WordNet

cultivate by growing, often involving improvements by means of agricultural techniques; "The Bordeaux region produces great red wines"; "They produce good ham in Parma"; "We grow wheat here"; "We raise hogs here" (同)raise, farm, produce
come to have or undergo a change of (physical features and attributes); "He grew a beard"; "The patient developed abdominal pains"; "I got funny spots all over my body"; "Well-developed breasts" (同)develop, produce, get, acquire
become attached by or as if by the process of growth; "The tree trunks had grown together"
become larger, greater, or bigger; expand or gain; "The problem grew too large for me"; "Her business grew fast"
cause to grow or develop; "He grows vegetables in his backyard"
increase in size by natural process; "Corn doesnt grow here"; "In these forests, mushrooms grow under the trees"; "her hair doesnt grow much anymore"
(biology) the process of an individual organism growing organically; a purely biological unfolding of events involved in an organism changing gradually from a simple to a more complex level; "he proposed an indicator of osseous development in children" (同)growing, maturation, development, ontogeny, ontogenesis
(pathology) an abnormal proliferation of tissue (as in a tumor)
a progression from simpler to more complex forms; "the growth of culture"
something grown or growing; "a growth of hair"
vegetation that has grown; "a growth of trees"; "the only growth was some salt grass"
be a contributing factor; "make things factor into a companys profitability"
any of the numbers (or symbols) that form a product when multiplied together
an independent variable in statistics
anything that contributes causally to a result; "a number of factors determined the outcome"
consider as relevant when making a decision; "You must factor in the recent developments" (同)factor in, factor out
resolve into factors; "a quantum computer can factor the number 15" (同)factor in, factor out
an event known to have happened or something known to have existed; "your fears have no basis in fact"; "how much of the story is fact and how much fiction is hard to tell"
a concept whose truth can be proved; "scientific hypotheses are not facts"
a piece of information about circumstances that exist or events that have occurred; "first you must collect all the facts of the case"
a statement or assertion of verified information about something that is the case or has happened; "he supported his argument with an impressive array of facts"
the secretion of an endocrine gland that is transmitted by the blood to the tissue on which it has a specific effect (同)endocrine, internal_secretion

PrepTutorEJDIC

『成長する』,育つ,〈植物が〉生える,茂る / (類・量・程などにおいて)『増大する』,大きくなる / 『しだいになる』 / …‘を'成長させる,大きくする,育てる / …から生じる(起こる)
〈U〉(…の)『成長』,発育;『発達』,発展《+『of』+『名』》 / 〈U〉(数・量,重要性・力などの)『増加』,増大,拡張《+『of』+『名』》 / 〈U〉《修飾語[句]を伴って》栽培,生産,…産 / 〈C〉成育した物,(草,木,髪,ひげなどの)生えたもの / 〈C〉腫瘍(しゅよう)
(…の)『要因』,(…を生み出す)要素《+『in』+『名』(do『ing』)》 / 囲数,約数 / 代理人,《おもに英》仲買人 / =factorize
〈C〉『事実』,実際にある(あった)事 / 〈U〉真相,真実(truth) / 《the~》(法律用語で)犯行
ホルモン

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/04/30 21:31:53」(JST)

wiki en

Growth-hormone-releasing hormone (GHRH), also known as growth-hormone-releasing factor (GRF, GHRF), somatoliberin or somatocrinin, is a releasing hormone for growth hormone. It is a 44^[1]-amino acid peptide hormone produced in the arcuate nucleus of the hypothalamus.

GHRH first appears in the human hypothalamus between 18 and 29 weeks of gestation, which corresponds to the start of production of growth hormone and other somatotropes in fetuses.^[1]

Origin

GHRH is released from neurosecretory nerve terminals of these arcuate neurons, and is carried by the hypothalamo-hypophyseal portal system to the anterior pituitary gland, where it stimulates growth hormone (GH) secretion by stimulating the growth hormone-releasing hormone receptor. GHRH is released in a pulsatile manner, stimulating similar pulsatile release of GH. In addition, GHRH also promotes slow-wave sleep directly.^[2] Growth hormone is required for normal postnatal growth, bone growth, regulatory effects on protein, carbohydrate, and lipid metabolism.^[1]

Effect

GHRH stimulates GH production and release by binding to the GHRH Receptor (GHRHR) on cells in the anterior pituitary.

Receptor

Main article: Growth hormone-releasing hormone receptor

The GHRHR is a member of the secretin family of G protein-coupled receptors, and is located on chromosome 7. This protein is transmembranous with seven folds, and its molecular weight is approximately 44 kD.^[1]

Signal transduction

GHRH binding to GHRHR results in increased GH production mainly by the cAMP-dependent pathway,^[3] but also by the phospholipase C pathway (IP₃/DAG pathway),^[1] and other minor pathways.^[1]

The cAMP-dependent pathway is initiated by the binding of GHRH to its receptor, causing receptor conformation that activates G_s alpha subunit of the closely associated G-Protein complex on the intracellular side. This results in stimulation of membrane-bound adenylyl cyclase and increased intracellular cyclic adenosine monophosphate (cAMP). cAMP binds to and activates the regulatory subunits of protein kinase A (PKA), allowing the free catalytic subunits to translocate to the nucleus and phosphorylate the transcription factor cAMP response element-binding protein (CREB). Phosphorylated CREB, together with its coactivators, p300 and CREB-binding protein (CBP) enhances the transcription of GH by binding to CREs cAMP-response elements in the promoter region of the GH gene. It also increases transcription of the GHRHR gene, providing positive feedback.^[1]

In the phospholipase C pathway, GHRH stimulates phospholipase C (PLC) through the βγ-complex of heterotrimeric G-proteins. PLC activation produces both diacylglycerol (DAG) and inositol triphosphate (IP₃), the latter leading to release of intracellular Ca²⁺ from the endoplasmic reticulum, increasing cytosolic Ca²⁺ concentration, resulting in vesicle fusion and release of secretory vesicles containing premade growth hormone.^[1]

Some Ca²⁺ influx is also a direct action of cAMP, which is distinct from the usual cAMP-dependent pathway of activating protein kinase A.^[1]

Activation of GHRHRs by GHRH also conveys opening of Na+ channels by phosphatidylinositol 4,5-bisphosphate, causing cell depolarization. The resultant change in the intracellular voltage opens a voltage-dependent calcium channel, resulting in vesicle fusion and release of GH.^[1]

Relationship of GHRH and somatostatin

The actions of GHRH are opposed by somatostatin (growth-hormone-inhibiting hormone). Somatostatin is released from neurosecretory nerve terminals of periventricular somatostatin neurons, and is carried by the hypothalamo-hypophysial portal circulation to the anterior pituitary where it inhibits GH secretion. Somatostatin and GHRH are secreted in alternation, giving rise to the markedly pulsatile secretion of GH.

Other functions

GHRH expression has been demonstrated in peripheral cells and tissues outside its main site in the hypothalamus, for example, in the pancreas, epithelial mucosa of the gastrointestinal tract and, pathologically, in tumour cells.^[1]

Sequence

The amino acid sequence (44 long) of human GHRH is:

HO - Tyr - Ala - Asp - Ala - Ile - Phe - Thr - Asn - Ser - Tyr - Arg - Lys - Val - Leu - Gly - Gln - Leu - Ser - Ala - Arg - Lys - Leu - Leu - Gln - Asp - Ile - Met - Ser - Arg - Gln - Gln - Gly - Glu - Ser - Asn - Gln - Glu - Arg - Gly - Ala - Arg - Ala - Arg - Leu - NH₂

Analogs

Growth-hormone-releasing hormone is the lead compound for a number of structural and functional analogs, such as Pro-Pro-hGHRH(1-44)-Gly-Gly-Cys,^[4] CJC-1293,^[5] and CJC-1295.^[6]

Many GHRH analogs remain primarily research chemicals, although some have specific applications. Sermorelin, a functional peptide fragment of GHRH, has been used in the diagnosis of deficiencies in growth hormone secretion.^[7] Tesamorelin,^[8] under the trade name Egrifta, received U.S. Food and Drug Administration approval in 2010 for the treatment of lipodystrophy in HIV patients under highly active antiretroviral therapy,^[9] and, in 2011, was investigated for effects on certain cognitive tests in the elderly.^[10] As a category, the use of GHRH analogs by professional athletes may be prohibited by restrictions on doping in sport because they act as growth hormone secretagogues.^[11]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k GeneGlobe -> GHRH Signaling Retrieved on May 31, 2009
^ Obál F, Krueger J (2001). "The somatotropic axis and sleep.". Rev Neurol (Paris) 157 (11 Pt 2): S12–5. PMID 11924022.
^ Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 1300. ISBN 1-4160-2328-3.
^ Tang SS, Zhang JH, Du MH, Wu J, Liu JJ (2004). "Construction and activity of a novel GHRH analog, Pro-Pro-hGHRH(1-44)-Gly-Gly-Cys.". Acta Pharmacol. Sin. 25 (11): 1464–70. PMID 15525469.
^ Jetté L, Léger R, Thibaudeau K, Benquet C, Robitaille M, Pellerin I, Paradis V, van Wyk P, Pham K, Bridon DP (2005). "Human Growth Hormone-Releasing Factor (hGRF)1–29-Albumin Bioconjugates Activate the GRF Receptor on the Anterior Pituitary in Rats: Identification of CJC-1295 as a Long-Lasting GRF Analog". Endocrinology 146 (7): 3052–8. doi:10.1210/en.2004-1286. PMID 15817669.
^ 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.
^ 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 : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy 12 (2): 139–57. PMID 18031173.
^ Mauss, Stefan; Schmutz, GüNther (2001). "Das HIV-assoziierte Lipodystrophiesyndrom". Medizinische Klinik 96 (7): 391–401. doi:10.1007/PL00002220. PMID 11494914.
^ "FDA approves Egrifta to treat Lipodystrophy in HIV patients". U.S. Food and Drug Administration. 2010-11-10. Retrieved 2013-09-13.
^ Gever, John (2011-07-11). "ICAD: Tesamorelin Boosts Cognition in Elderly". MedPage Today. Retrieved 2013-09-13.
^ Koh, Benjamin and Hardie, Martin (2013-02-11). "We need an advocate against ASADA’s power in doping control". The Conversation. Retrieved 2013-09-13.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 成長ホルモンの生理学 physiology of growth hormone
2. HIV関連リポジストロフィーの治療 treatment of hiv associated lipodystrophy
3. 先端巨大症の診断 diagnosis of acromegaly
4. グレリン ghrelin
5. 先端巨大症の原因および臨床症状 causes and clinical manifestations of acromegaly

English Journal

Ghrelin modulates sympathetic nervous system activity and stress response in lean and overweight men.

Lambert E, Lambert G, Ika-Sari C, Dawood T, Lee K, Chopra R, Straznicky N, Eikelis N, Drew S, Tilbrook A, Dixon J, Esler M, Schlaich MP.SourceHuman Neurotransmitters Laboratory, Baker IDI Heart & Diabetes Institute, PO Box 6492, St Kilda Road Central, Melbourne, Victoria 8008, Australia. Elisabeth.lambert@bakeridi.edu.au.
Hypertension.Hypertension.2011 Jul;58(1):43-50. Epub 2011 Apr 18.
Ghrelin is a growth hormone-releasing peptide secreted by the stomach with potent effects on appetite. Experimental and clinical studies indicate that ghrelin also influences cardiovascular regulation and metabolic function and mediates behavioral responses to stress. We investigated the effects of
PMID 21502567

The Locus Ceruleus Responds to Signaling Molecules Obtained from the CSF by Transfer through Tanycytes.

Feng CY, Wiggins LM, von Bartheld CS.SourceDepartment of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557.
The Journal of neuroscience : the official journal of the Society for Neuroscience.J Neurosci.2011 Jun 22;31(25):9147-58.
Neurons can access signaling molecules through two principal pathways: synaptic transmission ("wiring transmission") and nonsynaptic transmission ("volume transmission"). Wiring transmission is usually considered the far more important mode of neuronal signaling. Using embryonic chick locus ceruleus
PMID 21697366

Japanese Journal

Growth Hormone Releasing Peptide-2, a Ghrelin Agonist, Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Rats

LI Guang,LI Jianguo,ZHOU Qing,SONG Xuemin,LIANG Hui,HUANG Lili
Tohoku journal of experimental medicine 222(1), 7-13, 2010-09-01
NAID 10027085494

下垂体腺腫におけるGsα遺伝子変異の検討

大竹啓之,三木伸泰,小野昌美,堀智勝,高野加寿恵
東京女子医科大学雑誌 77(5), 256-263, 2007-05
… Activating mutations of the Gsα protein coupled to the growth hormone-releasing hormone (GRH) receptor contribute to the genesis of growth hormone (GH)-secreting pituitary adenomas. …
NAID 110007525243

Related Pictures

★リンクテーブル★

リンク元	「成長ホルモン放出ホルモン」「GRF」
関連記事	「grow」「fact」「factor」「growth」「releasing factor」

「成長ホルモン放出ホルモン」

Growth hormone releasing hormone
Identifiers
Symbol	GHRH
Alt. symbols	GRF, GHRF
CAS number	9034-39-3
Entrez	2691
HUGO	4265
OMIM	139190
RefSeq	NM_021081
UniProt	P01286
Other data
Locus	Chr. 20 p12 or q11.2-q12