Growth hormone 173072 226036121 2008-07-16T15:22:32Z 129.59.82.154 rv vandalism {{Refimprove|date=January 2008}} {{protein | Name = growth hormone 1 | caption = Growth hormone | image = Somatotropine.GIF | width = 240 | HGNCid = 4261 | Symbol = GH1 | AltSymbols = | EntrezGene = 2688 | OMIM = 139250 | RefSeq = NM_022562 | UniProt = P01241 | PDB = | ECnumber = | Chromosome = 17 | Arm = q | Band = 22 | LocusSupplementaryData = -q24 }} {{Redirect|HGH}} '''Growth hormone''' ('''GH''') is a [[hormone]] that stimulates [[human development (biology)|growth]] and [[cell (biology)|cell]] reproduction in humans and other animals. It is a 191-amino acid, single chain [[polypeptide]] hormone which is synthesized, stored, and secreted by the [[somatotroph]] cells within the lateral wings of the [[anterior pituitary]] gland. '''Somatotrophin''' refers to the growth hormone produced natively in animals, the term somatropin refers to growth hormone produced by [[recombinant DNA technology]]<ref>e.g., {{cite journal |author=Daniels, M.E. |title=Lilly's Humatrope Experience |journal=Nature Biotechnology |volume=10 |pages=812 |year=1992}}</ref>, and is abbreviated "rhGH" in human. Growth hormone has a variety of functions in the body, the most noticeable of which is the increase of height throughout childhood, and there are several diseases which can be treated through the therapeutic use of GH. ==Gene locus== {{main|Growth hormone 1}} The genes for human growth hormone, known as [[Growth hormone 1]], are localized in the q22-24 region of chromosome 17 and are closely related to [[somatomammotropin|human chorionic somatomammotropin]] (also known as [[placental lactogen]]) genes. GH, human chorionic somatomammotropin, and [[prolactin]] (PRL) are a group of [[homology (biology)|homologous]] hormones with growth-promoting and lactogenic activity. ==Molecular structures== The major isoform of the human growth hormone is a protein of 191 [[amino acid]]s and a molecular weight of 22 124 [[Atomic mass unit|daltons]]. The structure includes four helices necessary for functional interaction with the GH receptor. GH is structurally and apparently 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. ==Secretion== Several [[molecule|molecular]] isoforms of GH circulate in the plasma. Much of the growth hormone in the circulation is bound to a protein ([[growth hormone binding protein]], GHBP) which is derived from the [[growth hormone receptor]], and an acid label sub unit (ALS). ===Regulation=== Peptides released by neurosecretory nuclei of the [[hypothalamus]] (Growth hormone releasing hormone and somatostatin) into the [[portal system|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>[http://www.lib.mcg.edu/edu/eshuphysio/program/section5/5ch2/s5ch2_18.htm Actions of Anterior Pituitary Hormones: Growth Hormone (GH)]. Medical College of Georgia. 2007.</ref> ''Stimulators'' of GH secretion include: * [[growth hormone releasing hormone]] (GHRH) from the [[arcuate nucleus]] * [[ghrelin]] * sleep * exercise * low levels of [[blood sugar]] ([[hypoglycemia]]) * dietary protein * increased androgen secretion during puberty (in males from testis and in females from adrenal cortex) * [[arginine]]<ref>{{cite journal |author=Alba-Roth J, Müller O, Schopohl J, von Werder K |title=Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion |journal=J Clin Endocrinol Metab |volume=67 |issue=6 |pages=1186–9 |year=1988 |pmid=2903866 |doi=10.1126/science.2237411.<br> |doi_brokendate=2008-06-26}}</ref> ''Inhibitors'' of GH secretion include: * [[somatostatin]] from the [[periventricular nucleus]] * circulating concentrations of GH and [[IGF-1]] ([[negative feedback]]) * [[hyperglycemia]] * [[glucocorticoid]]s * [[estradiol]] In addition to control by endogenous processes, a number of foreign compounds ([[xenobiotics]]) are now known to influence GH secretion and function <ref>{{cite journal |author=Scarth J |title=Modulation of the growth hormone-insulin-like growth factor (GH-IGF) axis by pharmaceutical, nutraceutical and environmental xenobiotics: an emerging role for xenobiotic-metabolizing enzymes and the transcription factors regulating their expression. A review |journal=Xenobiotica |volume=36 |issue=2-3 |pages=119–218 |year= |pmid=16702112}}</ref>, highlighting the fact that the GH-IGF axis is an emerging target for certain endocrine disrupting chemicals (see [[endocrine disruptor]]). ===Secretion patterns=== Most of the physiologically important secretion occurs as several large pulses or peaks of GH release each day. The plasma concentration of GH during these peaks may range from 5 to 35 ng/mL or more. Peaks typically last from 10 to 30 minutes before returning to basal levels. The largest and most predictable of these GH peaks occurs about an hour after onset of sleep.<ref>{{cite journal |author=Takahashi Y, Kipnis D, Daughaday W |title=Growth hormone secretion during sleep |journal=J Clin Invest |volume=47 |issue=9 |pages=2079–90 |year=1968 |pmid=5675428 |doi=10.1172/JCI105893}}</ref> Otherwise there is wide variation between days and individuals. Between the peaks, basal GH levels are low, usually less than 3 ng/mL for most of the day and night. The amount and pattern of GH secretion change throughout life. Basal levels are highest in early childhood. The amplitude and frequency of peaks is greatest during the [[puberty|pubertal]] growth spurt. Healthy children and adolescents average about 8 peaks per 24 hours. Adults average about 5 peaks. Basal levels and the frequency and amplitude of peaks decline throughout adult life. Also may have impact/help growth of colon, lung, and breast cancer. ==Functions of GH== Effects of growth hormone on the tissues of the body can generally be described as [[anabolism|anabolic]] (building up) as well as people with short stature, grow taller. Like most other protein hormones GH acts by interacting with a specific [[receptor (biochemistry)|receptor]] on the surface of cells. Stimulating the increase in height in childhood is the most widely known effect of GH, and appears to be stimulated by at least two mechanisms. # GH directly stimulates division and multiplication of [[chondrocytes]] of [[cartilage]]. These are the primary cells in the growing ends ([[epiphysis|epiphyses]]) of children's long bones (arms, legs, digits). # GH also stimulates production of [[insulin-like growth factor 1]] (IGF-1, formerly known as somatomedin C), a hormone homologous to [[proinsulin]].<ref>{{cite web | url = http://www.lib.mcg.edu/edu/eshuphysio/program/section5/5ch2/s5ch2_19.htm | title = Actions of Anterior Pituitary Hormones: Physiologic Actions of GH | publisher = Medical College of Georgia | date = 2007 | accessdate = 2008-01-16 }}</ref> 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 apparently both an [[endocrine gland|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 the [[sarcomere]] [[hyperplasia]] * Promotes [[lipolysis]] * Increases [[protein synthesis]] * Stimulating the growth of all internal organs excluding the [[brain]] * Plays a role in fuel [[homeostasis]]. * Reduces [[liver]] uptake of [[glucose]] * Promotes [[gluconeogenesis]] in the liver<ref>{{cite web | first = MW | last = King | url = http://web.indstate.edu/thcme/mwking/peptide-hormones.html#gh | title = Structure and Function of Hormones: Growth Hormone | publisher = [[Indiana State University]] | date = 2006 | accessdate = 2008-01-16 }}</ref> * It contributes to the maintenance and function of [[pancreatic islets]]. * It stimulates the [[immune system]]. ===Excesses=== The most common disease of GH excess is a pituitary tumor composed of somatotroph cells of the anterior pituitary. These somatotroph [[adenoma]]s 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 thickness of digits is referred to as [[acromegaly]]. Accompanying problems can include pressure on nerves (e.g., [[carpal tunnel syndrome]]), muscle weakness, insulin resistance or even a rare form of [[Diabetes mellitus type 2|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 [[gigantism|pituitary gigantism]]. Surgical removal is the usual treatment for GH-producing tumors. In some circumstances focused radiation or a GH antagonist such as bromocriptine or octreotide may be employed to shrink the tumor or block function. ===Deficiencies=== {{main|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. It can also cause delayed sexual maturity. In adults the effects of deficiency are more subtle, and may include deficiencies of strength, energy, and bone mass, as well as increased cardiovascular risk. There are many causes of GH deficiency, including mutations of specific genes, congenital malformations involving the hypothalamus and/or pituitary gland, and damage to the pituitary from injury, surgery or disease. Diagnosis of GH deficiency involves a multiple step diagnostic process, usually culminating in GH stimulation test(s) to see if the patient's pituitary gland will release a pulse of GH when provoked by various stimuli. Deficiency is treated through supplementation with external GH. All GH in current use is a biosynthetic version of human GH, manufactured by [[recombinant DNA]] technology. As GH is a large protein molecule, it must be [[Injection (medicine)#Subcutaneous injection|injected subcutaneously]] to access the bloodstream (injections no longer have to enter muscle mass since 1985 with the production of synthetic GH)<!-- HUH? WHAT IS THIS SECTION TRYING TO SAY? LAY READERS WOULD NOT QUESTION THE ABSENCE OF INTRAMUSCULAR INJECTION AS IT'S NOT MENTIONED PREVIOUSLY IN THE ARTICLE -->. When the patient has had a long-standing deficiency of GH benefits of treatment are often dramatic and side effects of treatment are rare. Increased growth in childhood can result in dramatically improved adult height. 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. ==Therapeutic use== ===Treatments unrelated to deficiency=== GH can be used to treat conditions which produce short stature but are not related to deficiencies in GH, though results are not as dramatic when compared to short stature solely due 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 physiologic. Despite the higher doses, side effects during treatment are rare, and vary little according to the condition being treated. GH treatment improves muscle strength and slightly reduces body fat in Prader-Willi syndrome, which are significant concerns beyond the need to increase height. GH is also useful in maintaining muscle mass in [[wasting]] due to [[AIDS]]. GH can also be used in patients with [[short bowel syndrome]] to lessen the requirement for intravenous [[total parenteral nutrition]]. Uses that are controversial include * GH treatment for remission of [[Multiple sclerosis]] * GH treatment to reverse effects of [[aging]] in older adults (see [[#Anti-aging agent|below]]) * GH treatment to enhance [[weight loss]] in [[obesity]] * GH treatment for [[fibromyalgia]] * GH treatment for [[sytropin]] * GH treatment for [[Crohn's disease]] and [[ulcerative colitis]] * GH treatment for idiopathic short stature * GH treatment for [[growth hormone treatment for bodybuilding|bodybuilding]] or athletic enhancement * The use of [[bovine somatotropin]] to increase [[milk production]] in [[cattle]] ===Anti-aging agent === Claims for GH as an anti-aging treatment date back to 1990 when the ''New England Journal of Medicine'' published a study where GH was used to treat 12 men over 60. 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 GH was an effective anti-aging agent. <ref name="physorg">{{cite journal |author=Liu H, Bravata DM, Olkin I, ''et al'' |title=Systematic review: the safety and efficacy of growth hormone in the healthy elderly |journal=Ann. Intern. Med. |volume=146 |issue=2 |pages=104–15 |year=2007 |pmid=17227934 |doi=}}; [http://www.physorg.com/news88140162.html news report]</ref> 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.<ref name="physorg"/> 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.<ref name="physorg"/> Researchers also didn't discover any gain in muscle strength, which led them to believe that GH merely let the body to store more water in the muscles rather than increase muscle growth. This would explain the increase in lean body mass. Regular application of GH did show several negative side effects such as joint swelling, joint pain, [[carpal tunnel syndrome]], and an increased risk of [[diabetes]].<ref name="physorg"/> ===Side effects=== {{main|HGH controversies}} There is theoretical concern that GH treatment may increase the risks of diabetes, especially in those with other predispositions treated with higher doses. One survey of adults who 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, but linkage with the GH treatment was not established.<ref>{{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 |pmid=12147369|doi=10.1016/S0140-6736(02)09519-3}}</ref> ==History == {{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. Prior to its production by recombinant DNA technology, growth hormone used to treat deficiencies was extracted from the [[pituitary gland]]s of [[cadaver]]s. In 1985, biosynthetic human growth hormone replaced pituitary-derived human growth hormone for therapeutic use in the U.S. and elsewhere. GH is also known to increase chances of breast cancer and lung cancer. 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 Association (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 in 2004. ==References== {{reflist}} [[ar:هرمون النمو]] [[bg:Соматотропин]] [[cs:Růstový hormon]] [[de:Somatotropin]] [[dv:ގްރޯޘް ހޯރމޯން]] [[es:Hormona somatotropa]] [[fr:Hormone de croissance]] [[id:Hormon pertumbuhan]] [[it:Somatotropina]] [[he:הורמון גדילה]] [[lt:Somatotropinas]] [[mk:Соматотропин]] [[nl:Groeihormoon]] [[no:Veksthormon]] [[ja:成長ホルモン]] [[pl:Hormon wzrostu]] [[pt:Hormônio do crescimento]] [[ru:Соматотропный гормон]] [[sq:Somatropina]] [[sl:Rastni hormon]] [[sr:Хормон раста]] [[fi:Somatotropiini]] [[sv:Tillväxthormon]] [[sk:Somatotropín]]