Human growth hormone: Difference between revisions
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<StructureSection load=' | <StructureSection load='3hhr' size='350' side='right' caption='Human growth hormone and the extracellular domain of its receptor (PDB entry [[3hhr]])' scene=''> | ||
==Function== | ==Function== | ||
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Mature hGH travels through the bloodstream and interacts with a specific hGH-receptor on the surface of various cells, including muscle, bone, and cartilage. Binding of hGH to its receptor causes dimerization and signal transduction, which ultimately stimulates cellular division. HGH also indirectly influences growth by stimulating the liver to produce additional growth factors, such as insulin-like growth factor-1. Synthetic versions of hGH produced by recombinant DNA technology are used to treat growth disorders associated with hGH deficiencies. [[Prolactin receptor]] (PRLR) can also bind to and be activated by growth hormone. | Mature hGH travels through the bloodstream and interacts with a specific hGH-receptor on the surface of various cells, including muscle, bone, and cartilage. Binding of hGH to its receptor causes dimerization and signal transduction, which ultimately stimulates cellular division. HGH also indirectly influences growth by stimulating the liver to produce additional growth factors, such as insulin-like growth factor-1. Synthetic versions of hGH produced by recombinant DNA technology are used to treat growth disorders associated with hGH deficiencies. [[Prolactin receptor]] (PRLR) can also bind to and be activated by growth hormone. | ||
See also [[HUMAN GROWTH HORMONE (HEBREW)]] | |||
==Location in the Body== | ==Location in the Body== | ||
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Glycosylation helps distinguish between different variants and isoforms as it works as an ID cards for proteins. These carbohydrates are specific to each forms and are recognized by the associated hgH receptors. Though still being a relatively unknown mechanism in hgH, studies have shown that one isoform in particular, a 22kDa variant was identified and discovered due to the specific carbohydrates linked to its polypeptide chain (M.Kirstein 1992). | Glycosylation helps distinguish between different variants and isoforms as it works as an ID cards for proteins. These carbohydrates are specific to each forms and are recognized by the associated hgH receptors. Though still being a relatively unknown mechanism in hgH, studies have shown that one isoform in particular, a 22kDa variant was identified and discovered due to the specific carbohydrates linked to its polypeptide chain (M.Kirstein 1992). | ||
==Secretion Mechanism== | |||
It was previously believed that after stimulating HGH secretion, membrane bound secretory vesicles containing the hormone dock at the cell plasma membrane. These vesicles were believed to become completely incorporated into the plasma membrane, and would later be retrieved via endocytosis, thus allowing for passive release of the HGH within the vesicles. However, this mechanism is not supported by experimental evidence, such as the appearance of empty and partially empty vesicles immediately after secretion. Bhanu Jena’s laboratory has recently elucidated the molecular mechanism of cellular secretion. Their studies suggest that there is actually a new cellular structure called a porosome that is involved with the mechanism. Porosomes are “basket-like” structures residing at the plasma membrane that have a 100-150nm diameter opening to the extracellular environment (Figure 1). It involves several specific proteins like SNAP receptors or N-ethylmaleimide-sensitive factor. First, the GH is brought to the porosome using ATP and kinesins along microtubules. Then, rather than docking directly at the plasma membrane post secretion stimulation, membrane bound secretory vesicles fuse at the base of porosomes, which subsequently expel the vesicular contents (Figure 2). During stimulation, the opening dilates about 20-35% to aid in the expulsion of HGH. The porosome returns to the resting size once the process is complete (Anderson et al., 2004)<ref>PMID:15305891</ref>. | |||
Several hypothalamic hormones that control growth hormone release exist. The most major of these secretion stimuli is the growth hormone release factor (GHRH). Another factor has been discover : ghrelin is an acylated peptide directly responsible for a GH secretion from somatotropes. In contrast, the hormone known as somatostatin (SRIF) is known to suppress the release of GH by the somatotrope. These two hormones are the most well known, though it should be noted that there are multiple other control factors which both stimulate and suppress the release of HGH into the bloodstream (Anderson et al., 2004). | |||
== | ==Mechanism of Action== | ||
In order to facilitate this behavior as a hormone somatotropin binds to two receptors on the outside of a cell known as Human Growth Hormone Binding Proteins (hGHpb). Once the Human Growth hormone binds both receptors (first one, then the second), it causes a shift in the receptor protein, which in turn causes an internal signaling cascade. This cascade is how somatotropin is able to effect cell growth and function. In addition it can cause the release of other growth factors, like Insulin Growth Factor. | |||
Examples : | |||
For Growth : | |||
HGH is especially important for the growth of cartilage and bone. It’s efficiency will increase even more during the adolescent years when it is more produced. | |||
Insulin-like growth factor-1 binds to its receptor, IGF-1R, on the cellular surface and activates a tyrosine kinase-mediated intracellular signaling pathway that phosphorylates various proteins intracellularly leading to increased metabolism, anabolism, and cellular replication and division. Furthermore, it acts to inhibit apoptosis of the cell, thus prolonging the lifespan of existing cells. The net result is to encourage the growth of tissue and to create a hyperglycemic environment in the body. | |||
==Inhibitors== | ==Inhibitors== | ||
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Diseases associated with human growth hormone are related to deficiency or overproduction of the hormone. | Diseases associated with human growth hormone are related to deficiency or overproduction of the hormone. | ||
Deficiency in somatostatin can occur in childhood or adulthood. Congenital deficiency is typically associated with an abnormal pituitary gland but can also be part of a larger syndrome or condition1. Acquired deficiency can develop from multiple sources including infection, brain tumors, injury, brain surgery or radiation to the head1.Pituitary tumors which have been treated with surgery or radiation are the typically cause of GH deficiency in adults. | |||
Symptoms of deficiency in children include short stature, slow growth, late onset of puberty, increased fat around the waist, and delayed tooth development1. Pituitary dwarfism can result from untreated deficiency in children. In adults the symptoms include decreased strength and muscle mass, weight gain, anxiety and can increased total cholesterol and triglyceride levels. | |||
The Turner syndrome is classified as a type of dwarfism affecting girls. It is a chromosomal disorder due to a partial or complete absence of an X chromosome. | |||
The general treatment for dwarfism is HgH injections. The sooner this treatment is started, the more effective it will be. These injections are applied anywhere from several times a week to once a day. | |||
Injection of GH has been implicated in the development of Creutzfeldt-Jakob Disease. Several cases of such disease were proven related to subjects being recipient of pituitary derived hGH. This association has only been found in GH isolated from cadavers. Originally isolation of the protein from cadavers was the method of development for replacement therapies. Now recombinant methods of production are the main method for synthesis. There seems to be no association in recombinant DNA-produced GH and Creutzfeldt-Jakob disease2. | |||
Diseases can also result from levels of GH being too high. The effects of excess GH vary based on age. Gigantism is excess of GH during childhood and Acromegaly is excess of GH during adulthood (after bone growth has stopped). Symptoms of gigantism include delayed puberty, headache, increased sweating, and weakness3. Symptoms of acromegaly vary slightly and include carpal tunnel syndrome, weakness, joint pain, sleep apnea, and unintentional weight loss4. | |||
Diseases can also result from levels of GH being too high. The effects of excess GH vary based on age. Gigantism is excess of GH during childhood and Acromegaly is excess of GH during adulthood (after bone growth has stopped). Symptoms of gigantism include delayed puberty | |||
Excess GH release most often occurs because of a pituitary gland tumor3. It can also be due to Carney complex, McCune-Albright syndrome, multiple endocrine neoplasia type 1, and neurofibromatosis3. Treatment includes medications to decrease hormone release and, in severe cases, removal of the pituitary gland. | Excess GH release most often occurs because of a pituitary gland tumor3. It can also be due to Carney complex, McCune-Albright syndrome, multiple endocrine neoplasia type 1, and neurofibromatosis3. Treatment includes medications to decrease hormone release and, in severe cases, removal of the pituitary gland. | ||
Acromegaly | Acromegaly is most commonly treated with surgery. Removing the tumor in the pituitary gland can stop the excess release of growth hormone. Incomplete success of the surgery is often attributed to the size of the tumor: large tumors cannot always be completely removed, resulting in continued high levels of hormone release (Freda, 2002)<ref>PMID:9814451</ref>. | ||
Surgery is often supplemented, or in some cases replaced, by radiation therapy. Radiation of the pituitary can help reduce levels of hormone release by killing tumor cells, but reduction of release as a result of radiation is a slow process and is not as successful as surgery. For this reason, it is more commonly used in tandem with surgery, rather than alone (Freda, 2002; A.D.A.M. Acromegaly). | Surgery is often supplemented, or in some cases replaced, by radiation therapy. Radiation of the pituitary can help reduce levels of hormone release by killing tumor cells, but reduction of release as a result of radiation is a slow process and is not as successful as surgery. For this reason, it is more commonly used in tandem with surgery, rather than alone (Freda, 2002; A.D.A.M. Acromegaly). | ||
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==3D structures of human growth hormone== | ==3D structures of human growth hormone== | ||
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} <br /> | ||
[[3hhr]] - HGH + extracellular domain of its receptor <br /> | |||
[[1huw]], [[1hgu]] – HGH – human <br /> | [[1huw]], [[1hgu]] – HGH – human <br /> | ||
[[3hhr]], [[1hwg]], [[1kf9]] – HGH + HGH receptor<br /> | [[3hhr]], [[1hwg]], [[1kf9]] – HGH + HGH receptor<br /> | ||
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== References == | == References == | ||
<references/> | <references/> | ||
*12. ANDERSON, Lloyd (2012). Nanobiology and physiology of growth hormone secretion. Experimental Biology and Medicine. Experimental biology and medicine. https://doi.org/10.1258/ebm.2011.011306 | |||
*13. Clarence J. Gibbs, Jr., Ph.D., Anthony Joy, D.O., Reid Heffner, M.D., Maryellen Franko, Ph.D., Masayuki Miyazaki, M.D., David M. Asher, M.D., Joseph E. Parisi, M.D., Paul W. Brown, M.D., and D. Carleton Gajdusek, M.D. (1985). Clinical and Pathological Features and Laboratory Confirmation of Creutzfeldt–Jakob Disease in a Recipient of Pituitary-Derived Human Growth Hormone. The New England Journal of Medicine. https://www.nejm.org/doi/pdf/10.1056/NEJM198509193131207 | |||
*14. Orthopedic Institute for Children. Turner Syndrome. Consulted on January 2022. URL : https://www.ortho-institute.org/patient-care/orthopedic-specialties/skeletal-dysplasia-dwarfism/turner-syndrome/ | |||
==See Also== | ==See Also== | ||
* [[Hormone]] | * [[Hormone]] | ||
[[Category:Topic Page]] | [[Category:Topic Page]] | ||