrelin through binding to growth hormone secretagogue receptors (GHSR)[10]
sex hormones[11]

o
o

increased androgen secretion during puberty (in males from testis and in females
from adrenal cortex)
estrogen

clonidine and L-DOPA by stimulating GHRH release[12]

hypoglycemia, arginine[13] and propranolol by inhibiting somatostatin release[12]

deep sleep[14]

fasting[15]

vigorous exercise [16]

Inhibitors of GH secretion include:

somatostatin from the periventricular nucleus [17]

circulating concentrations of GH and IGF-1 (negative feedback on the pituitary and
hypothalamus)[2]

hyperglycemia[12]

glucocorticoids[18]

dihydrotestosterone

In addition to control by endogenous and stimulus processes, a number of foreign compounds

(xenobiotics such as drugs and endocrine disruptors) are known to influence GH secretion and
function.[19]
HGH is synthesized and secreted from the anterior pituitary gland in a pulsatile manner
throughout the day; surges of secretion occur at 3- to 5-hour intervals.[2] The plasma
concentration of GH during these peaks may range from 5 to even 45 ng/mL.[20] The largest and

most predictable of these GH peaks occurs about an hour after onset of sleep.[21] Otherwise there
is wide variation between days and individuals. Nearly fifty percent of HGH secretion occurs
during the third and fourth NREM sleep stages.[22] Between the peaks, basal GH levels are low,
usually less than 5 ng/mL for most of the day and night.[21] Additional analysis of the pulsatile
profile of GH described in all cases less than 1 ng/ml for basal levels while maximum peaks
were situated around 10-20 ng/mL.[23][24]
A number of factors are known to affect HGH secretion, such as age, gender, diet, exercise,
stress, and other hormones.[2] Young adolescents secrete HGH at the rate of about 700 g/day,
while healthy adults secrete HGH at the rate of about 400 g/day.[25]

[edit] Normal functions of GH produced by the body

Main pathways in endocrine regulation of growth.
Effects of growth hormone on the tissues of the body can generally be described as anabolic
(building up). Like most other protein hormones, GH acts by interacting with a specific receptor
on the surface of cells.
Increased height during childhood is the most widely known effect of GH. Height appears to be
stimulated by at least two mechanisms:
1. Because polypeptide hormones are not fat-soluble, they cannot penetrate sarcolemma.
Thus, GH exerts some of its effects by binding to receptors on target cells, where it
activates the MAPK/ERK pathway.[26] Through this mechanism GH directly stimulates
division and multiplication of chondrocytes of cartilage.
2. GH also stimulates, through the JAK-STAT signaling pathway,[26] the production of
insulin-like growth factor 1 (IGF-1, formerly known as somatomedin C), a hormone
homologous to proinsulin.[27] The liver is a major target organ of GH for this process and
is the principal site of IGF-1 production. IGF-1 has growth-stimulating effects on a wide
variety of tissues. Additional IGF-1 is generated within target tissues, making it what
appears to be both an endocrine and an autocrine/paracrine hormone. IGF-1 also has
stimulatory effects on osteoblast and chondrocyte activity to promote bone growth.
In addition to increasing height in children and adolescents, growth hormone has many other
effects on the body:

Increases calcium retention, and strengthens and increases the mineralization of bone

Increases muscle mass through sarcomere hyperplasia

Promotes lipolysis

Increases protein synthesis

Stimulates the growth of all internal organs excluding the brain

Plays a role in homeostasis

Reduces liver uptake of glucose

Promotes gluconeogenesis in the liver[28]

Contributes to the maintenance and function of pancreatic islets

Stimulates the immune system

[edit] Problems caused when the body produces too much GH

The most common disease of GH excess is a pituitary tumor composed of somatotroph cells of
the anterior pituitary. These somatotroph adenomas are benign and grow slowly, gradually
producing more and more GH. For years, the principal clinical problems are those of GH excess.
Eventually, the adenoma may become large enough to cause headaches, impair vision by
pressure on the optic nerves, or cause deficiency of other pituitary hormones by displacement.
Prolonged GH excess thickens the bones of the jaw, fingers and toes. Resulting heaviness of the
jaw and increased size of digits is referred to as acromegaly. Accompanying problems can
include sweating, pressure on nerves (e.g., carpal tunnel syndrome), muscle weakness, excess
sex hormone-binding globulin (SHBG), insulin resistance or even a rare form of type 2 diabetes,
and reduced sexual function.
GH-secreting tumors are typically recognized in the fifth decade of life. It is extremely rare for
such a tumor to occur in childhood, but, when it does, the excessive GH can cause excessive
growth, traditionally referred to as pituitary gigantism.
Surgical removal is the usual treatment for GH-producing tumors. In some circumstances,
focused radiation or a GH antagonist such as pegvisomant may be employed to shrink the tumor
or block function. Other drugs like octreotide (somatostatin agonist) and bromocriptine
(dopamine agonist) can be used to block GH secretion because both somatostatin and dopamine
negatively inhibit GHRH-mediated GH release from the anterior pituitary.

[edit] Problems caused when the body produces too little GH

Main article: Growth hormone deficiency
The effects of growth hormone deficiency vary depending on the age at which they occur. In
children, growth failure and short stature are the major manifestations of GH deficiency, with
common causes including genetic conditions and congenital malformations. It can also cause
delayed sexual maturity. In adults, deficiency is rare,[29] with the most common cause a pituitary

adenoma, and others including a continuation of a childhood problem, other structural lesions or
trauma, and very rarely idiopathic GHD.
Adults with GHD present with non-specific problems including truncal obesity with a relative
decrease in muscle mass and, in many instances, decreased energy and quality of life.[29]
Diagnosis of GH deficiency involves a multiple-step diagnostic process, usually culminating in
GH stimulation tests to see if the patient's pituitary gland will release a pulse of GH when
provoked by various stimuli.

[edit] GH in human medicine

Main article: Growth hormone treatment
See sections above for problems caused when the body produces too much GH or too little GH.

[edit] FDA-approved treatments with GH related to deficiency of GH

Treatment with exogenous GH is indicated only in limited circumstances,[29] and needs regular
monitoring due to the frequency and severity of side-effects. GH is used as replacement therapy
in adults with GH deficiency of either childhood-onset (after completing growth phase) or adultonset (usually as a result of an acquired pituitary tumor). In these patients, benefits have variably
included reduced fat mass, increased lean mass, increased bone density, improved lipid profile,
reduced cardiovascular risk factors, and improved psychosocial well-being.

[edit] FDA-approved treatments with GH unrelated to deficiency of GH

GH can be used to treat conditions that produce short stature but are not related to deficiencies in
GH. However, results are not as dramatic when compared to short stature that is solely
attributable to deficiency of GH. Examples of other causes of shortness often treated with GH are
Turner syndrome, chronic renal failure, PraderWilli syndrome, intrauterine growth retardation,
and severe idiopathic short stature. Higher ("pharmacologic") doses are required to produce
significant acceleration of growth in these conditions, producing blood levels well above normal
("physiologic"). Despite the higher doses, side-effects during treatment are rare, and vary little
according to the condition being treated.

[edit] Experimental uses

The following discussion describes experimental uses of GH, that are legal when the GH is
prescribed by a doctor. However, the efficacy and safety of use of GH as anti-aging agent are
unknown as this use has not been tested in a double-blinded clinical trial.
In recent years in the United States, some doctors have started to prescribe growth hormone in
GH-deficient older patients (but not on healthy people) to increase vitality. While legal, the

efficacy and safety of this use for HGH has not been tested in a clinical trial. At this time, hGH is
still considered a very complex hormone, and many of its functions are still unknown.[2]
Claims for GH as an anti-aging treatment date back to 1990 when the New England Journal of
Medicine published a study wherein GH was used to treat 12 men over 60.[30] At the conclusion
of the study, all the men showed statistically significant increases in lean body mass and bone
mineral, while the control group did not. The authors of the study noted that these improvements
were the opposite of the changes that would normally occur over a 10- to 20-year aging period.
Despite the fact the authors at no time claimed that GH had reversed the aging process itself,
their results were misinterpreted as indicating that GH is an effective anti-aging agent.[31][32][33]
This has led to organizations such as the controversial American Academy of Anti-Aging
Medicine promoting the use of this hormone as an "anti-aging agent".[34]
A Stanford University School of Medicine survey of clinical studies on the subject published in
early 2007 showed that the application of GH on healthy elderly patients increased muscle by
about 2 kg and decreased body fat by the same amount.[31] However, these were the only positive
effects from taking GH. No other critical factors were affected, such as bone density, cholesterol
levels, lipid measurements, maximal oxygen consumption, or any other factor that would
indicate increased fitness.[31] Researchers also did not discover any gain in muscle strength,
which led them to believe that GH merely let the body store more water in the muscles rather
than increase muscle growth. This would explain the increase in lean body mass.
GH has also been used experimentally to treat multiple sclerosis, to enhance weight loss in
obesity, as well as in fibromyalgia, heart failure, Crohn's disease and ulcerative colitis, and
burns. GH has also been used in maintaining muscle mass in wasting due to AIDS and in patients
with short bowel syndrome to lessen the requirement for intravenous total parenteral nutrition.

[edit] Side-effects
Use of GH as a drug has been approved by the FDA for several indications. This means that the
drug has acceptable safety in light of its benefits when used in the approved way. Like every
drug, there are several side effects caused by GH, some common, some rare. Injection-site
reaction is common. More rarely, patients can experience joint swelling, joint pain, carpal tunnel
syndrome, and an increased risk of diabetes.[31] In some cases, the patient can produce an
immune response against GH. GH may also be a risk factor for Hodgkin's lymphoma.[35]
One survey of adults that had been treated with replacement cadaver GH (which has not been
used anywhere in the world since 1985) during childhood showed a mildly increased incidence
of colon cancer and prostate cancer, but linkage with the GH treatment was not established.[36]

[edit] Non-medical use in athletic enhancement

Main article: Growth hormone in sports
Athletes in many sports have used human growth hormone in order to attempt to enhance their
athletic performance. Some recent studies have not been able to support claims that human

growth hormone can improve the athletic performance of professional male athletes.[37][38][39]
Many athletic societies ban the use of GH and will issue sanctions against athletes who are
caught using it. In the United States, GH is legally available only by prescription from a medical
doctor.

[edit] Use of GH in production of meat and milk

In the United States, it is legal to give a bovine GH to dairy cows to increase milk production,
but it is not legal to use GH in raising cows for beef; see articles on Bovine somatotropin and
cattle feeding and dairy farming and Beef hormone controversy.
Use in poultry farming is illegal in the United States as per the poultry farming article.
Several companies have attempted to have a version of GH for use in pigs (porcine
somatotropin) approved by the FDA but all applications have been withdrawn.[40][41]

[edit] History of use and manufacture of GH as a drug

Main article: Growth hormone treatment#History
The identification, purification and later synthesis of growth hormone is associated with Choh
Hao Li. Genentech pioneered the first use of recombinant human growth hormone for human
therapy in 1981.
Prior to its production by recombinant DNA technology, growth hormone used to treat
deficiencies was extracted from the pituitary glands of cadavers. Attempts to create a wholly
synthetic HGH failed. Limited supplies of HGH resulted in the restriction of HGH therapy to the
treatment of idiopathic short stature.[42] Furthermore, growth hormone from other primates was
found to be inactive in humans.[43]
In 1985, unusual cases of Creutzfeldt-Jacob disease were found in individuals that had received
cadaver-derived HGH ten to fifteen years previously. Based on the assumption that infectious
prions causing the disease were transferred along with the cadaver-derived HGH, cadaverderived HGH was removed from the market.[25]
In 1985, biosynthetic human growth hormone replaced pituitary-derived human growth hormone
for therapeutic use in the U.S. and elsewhere.
As of 2005, recombinant growth hormones available in the United States (and their
manufacturers) included Nutropin (Genentech), Humatrope (Lilly), Genotropin (Pfizer),
Norditropin (Novo), and Saizen (Merck Serono). In 2006, the U.S. Food and Drug
Administration (FDA) approved a version of rHGH called Omnitrope (Sandoz). A sustainedrelease form of growth hormone, Nutropin Depot (Genentech and Alkermes) was approved by
the FDA in 1999, allowing for fewer injections (every 2 or 4 weeks instead of daily); however,

the product was discontinued by Genentech/Alkermes in 2004 for financial reasons (Nutropin
Depot required significantly more resources to produce than the rest of the Nutropin line[44]).

[edit] Dietary supplements claiming relation to GH

To capitalize on the idea that GH can be used to combat aging has entered American culture,
companies selling dietary supplements have websites selling products linked to GH in the
advertising text, with medical-sounding names described as "HGH Releasers". Typical
ingredients include amino acids, minerals, vitamins, and/or herbal extracts, the combination of
which are described as causing the body to make more GH with corresponding beneficial effects.
In the United States, because these products are marketed as dietary supplements it is illegal for
them to contain GH, which is a drug. Also, under United States law, products sold as dietary
supplements cannot have claims that the supplement treats or prevents any disease or condition,
and the advertising material must contain a statement that the health claims are not approved by
the FDA. The FTC and the FDA do enforce the law when they become aware of violations.[45]

[edit] References
1.

^ Daniels ME (1992). "Lilly's Humatrope Experience". Nature Biotechnology 10 (7): 812.

doi:10.1038/nbt0792-812a.

2.

^ a b c d e f Powers M (2005). "Performance-Enhancing Drugs". In Deidre Leaver-Dunn; Joel

Houglum; Harrelson, Gary L.. Principles of Pharmacology for Athletic Trainers. Slack Incorporated.
pp. 331332. ISBN 1-55642-594-5.

3.

^ "GH1 growth hormone 1 (Homo sapiens) - Gene". National Center for Biotechnology
Information, U.S. National Library of Medicine. http://www.ncbi.nlm.nih.gov/gene/2688.

4.

^ "GH2 growth hormone 2 (Homo sapiens) - Gene". National Center for Biotechnology
Information, U.S. National Library of Medicine. http://www.ncbi.nlm.nih.gov/gene/2689.

5.

^ Leung KC, Howe C, Gui LY, Trout G, Veldhuis JD, Ho KK (October 2002). "Physiological and
pharmacological regulation of 20-kDa growth hormone". Am. J. Physiol. Endocrinol. Metab. 283 (4):
E83643. doi:10.1152/ajpendo.00122.2002. PMID 12217902.

6.

^ Kohler M, Pschel K, Sakharov D, Tonevitskiy A, Schnzer W, Thevis M (November 2008).

"Detection of recombinant growth hormone in human plasma by a 2-D PAGE method". Electrophoresis 29
(22): 4495502. doi:10.1002/elps.200800221. PMID 19003817.

7.

^ Bustamante JJ, Gonzalez L, Carroll CA, Weintraub ST, Aguilar RM, Muoz J, Martinez AO,
Haro LS (July 2009). "O-Glycosylated 24-kDa human growth hormone (hGH) has a mucin-like
biantennary disialylated tetrasaccharide attached at Thr-60". Proteomics 9 (13): 347488.
doi:10.1002/pmic.200800989. PMC 2904392. PMID 19579232.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2904392.

8.

^ Bartholomew, Edwin F.; Martini, Frederic; Judi Lindsley Nath (2009). Fundamentals of
anatomy & physiology. Upper Saddle River, NJ: Pearson Education Inc. pp. 616617. ISBN 0-321-539109.

9.

^ Lin-Su K, Wajnrajch MP (December 2002). "Growth Hormone Releasing Hormone (GHRH)

and the GHRH Receptor". Rev Endocr Metab Disord 3 (4): 31323. doi:10.1023/A:1020949507265.
PMID 12424433.

10.

^ Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, Kennedy AR, Roberts GH,
Morgan DG, Ghatei MA, Bloom SR (November 2000). "The novel hypothalamic peptide ghrelin stimulates
food intake and growth hormone secretion". Endocrinology 141 (11): 43258. doi:10.1210/en.141.11.4325.
PMID 11089570.

11.

^ Meinhardt UJ, Ho KK (October 2006). "Modulation of growth hormone action by sex steroids".
Clin. Endocrinol. (Oxf) 65 (4): 41322. doi:10.1111/j.1365-2265.2006.02676.x. PMID 16984231.

12.

^ a b c Low LC (1991). "Growth hormone-releasing hormone: clinical studies and therapeutic

aspects". Neuroendocrinology 53 Suppl 1: 3740. PMID 1901390.

13.

^ Alba-Roth J, Mller OA, Schopohl J, von Werder K (December 1988). "Arginine stimulates
growth hormone secretion by suppressing endogenous somatostatin secretion". J. Clin. Endocrinol. Metab.
67 (6): 11869. doi:10.1210/jcem-67-6-1186. PMID 2903866.

14.

^ Van Cauter E, Latta F, Nedeltcheva A, Spiegel K, Leproult R, Vandenbril C, Weiss R, Mockel J,

Legros JJ, Copinschi G (June 2004). "Reciprocal interactions between the GH axis and sleep". Growth
Horm. IGF Res. 14 Suppl A: S107. doi:10.1016/j.ghir.2004.03.006. PMID 15135771.

15.

^ Nrrelund H (April 2005). "The metabolic role of growth hormone in humans with particular
reference to fasting". Growth Horm. IGF Res. 15 (2): 95122. doi:10.1016/j.ghir.2005.02.005.
PMID 15809014.

16.

^ Kanaley JA, Weltman JY, Veldhuis JD, Rogol AD, Hartman ML, Weltman A (November 1997).
"Human growth hormone response to repeated bouts of aerobic exercise". J. Appl. Physiol. 83 (5): 1756
61. PMID 9375348. http://jap.physiology.org/cgi/content/full/83/5/1756.

17.

^ Guillemin R, Gerich JE (1976). "Somatostatin: physiological and clinical significance". Annu.

Rev. Med. 27: 37988. doi:10.1146/annurev.me.27.020176.002115. PMID 779605.

18.

^ Allen DB (September 1996). "Growth suppression by glucocorticoid therapy". Endocrinol.

Metab. Clin. North Am. 25 (3): 699717. doi:10.1016/S0889-8529(05)70348-0. PMID 8879994.

19.

^ Scarth JP (2006). "Modulation of the growth hormone-insulin-like growth factor (GH-IGF) axis
by pharmaceutical, nutraceutical and environmental xenobiotics: an emerging role for xenobioticmetabolizing enzymes and the transcription factors regulating their expression. A review". Xenobiotica 36
(23): 119218. doi:10.1080/00498250600621627. PMID 16702112.

20.

^ Natelson BH, Holaday J, Meyerhoff J, Stokes PE (August 1975). "Temporal changes in growth
hormone, cortisol, and glucose: relation to light onset and behavior". Am. J. Physiol. 229 (2): 40915.
PMID 808970. http://ajplegacy.physiology.org/cgi/content/abstract/229/2/409.

21.

^ a b Takahashi Y, Kipnis D, Daughaday W (1968). "Growth hormone secretion during sleep". J

Clin Invest 47 (9): 207990. doi:10.1172/JCI105893. PMC 297368. PMID 5675428.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=297368.

22.

^ Mehta Ameeta, Hindmarsh Peter (2002). "The use of somatropin (recombinant growth hormone)
in children of short stature". Pediatric Drugs 4 (1): 3747. PMID 11817985.

23.

^ Nindl BC, Hymer WC, Deaver DR, Kraemer WJ (1 July 2001). "Growth hormone pulsatility
profile characteristics following acute heavy resistance exercise". J. Appl. Physiol. 91 (1): 16372.
PMID 11408427. http://jap.physiology.org/cgi/content/abstract/91/1/163.

24.

^ Juul A, Jrgensen JO, Christiansen JS, Mller J, Skakkeboek NE (1995). "Metabolic effects of
GH: a rationale for continued GH treatment of GH-deficient adults after cessation of linear growth". Horm.
Res. 44 Suppl 3 (3): 6472. doi:10.1159/000184676. PMID 8719443.

25.

^ a b Gardner, David G., Shoback, Dolores (2007). Greenspan's Basic and Clinical Endocrinology
(8th ed.). New York: McGraw-Hill Medical. pp. 193201. ISBN 0-07-144011-9.

26.

^ a b Binder G, Wittekindt N, Ranke MB (February 2007). "Noonan Syndrome: Genetics and

Responsiveness to Growth Hormone Therapy". Horm Res 67 (Supplement 1): 4549.
doi:10.1159/000097552. ISBN 9783805582551. http://books.google.com/?
id=nQ9ilbixQEgC&pg=PA46&lpg=PA46&dq=gh+growth+hormone+ras&q=gh%20growth%20hormone
%20ras.

27.

^ "Actions of Anterior Pituitary Hormones: Physiologic Actions of GH". Medical College of

Georgia. 2007. http://www.lib.mcg.edu/edu/eshuphysio/program/section5/5ch2/s5ch2_19.htm. Retrieved
2008-01-16.

28.

^ King, MW (2006). "Structure and Function of Hormones: Growth Hormone". Indiana State
University. http://web.indstate.edu/thcme/mwking/peptide-hormones.html#gh. Retrieved 2008-01-16.

29.

^ a b c Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Shalet SM, Vance ML; Endocrine
Society's Clinical Guidelines Subcommittee, Stephens PA (May 2006). "Evaluation and treatment of adult
growth hormone deficiency: an Endocrine Society Clinical Practice Guideline". J. Clin. Endocrino. Metab.
91 (5): 162134. doi:10.1210/jc.2005-2227. PMID 16636129.

30.

^ Rudman D, Feller AG, Nagraj HS, Gergans GA, Lalitha PY, Goldberg AF, Schlenker RA, Cohn
L, Rudman IW, Mattson DE (July 1990). "Effects of human growth hormone in men over 60 years old". N.
Engl. J. Med. 323 (1): 16. doi:10.1056/NEJM199007053230101. PMID 2355952.

31.

^ a b c d Liu H, Bravata DM, Olkin I, Nayak S, Roberts B, Garber AM, Hoffman AR (January
2007). "Systematic review: the safety and efficacy of growth hormone in the healthy elderly". Ann. Intern.
Med. 146 (2): 10415. PMID 17227934.

32.

^ "No proof that growth hormone therapy makes you live longer, study finds". PhysOrg.com.
2007-01-16. http://www.physorg.com/news88140162.html. Retrieved 2009-03-16.

33.
34.

35.
36.

^ Stephen Barrett, M.D. Growth Hormone Schemes and Scams

^ Kuczynski, Alex (1998-04-12). "Anti-Aging Potion or Poison?". New York Times.
http://www.nytimes.com/1998/04/12/style/anti-aging-potion-or-poison.html.
^ http://www.jstage.jst.go.jp/article/endocrj/52/5/52_571/_article
^ Swerdlow AJ, Higgins CD, Adlard P, Preece MA (July 2002). "Risk of cancer in patients treated
with human pituitary growth hormone in the UK, 1959-85: a cohort study". Lancet 360 (9329): 2737.
doi:10.1016/S0140-6736(02)09519-3. PMID 12147369.

37.

^ Liu H, Bravata DM, Olkin I, Friedlander A, Liu V, Roberts B, Bendavid E, Saynina O, Salpeter
SR, Garber AM, Hoffman AR (May 2008). "Systematic review: the effects of growth hormone on athletic
performance". Ann. Intern. Med. 148 (10): 74758. PMID 18347346.

38.

^ Randall T (2008-03-17). "Athletes Don't Benefit From Human Growth Hormone, Study Finds".
Bloomberg. http://www.bloomberg.com/apps/news?pid=newsarchive&sid=awlswGxIiU5c&refer=home.
Retrieved 2011-08-28.

39.

^ Gaffney G (2008-03-17). "Steroid Nation: Review from Stanford says HGH no benefit as PED".
Steroid Nation. http://grg51.typepad.com/steroid_nation/2008/03/review-from-sta.html. Retrieved 2011-0828.

40.

^ "Center for Veterinary Medicine Master" (pdf). www.fda.gov. 2011-04-06.

http://www.fda.gov/downloads/AnimalVeterinary/DevelopmentApprovalProcess/UCM071853.pdf.
Retrieved 2011-08-28.

41.

^ "Growth Promoters in Animal Production" (pdf). 2006.

http://www.lemars.k12.ia.us/ag/AgriScience%202%20class/Animal%20Nutrition%20Unit/Growth
%20promoters%20in%20AS.pdf. Retrieved 2011-08-28.

42.

^ Maybe, Nancy G (1984). "Direct expression of human growth in Escherichia coli with the
lipoprotein promoter". In Arthur P. Bollon. Recombinant DNA products: insulin, interferon, and growth
hormone. Boca Raton: CRC Press. ISBN 0-8493-5542-7.

43.

^ Hintz, Raymond L. (1984). "Biological actions in humans of recombinant DNA synthesized

human growth hormone". In Arthur P. Bollon. Recombinant DNA products: insulin, interferon, and growth
hormone. Boca Raton: CRC Press. ISBN 0-8493-5542-7.

44.

^ "Genentech and Alkermes Announce Decision to Discontinue Commercialization of Nutropin

Depot". Press Release. Business Wire. 2004-06-01.
http://findarticles.com/p/articles/mi_m0EIN/is_2004_June_1/ai_n6050768. Retrieved 2011-08-28.

45.

^ Singleton ER (2010-06-04). "Atlas Operations, Inc.". Warning Letter. U.S. Food and Drug
Administration. http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm215918.htm.
Retrieved 2011-08-28.