Growth hormone: Difference between revisions

Several [[molecule|molecular]] isoforms of GH exist in the pituitary gland and are released to blood. In particular, a ~ 20 kDa variant originated by an alternative splicing is present in a rather constant 1:9 ratio,<ref name="pmid12217902">{{cite journal | author = Leung KC, Howe C, Gui LY, Trout G, Veldhuis JD, Ho KK | title = Physiological and pharmacological regulation of 20-kDa growth hormone | journal = Am. J. Physiol. Endocrinol. Metab. | volume = 283 | issue = 4 | pages = E836–43 | year = 2002 | month = October | pmid = 12217902 | doi = 10.1152/ajpendo.00122.2002 | url = | issn = }}</ref> while recently an additional variant of ~ 23-24 kDa has also been reported in post-exercise states at higher proportions.<ref name="pmid19003817">{{cite journal | author = Kohler M, Püschel K, Sakharov D, Tonevitskiy A, Schänzer W, Thevis M | title = Detection of recombinant growth hormone in human plasma by a 2-D PAGE method | journal = Electrophoresis | volume = 29 | issue = 22 | pages = 4495–502 | year = 2008 | month = November | pmid = 19003817 | doi = 10.1002/elps.200800221 | url = | issn = }}</ref> 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.<ref name="pmid19579232">{{cite journal | author = Bustamante JJ, Gonzalez L, Carroll CA, Weintraub ST, Aguilar RM, Muñoz J, Martinez AO, Haro LS | title = O-Glycosylated 24 kDa human growth hormone has a mucin-like biantennary disialylated tetrasaccharide attached at Thr-60 | journal = Proteomics | volume = 9 | issue = 13 | pages = 3474–88 | year = 2009 | month = July | pmid = 19579232 | pmc = 2904392 | doi = 10.1002/pmic.200800989 | url = | issn = }}</ref> 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).

 

Peptides released by neurosecretory nuclei of the [[hypothalamus]] (Growth hormone-releasing hormone/''somatocrinin'' and Growth hormone-inhibiting hormone/''somatostatin'') into the [[hypophyseal portal system|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)<ref name="isbn0-321-53910-9">{{cite book | author = Bartholomew, Edwin F.; Martini, Frederic; Judi Lindsley Nath | authorlink = | editor = | others = | title = Fundamentals of anatomy & physiology | edition = | language = | publisher = Pearson Education Inc | location = Upper Saddle River, NJ | year = 2009 | origyear = | pages = 616–617 | quote = | isbn = 0-321-53910-9 | oclc = | doi = | url = | accessdate = }}</ref>

''Stimulators'' of HGH secretion include:

A number of factors are known to affect HGH secretion, such as age, gender, diet, exercise, stress, and other hormones.<ref name=ped/> Young adolescents secrete HGH at the rate of about 700 μg/day, while healthy adults secrete HGH at the rate of about 400 μg/day.<ref name = "isbn0-07-144011-9" >{{cite book | author = Gardner, David G., Shoback, Dolores | title = Greenspan's Basic and Clinical Endocrinology | edition = 8th |series= | year = 2007 | publisher= McGraw-Hill Medical | location = New York | isbn = 0-07-144011-9 |oclc= | pages = 193–201 | chapter = | chapterurl = | quote = }}</ref>

 

[[File:Endocrine growth regulation.svg|thumb|240px|Main pathways in endocrine regulation of growth.]]

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.

 

{{Main|Growth hormone treatment}}

 

See sections above for problems caused when the body produces too much GH or too little GH.

 

 

Treatment with exogenous GH is indicated only in limited circumstances,<ref name="Molitch et al. 2006"/> 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 adult-onset (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.

 

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]], [[Prader–Willi 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.

 

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]].

 

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.<ref name="pmid12147369">{{cite journal | author = Swerdlow AJ, Higgins CD, Adlard P, Preece MA | title = Risk of cancer in patients treated with human pituitary growth hormone in the UK, 1959-85: a cohort study | journal = Lancet | volume = 360 | issue = 9329 | pages = 273–7 | year = 2002 | month = July | pmid = 12147369 | doi = 10.1016/S0140-6736(02)09519-3 | url = | issn = }}</ref>

 

{{Main|HGH treatment for athletic enhancement}}

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.<ref>http://www.bloomberg.com/apps/news?pid=20601124&sid=awlswGxIiU5c&refer=home</ref><ref>http://grg51.typepad.com/steroid_nation/2008/03/review-from-sta.html</ref> 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 doctor.

 

 

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]].

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.<ref>http://www.fda.gov/downloads/AnimalVeterinary/DevelopmentApprovalProcess/UCM071853.pdf</ref><ref>http://www.lemars.k12.ia.us/ag/AgriScience%202%20class/Animal%20Nutrition%20Unit/Growth%20promoters%20in%20AS.pdf</ref>

 

{{Main|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 DNA|recombinant]] human growth hormone for human therapy in 1981.

As of 2005, recombinant growth hormones available in the United States (and their manufacturers) included Nutropin ([[Genentech]]), Humatrope ([[Eli Lilly and Company|Lilly]]), Genotropin ([[Pfizer]]), Norditropin ([[Novo Nordisk|Novo]]), and Saizen ([[Merck Serono]]). In 2006, the U.S. Food and Drug Administration (FDA) approved a version of [[rHGH]] called [[Omnitrope]] (Sandoz). A sustained-release 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<ref>Genentech and Alkermes Announce Decision to Discontinue Commercialization of Nutropin Depot. http://findarticles.com/p/articles/mi_m0EIN/is_2004_June_1/ai_n6050768/</ref>).

 

 

As described above, the idea that GH can be used to combat aging has entered American culture, and many companies selling [[dietary supplements]] have websites selling products that are linked to GH in the advertising text, and have medical-sounding names, but upon closer examination are described as "HGH Releasers" or the like, and when one examines the list of ingredients, the products are described as being made of amino acids, minerals, vitamins, and/or herbal extracts, the combination of which are described as causing the body to make more GH and by that means, having several beneficial effects. Examples<ref>[http://www.secratatropinhgh.com Secratropin]</ref><ref>[http://www.advice-hgh.com/igf-1.html#sytropin Syntropin]</ref> are easy to find via a web search. 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, since these products are dietary supplements, under United States law, the companies that sell them in the United States cannot make 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; examples<ref>[http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm215918.htm Warning Letter - Atlas Operations, Inc]</ref> can be found on the FDA website.