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Growth hormone
growth hormone 1
Identifiers
Symbol GH1
Entrez 2688
HUGO 4261
OMIM 139250
RefSeq NM_022562
UniProt P01241
Other data
Locus Chr. 17 q22-q24
"HGH" redirects here. The Entrez Global Query Cross-Database Search System is a powerful Federated search engine or Web portal that allows users to search many discrete Health sciences The Human Genome Organisation (HUGO is an organization involved in the Human Genome Project, a project about mapping the human genome The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The National Center for Biotechnology Information ( NCBI) is part of the United States National Library of Medicine (NLM a branch of the National Institutes Swiss-Prot is a manually curated Biological database of Protein sequences In the fields of Genetics and Evolutionary computation, a locus (plural loci) is a fixed position on a Chromosome such as the position of a Chromosome 17 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome For other uses, see HGH (disambiguation).

Growth hormone (GH) is a hormone that stimulates growth and cell reproduction in humans and other animals. Hormones (from Greek ὁρμή - "impetus" are chemicals released by cells that affect cells in other parts of the body Human development is the process of Growing to maturity In biological terms this entails growth from a one-celled Zygote to an adult Human being The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called 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. Peptides (from the Greek πεπτίδια, "small digestibles" are short Polymers formed from the linking in a defined order of α- Amino Somatotropes are cells in the Anterior pituitary which produce Growth hormone. The anterior pituitary (also called the adenohypophysis, from Greek adeno, "gland" hypo, "under" physis, "growth" Somatotrophin refers to the growth hormone produced natively in animals, the term somatropin refers to growth hormone produced by recombinant DNA technology[1], and is abbreviated "rhGH". Recombinant DNA is a form of synthetic DNA that is engineered through the combination or insertion of one or more DNA strands thereby combining DNA sequences 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.

Contents

Gene locus

Main article: 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 human chorionic somatomammotropin (also known as placental lactogen) genes. Growth hormone 1, also known as GH1, is a human Gene. Growth hormone 1, also known as GH1, is a human Gene. Placental lactogen is a Polypeptide Placental Hormone. Its structure and function is similar to that of Growth hormone. GH, human chorionic somatomammotropin, and prolactin (PRL) are a group of homologous hormones with growth-promoting and lactogenic activity. Prolactin ( PRL) or Luteotropic hormone ( LTH) is a Peptide hormone primarily associated with Lactation. In Evolutionary biology, homology has come to mean any similarity between characters that is due to their shared ancestry.

Molecular structures

The major isoform of the human growth hormone is a protein of 191 amino acids and a molecular weight of 22 124 daltons. In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this The unified atomic mass unit ( u) or Dalton ( Da) or sometimes universal mass unit, is an unit of Mass used to express 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. In Biology, a species is one of the basic units of Biological classification and a Taxonomic rank. A primate is a member of the biological order Primates ( Latin: "prime first rank" the group that contains Lemurs the Aye-aye

Secretion

Several molecular isoforms of GH circulate in the plasma. In Chemistry, a molecule is defined as a sufficiently stable electrically neutral group of at least two Atoms in a definite arrangement held together by 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). Growth hormone binding protein is as its name would indicate a Carrier protein for Growth hormone. Growth hormone receptor, also known as GHR, is a human Gene.

Regulation

Peptides released by neurosecretory nuclei of the hypothalamus (Growth hormone releasing hormone and somatostatin) into the portal venous blood surrounding the pituitary are the major controllers of GH secretion by the somatotropes. The hypothalamus links the Nervous system to the Endocrine system via the Pituitary gland (hypophysis In the Circulatory system of animals a portal venous system occurs when a Capillary bed drains into another capillary bed through Veins Both capillary 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). [2]

Stimulators of GH secretion include:

Inhibitors of GH secretion include:

In addition to control by endogenous processes, a number of foreign compounds (xenobiotics) are now known to influence GH secretion and function [4], highlighting the fact that the GH-IGF axis is an emerging target for certain endocrine disrupting chemicals (see endocrine disruptor). Growth-hormone-releasing hormone (GHRH also known as growth-hormone-releasing factor (GRF or GHRF or somatocrinin, is a 44- Amino acid Peptide hormone The arcuate nucleus (or infundibular nucleus is an aggregation of Neurons in the mediobasal Hypothalamus, adjacent to the Third ventricle and the Median Ghrelin is a Hormone produced mainly by P/D1 cells lining the fundus of the human Stomach and epsilon cells of the Pancreas that stimulates Blood sugar, used in a physiological context is a misnomer and misleading Hypoglycemia or hypoglycaemia is the medical term for a pathologic state produced by a lower than normal level of Glucose ( sugar) in the blood Estradiol (17β-estradiol (also oestradiol) is a Sex hormone. Arginine (abbreviated as Arg or R) is an α- Amino acid. The L-form is one of the 20 most common natural amino acids Somatostatin (also known as growth hormone inhibiting hormone ( GHIH) or somatotropin release-inhibiting factor ( SRIF) is a Peptide hormone The Periventricular nucleus is a composite structure of the Hypothalamus. Insulin-like growth factor 1 (IGF-1 that was once called somatomedin C is a Polypeptide Protein Hormone similar in Molecular structure Negative Feedback feeds part of a System 's output inverted into the system's input generally with the result that fluctuations are attenuated Hyperglycemia, hyperglycaemia, or high blood sugar is a condition in which an excessive amount of Glucose circulates in the Blood plasma Glucocorticoids (GC are a class of Steroid hormones characterised by an ability to bind with the glucocorticoid receptor ( GR) and trigger similar effects A xenobiotic is a Chemical which is found in an Organism but which is not normally produced or expected to be present in it Endocrine disruptors (sometimes also referred to as hormonally active agents) are Exogenous substances that act like Hormones in the Endocrine system

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. [5] 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 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 anabolic (building up) as well as people with short stature, grow taller. Anabolism is the set of Metabolic pathways that construct molecules from smaller units Like most other protein hormones GH acts by interacting with a specific receptor on the surface of cells. In Biochemistry, a receptor is a Protein molecule embedded in either the Plasma membrane or Cytoplasm of a cell to which a mobile signaling

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.

  1. GH directly stimulates division and multiplication of chondrocytes of cartilage. Chondrocytes (from Greek chondros cartilage + kytos cell are the only cells found in Cartilage. Cartilage is a type of dense Connective tissue. It is composed of specialized cells called chondrocytes that produce a large amount of extracellular matrix These are the primary cells in the growing ends (epiphyses) of children's long bones (arms, legs, digits). Epiphysis is the name for a rounded end of a long Bone. The epiphysis is filled with red Bone marrow, which produces Erythrocytes, or red blood cells
  2. GH also stimulates production of insulin-like growth factor 1 (IGF-1, formerly known as somatomedin C), a hormone homologous to proinsulin. Insulin-like growth factor 1 (IGF-1 that was once called somatomedin C is a Polypeptide Protein Hormone similar in Molecular structure Proinsulin is the Prohormone precursor to Insulin made in the Beta cell of the Islets of Langerhans. [6] The liver is a major target organ of GH for this process, and is the principal site of IGF-1 production. The liver is a vital organ in the human body and is present in Vertebrates and some other animals 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 and an autocrine/paracrine hormone. Endocrine glands are Glands that secrete their product ( Hormones, directly into the blood rather than through a duct Autocrine signaling is a form of signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent that binds to autocrine receptors on the same cell leading Paracrine signaling is a form of Cell signaling in which the target cell is near (" Para " = near the signal-releasing cell 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:

Excesses

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. An adenoma is a collection of growths (-oma of glandular origin 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. Acromegaly (from Greek akros "extreme" or "extremities" and megalos "large" - extremities enlargement is a Syndrome Accompanying problems can include pressure on nerves (e. g. , carpal tunnel syndrome), muscle weakness, insulin resistance or even a rare form of type 2 diabetes, and reduced sexual function. Carpal tunnel syndrome (CTS or median neuropathy at the wrist is a medical condition in which the Median nerve is compressed at the Wrist, leading Diabetes mellitus type 2 or Type 2 Diabetes (formerly called non - Insulin -dependent Diabetes mellitus (NIDDM or adult-onset diabetes is a metabolic

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. Gigantism or giantism, (from Greek gigas, gigantas " giant " is a condition characterized by excessive growth and height

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 article: Growth hormone deficiency

The effects of growth hormone deficiency vary depending on the age at which they occur. Growth Hormone Deficiency is the medical condition of inadequate production of Growth hormone (GH and it effects on children and adults Growth Hormone Deficiency is the medical condition of inadequate production of Growth hormone (GH and it effects on children and adults In children, growth failure and short stature are the major manifestations of GH deficiency. It can also cause sexual immaturity. 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. Recombinant DNA is a form of synthetic DNA that is engineered through the combination or insertion of one or more DNA strands thereby combining DNA sequences As GH is a large protein molecule, it must be injected subcutaneously to access the bloodstream (injections no longer have to enter muscle mass since 1985 with the production of synthetic GH). An injection is an infusion method of putting Liquid into the Body, usually with a hollow needle and a Syringe which is pierced through 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. Turner syndrome or Ullrich-Turner syndrome encompasses several conditions of which monosomy X is the most common Chronic kidney disease (CKD also known as chronic renal disease, is a progressive loss of renal function over a period of months or years Prader-Willi syndrome (abbreviated PWS) is a very rare Genetic disorder, in which seven genes (or some subset thereof on chromosome 15 are missing or unexpressed Birth weight is the weight of a baby at its birth. It has direct links with the Gestational age at which the child was born and can be estimated Idiopathic short stature (ISS refers to extreme Short stature that does not have a diagnostic explanation ( idiopathic designates a condition 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. Wasting could also mean unefficient and/or uneffective consumption. GH can also be used in patients with short bowel syndrome to lessen the requirement for intravenous total parenteral nutrition. Short bowel syndrome ( SBS, also short gut syndrome or simply short gut) is a Malabsorption disorder caused by the surgical removal Total Parenteral nutrition (TPN is the practice of feeding a person Intravenously bypassing the usual process of Eating and Digestion.

Uses that are controversial include

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. Multiple sclerosis (abbreviated MS also known as disseminated sclerosis or encephalomyelitis disseminata) is an autoimmune condition in which the Ageing or aging (American English is the accumulation of changes in an organism Weight loss, in the context of Medicine or Health or Physical fitness, is a reduction of the total Body weight, due to a mean loss of fluid Obesity is a condition in which excess Body fat has accumulated to such an extent that health may be negatively affected Fibromyalgia (FM is a disorder classified by the presence of chronic widespread Pain and tactile Allodynia. Crohn's disease is a Disease of the Digestive system which may affect any part of the Gastrointestinal tract from Mouth to Anus Ulcerative colitis ( Colitis ulcerosa, UC) is a form of Inflammatory bowel disease (IBD Growth hormone (GH is a protein Hormone secreted by the Pituitary gland which stimulates growth and cell reproduction Bovine somatotropin (abbreviated bST and BST) is a protein hormone produced in the Pituitary glands of Cattle. Dairy farming is a class of agricultural, or an Animal husbandry enterprise for long-term production of Milk, which may be either processed on-site or Cattle, colloquially referred to as cows, are domesticated Ungulates a member of the Subfamily Bovinae of the family 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 were the kind of changes that would occur naturally 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 mis-interpreted as indicating GH was an effective anti-aging agent. [8]

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. [8] 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. [8] 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. Carpal tunnel syndrome (CTS or median neuropathy at the wrist is a medical condition in which the Median nerve is compressed at the Wrist, leading Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc [8]

Side effects

Main article: 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. There are many controversies around the claims products and businesses related to the use of Growth hormone as an anti-aging therapy. 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. [9]

History

Main article: Growth hormone treatment#History

The identification, purification and later synthesis of growth hormone is associated with Choh Hao Li. Growth hormone (GH is a protein Hormone secreted by the Pituitary gland which stimulates growth and cell reproduction Choh Hao Li (sometimes Cho Hao Li) ( Chinese: 李卓皓 Pinyin: Lǐ Zhuōhào ( April 21, 1913 &mdash November 28, Genentech pioneered the first use of recombinant human growth hormone for human therapy in 1981. Genentech Inc ( a composite of Genetic Engineering Technology Inc Recombinant DNA is a form of synthetic DNA that is engineered through the combination or insertion of one or more DNA strands thereby combining DNA sequences

Prior to its production by recombinant DNA technology, growth hormone used to treat deficiencies was extracted from the pituitary glands of cadavers. The pituitary gland, or hypophysis, is an Endocrine gland about the size of a Pea. A cadaver or corpse is a dead Body. "Cadaver" is normally used as a more formal term for a body being used in medical training or research 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 (Lilly), Genotropin (Pfizer), Norditropin (Novo), and Saizen (Merck Serono). Genentech Inc ( a composite of Genetic Engineering Technology Inc Eli Lilly and Company ( is a global Pharmaceutical company and one of the world's largest corporations Pfizer Incorporated ( is a major Pharmaceutical company, which ranks number one in the world in sales Novo Nordisk () manufactures and markets Pharmaceutical products and services Collaborative Research In addition to internal research and development activities Merck Serono is also involved in publicly funded collaborative research projects with other industrial 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

  1. ^ e. g. , Daniels, M. E. (1992). "Lilly's Humatrope Experience". Nature Biotechnology 10: 812.  
  2. ^ Actions of Anterior Pituitary Hormones: Growth Hormone (GH). Medical College of Georgia. 2007.
  3. ^ Alba-Roth J, Müller O, Schopohl J, von Werder K (1988). "Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion". J Clin Endocrinol Metab 67 (6): 1186-9. PMID 2903866.  
  4. ^ Scarth J. "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". Xenobiotica 36 (2-3): 119-218. PMID 16702112.  
  5. ^ Takahashi Y, Kipnis D, Daughaday W (1968). "Growth hormone secretion during sleep". J Clin Invest 47 (9): 2079-90. PMID 5675428.  
  6. ^ Actions of Anterior Pituitary Hormones: Physiologic Actions of GH. Medical College of Georgia (2007). Retrieved on 2008-01-16. 2008 ( MMVIII) is the current year in accordance with the Gregorian calendar, a Leap year that started on Tuesday of the Common Events 27 BC - The title Augustus is bestowed upon Gaius Julius Caesar Octavian by the Roman Senate.
  7. ^ King, MW (2006). Structure and Function of Hormones: Growth Hormone. Indiana State University. Indiana State University ( ISU) is a Public university that is located in Terre Haute Indiana, United States. Retrieved on 2008-01-16. 2008 ( MMVIII) is the current year in accordance with the Gregorian calendar, a Leap year that started on Tuesday of the Common Events 27 BC - The title Augustus is bestowed upon Gaius Julius Caesar Octavian by the Roman Senate.
  8. ^ a b c d Liu H, Bravata DM, Olkin I, et al (2007). "Systematic review: the safety and efficacy of growth hormone in the healthy elderly". Ann. Intern. Med. 146 (2): 104–15. PMID 17227934.  ; news report
  9. ^ Swerdlow AJ, Higgins CD, Adlard P, Preece MA (2002). "Risk of cancer in patients treated with human pituitary growth hormone in the UK, 1959-85: a cohort study". Lancet 360 (9329): 273–7. doi:10.1016/S0140-6736(02)09519-3. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12147369.  

Dictionary

growth hormone

-noun

  1. Any polypeptide hormone, secreted by the pituitary gland, that promotes growth and regulates the metabolism of carbohydrates, proteins and lipids.
  2. Any synthetic substance that promotes growth in animals or plants.
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