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Growth hormone (GH) or somatotropin, also known as human growth hormone in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in human development. GH also stimulates production of insulin-like growth factor 1 (IGF-1) and increases the concentration of glucose and free fatty acids. It is a type of mitogen which is specific only to the receptors on certain types of cells. GH is a 191-amino acid, single-chain polypeptide that is synthesized, stored and secreted by somatotropic cells within the lateral wings of the anterior pituitary gland.
The arcuate nucleus of the hypothalamus (ARH), or ARC, is also known as the infundibular nucleus to distinguish it from the arcuate nucleus of the medulla oblongata in the brainstem. The arcuate nucleus is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence. The arcuate nucleus includes several important and diverse populations of neurons that help mediate different neuroendocrine and physiological functions, including neuroendocrine neurons, centrally projecting neurons, and astrocytes. The populations of neurons found in the arcuate nucleus are based on the hormones they secrete or interact with and are responsible for hypothalamic function, such as regulating hormones released from the pituitary gland or secreting their own hormones. Neurons in this region are also responsible for integrating information and providing inputs to other nuclei in the hypothalamus or inputs to areas outside this region of the brain. These neurons, generated from the ventral part of the periventricular epithelium during embryonic development, locate dorsally in the hypothalamus, becoming part of the ventromedial hypothalamic region. The function of the arcuate nucleus relies on its diversity of neurons, but its central role is involved in homeostasis. The arcuate nucleus provides many physiological roles involved in feeding, metabolism, fertility, and cardiovascular regulation.
Ghrelin is a hormone primarily produced by enteroendocrine cells of the gastrointestinal tract, especially the stomach, and is often called a "hunger hormone" because it increases the drive to eat. Blood levels of ghrelin are highest before meals when hungry, returning to lower levels after mealtimes. Ghrelin may help prepare for food intake by increasing gastric motility and stimulating the secretion of gastric acid.
Motilin is a 22-amino acid polypeptide hormone in the motilin family that, in humans, is encoded by the MLN gene.
Growth hormone–releasing hormone (GHRH), also known as somatocrinin among other names in its endogenous form and as somatorelin (INN) in its pharmaceutical form, is a releasing hormone of growth hormone (GH). It is a 44-amino acid peptide hormone produced in the arcuate nucleus of the hypothalamus.
Growth hormone secretagogue receptor(GHS-R), also known as ghrelin receptor, is a G protein-coupled receptor that binds growth hormone secretagogues (GHSs), such as ghrelin, the "hunger hormone". The role of GHS-R is thought to be in regulating energy homeostasis and body weight. In the brain, they are most highly expressed in the hypothalamus, specifically the ventromedial nucleus and arcuate nucleus. GSH-Rs are also expressed in other areas of the brain, including the ventral tegmental area, hippocampus, and substantia nigra. Outside the central nervous system, too, GSH-Rs are also found in the liver, in skeletal muscle, and even in the heart.
Growth hormone-releasing peptide 6 (GHRP-6), also known as growth hormone-releasing hexapeptide, is one of several synthetic met-enkephalin analogues that include unnatural D-amino acids, were developed for their growth hormone-releasing activity and are called growth hormone secretagogues. They lack opioid activity but are potent stimulators of growth hormone (GH) release. These secretagogues are distinct from growth hormone releasing hormone (GHRH) in that they share no sequence relation and derive their function through activation of a completely different receptor. This receptor was originally called the growth hormone secretagogue receptor (GHSR), but due to subsequent discoveries, the hormone ghrelin is now considered the receptor's natural endogenous ligand, and it has been renamed as the ghrelin receptor. Therefore, these GHSR agonists act as synthetic ghrelin mimetics.
The growth-hormone-releasing hormone receptor (GHRHR) is a G-protein-coupled receptor that binds growth hormone-releasing hormone. The GHRHR activates a Gs protein that causes a cascade of cAMP via adenylate cyclase. GHRHR is distinct from the growth hormone secretagogue receptor, where growth hormone releasing peptides act to release growth hormone.
CJC-1295, also known as DAC:GRF, is a synthetic analogue of growth hormone-releasing hormone (GHRH) and a growth hormone secretagogue (GHS) which was developed by ConjuChem Biotechnologies. It is a modified form of GHRH (1-29) with improved pharmacokinetics, especially in regard to half-life.
Ibutamoren is a potent, long-acting, orally-active, selective, and non-peptide agonist of the ghrelin receptor and a growth hormone secretagogue, mimicking the growth hormone (GH)-stimulating action of the endogenous hormone ghrelin. It has been shown to increase the secretion of several hormones including GH and insulin-like growth factor 1 (IGF-1) and produces sustained increases in the plasma levels of these hormones without affecting cortisol levels.
Tabimorelin (INN) is a drug which acts as a potent, orally-active agonist of the ghrelin/growth hormone secretagogue receptor (GHSR) and growth hormone secretagogue, mimicking the effects of the endogenous peptide agonist ghrelin as a stimulator of growth hormone (GH) release. It was one of the first GH secretagogues developed and is largely a modified polypeptide, but it is nevertheless orally-active in vivo. Tabimorelin produced sustained increases in levels of GH and insulin-like growth factor 1 (IGF-1), along with smaller transient increases in levels of other hormones such as adrenocorticotropic hormone (ACTH), cortisol, and prolactin. However actual clinical effects in adults with growth hormone deficiency were limited, with only the most severely GH-deficient patients showing significant benefit, and tabimorelin was also found to act as a CYP3A4 inhibitor which could cause it to have undesirable interactions with other drugs.
Cyril Y. Bowers, M.D., emeritus professor of medicine at Tulane University School of Medicine, attended medical school at the University of Oregon and did an internship at the University of Washington. He then studied biochemistry at Cornell University and attended the postgraduate school of medicine at the University of Pennsylvania. From 1961-2004 he was the director of the Section of Endocrinology & Metabolism in the department of medicine at Tulane University School of Medicine. Bowers has served on the editorial board of several endocrine journals, was a member of the National Institute of Diabetes and Digestive and Kidney Diseases Study Section for eight years and has written over 400 articles in peer-reviewed journals, including chapters in books and over 200 abstracts.
Modified GRF (1-29) often abbreviated as mod GRF (1-29), originally known as tetrasubstituted GRF (1-29), is a term used to identify a 29 amino acid peptide analogue of growth-hormone-releasing hormone (GHRH), a releasing hormone of growth hormone (GH). It is a modified version of the shortest fully functional fragment of GHRH, often referred to as growth hormone releasing factor (1-29), and also known by its standardized name, sermorelin.
Tesamorelin (INN) is a synthetic form of growth-hormone-releasing hormone (GHRH) which is used in the treatment of HIV-associated lipodystrophy, approved initially in 2010. It is produced and developed by Theratechnologies, Inc. of Canada. The drug is a synthetic peptide consisting of all 44 amino acids of human GHRH with the addition of a trans-3-hexenoic acid group.
Macimorelin (INN) – or Macrilen – is a drug that was developed by Aeterna Zentaris for use in the diagnosis of adult growth hormone deficiency. Macimorelin acetate, the salt formulation, is a synthetic growth hormone secretagogue receptor agonist. It is a growth hormone secretagogue receptor agonist, causing release of growth hormone from the pituitary gland. Macimorelin acetate is described chemically as D-Tryptophanamide, 2-methylalanyl-N-[(1R)-1-(formylamino)-2-(1H-indol-3-yl)ethyl]-acetate.
Pralmorelin (INN), also known as pralmorelin hydrochloride (JAN) and pralmorelin dihydrochloride (USAN), as well as, notably, growth hormone-releasing peptide 2 (GHRP-2), is a growth hormone secretagogue (GHS) used as a diagnostic agent that is marketed by Kaken Pharmaceutical in Japan in a single-dose formulation for the assessment of growth hormone deficiency (GHD).
Ipamorelin (INN) (developmental code name NNC 26-0161) is a peptide selective agonist of the ghrelin/growth hormone secretagogue receptor (GHS) and a growth hormone secretagogue. It is a pentapeptide with the amino acid sequence Aib-His-D-2-Nal-D-Phe-Lys-NH2 that was derived from GHRP-1.
Examorelin (INN) (developmental code names EP-23905, MF-6003), also known as hexarelin, is a potent, synthetic, peptidic, orally-active, centrally-penetrant, and highly selective agonist of the ghrelin/growth hormone secretagogue receptor (GHSR) and a growth hormone secretagogue which was developed by Mediolanum Farmaceutici. It is a hexapeptide with the amino acid sequence His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2 which was derived from GHRP-6. These GH-releasing peptides have no sequence similarity to ghrelin, but mimic ghrelin by acting as agonists at the ghrelin receptor.
The hypothalamic–pituitary–somatotropic axis, or hypothalamic–pituitary–somatic axis, also known as the hypothalamic–pituitary–growth axis, is a hypothalamic–pituitary axis which includes the secretion of growth hormone from the somatotropes of the pituitary gland into the circulation and the subsequent stimulation of insulin-like growth factor 1 production by GH in tissues such as, namely, the liver. Other hypothalamic–pituitary hormones such as growth hormone-releasing hormone, growth hormone-inhibiting hormone, and ghrelin (GHS) are involved in the control of GH secretion from the pituitary gland. The HPS axis is involved in postnatal human growth. Individuals with growth hormone deficiency or Laron syndrome show symptoms like short stature, dwarfism and obesity, but are also protected from some forms of cancer. Conversely, acromegaly and gigantism are conditions of GH and IGF-1 excess usually due to a pituitary tumor, and are characterized by overgrowth and tall stature.
References
- 1 2 Davenport AP, Bonner TI, Foord SM, Harmar AJ, Neubig RR, Pin JP, et al. (December 2005). "International Union of Pharmacology. LVI. Ghrelin receptor nomenclature, distribution, and function". Pharmacological Reviews. 57 (4): 541–6. doi:10.1124/pr.57.4.1. PMID 16382107. S2CID 11254096.
- ↑ Camanni F, Ghigo E, Arvat E (January 1998). "Growth hormone-releasing peptides and their analogs". Frontiers in Neuroendocrinology. 19 (1): 47–72. doi:10.1006/frne.1997.0158. PMID 9465289. S2CID 31400577.
- ↑ Teichman, SL; et al. (2006). "Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults". J Clin Endocrinol Metab. 91 (3): 799–805. doi: 10.1210/jc.2005-1536 . PMID 16352683.
- ↑ Prakash A, Goa KL (August 1999). "Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency". BioDrugs. 12 (2): 139–57. doi:10.2165/00063030-199912020-00007. PMID 18031173.
- ↑ Mauss, Stefan; Schmutz, Günther (2001). "Das HIV-assoziierte Lipodystrophiesyndrom". Medizinische Klinik. 96 (7): 391–401. doi:10.1007/PL00002220. PMID 11494914.
- ↑ Mutschler, Ernst (2013). Arzneimittelwirkungen (in German) (10 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. p. 353. ISBN 978-3-8047-2898-1.
- ↑ Alexopoulou O, Abs R, Maiter D (2010). "Treatment of adult growth hormone deficiency: who, why and how? A review". Acta Clin Belg. 65 (1): 13–22. doi:10.1179/acb.2010.002. PMID 20373593. S2CID 24874132.
- ↑ Fraser GL, Hoveyda HR, Tannenbaum GS (2008). "Pharmacological demarcation of the growth hormone, gut motility and feeding effects of ghrelin using a novel ghrelin receptor agonist". Endocrinology. 149 (12): 6280–8. doi: 10.1210/en.2008-0804 . PMID 18719021.
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