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"
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)
ホルモン

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/09/25 23:40:32」(JST)

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Growth hormone–releasing hormone (GHRH), also known as somatocrinin or by several other names in its endogenous forms and as somatorelin (INN) in its pharmaceutical form, is a releasing hormone of growth hormone (GH). 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]

Nomenclature

Endogenous:
- somatocrinin
- somatoliberin
- growth hormone–releasing hormone (GHRH or GH-RH; HGNC symbol is GHRH)
- growth hormone–releasing factor (GHRF or GRF)
- somatotropin-releasing hormone (SRH)
- somatotropin-releasing factor (SRF)
Pharmaceutical:
- somatorelin (INN)

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,^[2]^[3] stimulating similar pulsatile release of GH. In addition, GHRH also promotes slow-wave sleep directly.^[4] 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

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,^[5] 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,^[6] CJC-1293,^[7] and CJC-1295.^[8]

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.^[9] Tesamorelin,^[10] 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,^[11] and, in 2011, was investigated for effects on certain cognitive tests in the elderly.^[12] 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.^[13]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k GeneGlobe -> GHRH Signaling^{[permanent dead link]} Retrieved on May 31, 2009
^ Plotsky, PM; Vale, W (25 October 1985). "Patterns of growth hormone-releasing factor and somatostatin secretion into the hypophysial-portal circulation of the rat". Science. 230 (4724): 461–3. Bibcode:1985Sci...230..461P. PMID 2864742. doi:10.1126/science.2864742.
^ Frohman, LA; Downs, TR; Clarke, IJ; Thomas, GB (July 1990). "Measurement of growth hormone-releasing hormone and somatostatin in hypothalamic-portal plasma of unanesthetized sheep. Spontaneous secretion and response to insulin-induced hypoglycemia.". The Journal of Clinical Investigation. 86 (1): 17–24. PMC 296684 . PMID 1973173. doi:10.1172/jci114681.
^ Obál F, Krueger J (2001). "The somatotropic axis and sleep.". Rev Neurol (Paris). 157 (11 Pt 2): S12–5. PMID 11924022.
^ Walter F. 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. PMID 15817669. doi:10.1210/en.2004-1286.
^ 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. PMID 16352683. doi:10.1210/jc.2005-1536.
^ 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. PMID 18031173. doi:10.2165/00063030-199912020-00007.
^ Mauss, Stefan; Schmutz, GüNther (2001). "Das HIV-assoziierte Lipodystrophiesyndrom". Medizinische Klinik. 96 (7): 391–401. PMID 11494914. doi:10.1007/PL00002220.
^ "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; 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. 成人における成長ホルモン欠乏症 growth hormone deficiency in adults
3. HIV関連リポジストロフィーの治療 treatment of hiv associated lipodystrophy
4. 先端巨大症の診断 diagnosis of acromegaly
5. Overview of the treatment of castration-resistant prostate cancer (CRPC)

English Journal

Ghrelin acts as energy status sensor of male reproduction by modulating Sertoli cells glycolytic metabolism and mitochondrial bioenergetics.

Martins AD1, Sá R1, Monteiro MP2, Barros A3, Sousa M4, Carvalho RA5, Silva BM6, Oliveira PF7, Alves MG8.
Molecular and cellular endocrinology.Mol Cell Endocrinol.2016 Oct 15;434:199-209. doi: 10.1016/j.mce.2016.07.008. Epub 2016 Jul 5.
Ghrelin is a growth hormone-releasing peptide that has been suggested to interfere with spermatogenesis, though the underling mechanisms remain unknown. We studied the effect of ghrelin in human Sertoli cells (hSCs) metabolic phenotype. For that, hSCs were exposed to increasing concentrations of ghr
PMID 27392494

Effects and safety of combination therapy with gonadotropin-releasing hormone analogue and growth hormone in girls with idiopathic central precocious puberty: a meta-analysis.

Liu S1, Liu Q2, Cheng X1, Luo Y1, Wen Y1.
Journal of endocrinological investigation.J Endocrinol Invest.2016 Oct;39(10):1167-78. doi: 10.1007/s40618-016-0486-9. Epub 2016 May 25.
PURPOSE: This meta-analysis is to evaluate the effects and safety of the combination therapy for girls with idiopathic central precocious puberty (ICPP).METHODS: Electronic databases were searched for randomized controlled trials (RCTs) and clinical controlled trials (CCTs) that adopted gonadotropin
PMID 27225286

Ghrelin suppresses the GnRH-induced preovulatory gonadotropin surge in dairy heifers.

Chouzouris TM1, Dovolou E1, Dafopoulos K2, Georgoulias P3, Vasileiou NG1, Fthenakis GC1, Anifandis G2, Amiridis GS4.
Theriogenology.Theriogenology.2016 Oct 1;86(6):1615-21. doi: 10.1016/j.theriogenology.2016.05.022. Epub 2016 May 27.
Ghrelin, a known growth hormone (GH) secretagogue, alters gonadotropin secretion in many species. Our objectives were to study the effects of ghrelin, on GH, LH, FSH secretion, and on luteal function of the ensuing estrous cycle in cattle. The estrous cycles of eight heifers were synchronized with p
PMID 27329156

Japanese Journal

Investigation of the clinical significance of the growth hormone-releasing peptide-2 test for the diagnosis of secondary adrenal failure

Endocrine Journal 63(6), 533-544, 2016
NAID 130005159562

Effects of retinoic acid on growth hormone-releasing hormone receptor, growth hormone secretagogue receptor gene expression and growth hormone secretion in rat anterior pituitary cells

Endocrine Journal 63(6), 555-561, 2016
NAID 130005159557

Effects of retinoic acid on growth hormone-releasing hormone receptor, growth hormone secretagogue receptor gene expression and growth hormone secretion in rat anterior pituitary cells

Endocrine Journal advpub(0), 2016
NAID 130005143578

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」「GHRH receptor defects」
拡張検索	「ectopic growth hormone-releasing hormone-producing tumor」「growth hormone-releasing hormone neuron」「growth hormone-releasing hormone-producing tumor」「growth hormone-releasing hormone receptor」
関連記事	「grow」「growth」

「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

　　[★]

英: growth hormone-releasing hormone,growth hormone releasing hormone ,GHRH, GRH
同: ソマトトロピン放出ホルモン somatotropin-releasing hormone SRH、ソマトリベリン somatoliberin、成長ホルモン放出因子 growth hormone-releasing factor GRF
関: 成長ホルモン、視床下部ホルモン

「GHRH receptor defects」

　　[★]

同: growth hormone-releasing hormone

「ectopic growth hormone-releasing hormone-producing tumor」

　　[★] 異所性成長ホルモン放出ホルモン産生腫瘍

「growth hormone-releasing hormone neuron」

　　[★] 成長ホルモン放出ホルモンニューロン

「growth hormone-releasing hormone-producing tumor」

　　[★] 成長ホルモン放出ホルモン産生腫瘍

「growth hormone-releasing hormone receptor」

　　[★] 成長ホルモン放出ホルモン受容体

「grow」

　　[★]

v.

(過去: grew-過去分詞: grown)

成長する、生育する、伸びる

関: extend、growth、outgrow、outgrowth、stretch

「growth」

　　[★]

n.

成長

[GeneGlobe-1] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k GeneGlobe -> GHRH Signaling^{[permanent dead link]} Retrieved on May 31, 2009

[2] Plotsky, PM; Vale, W (25 October 1985). "Patterns of growth hormone-releasing factor and somatostatin secretion into the hypophysial-portal circulation of the rat". Science. 230 (4724): 461–3. Bibcode:1985Sci...230..461P. PMID 2864742. doi:10.1126/science.2864742.

[3] Frohman, LA; Downs, TR; Clarke, IJ; Thomas, GB (July 1990). "Measurement of growth hormone-releasing hormone and somatostatin in hypothalamic-portal plasma of unanesthetized sheep. Spontaneous secretion and response to insulin-induced hypoglycemia.". The Journal of Clinical Investigation. 86 (1): 17–24. PMC 296684 . PMID 1973173. doi:10.1172/jci114681.

[4] Obál F, Krueger J (2001). "The somatotropic axis and sleep.". Rev Neurol (Paris). 157 (11 Pt 2): S12–5. PMID 11924022.

[boron-5] Walter F. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 1300. ISBN 1-4160-2328-3.

[6] 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.

[Jette-7] 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. PMID 15817669. doi:10.1210/en.2004-1286.

[8] 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. PMID 16352683. doi:10.1210/jc.2005-1536.

[pmid18031173-9] 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. PMID 18031173. doi:10.2165/00063030-199912020-00007.

[10] Mauss, Stefan; Schmutz, GüNther (2001). "Das HIV-assoziierte Lipodystrophiesyndrom". Medizinische Klinik. 96 (7): 391–401. PMID 11494914. doi:10.1007/PL00002220.

[11] "FDA approves Egrifta to treat Lipodystrophy in HIV patients". U.S. Food and Drug Administration. 2010-11-10. Retrieved 2013-09-13.

[12] Gever, John (2011-07-11). "ICAD: Tesamorelin Boosts Cognition in Elderly". MedPage Today. Retrieved 2013-09-13.

[13] Koh, Benjamin; Hardie, Martin (2013-02-11). "We need an advocate against ASADA’s power in doping control". The Conversation. Retrieved 2013-09-13.

v t e GH/IGF-1 axis signaling modulators
GH (somatotropin)	Agonists: Albusomatropin Bovine somatotropin Efpegsomatropin Growth hormone Human placental lactogen Placental growth hormone (growth hormone variant) Somagrebove Somapacitan Somatosalm Somatotropin Somatropin pegol Somatrem Sometribove Somatrogon (MOD-4023; hGH-CTP) Somavaratan Somavubove Somidobove Antagonists: G120K-hGH Pegvisomant Antisense oligonucleotides: Atesidorsen Binding proteins: GHBP
GHIH (somatostatin)	Agonists: BIM-23052 CH-275 Cortistatin-14 Depreotide Edotreotide Ilatreotide L-803,087 L-817,818 Lanreotide NNC 26-9100 Octreotate Octreotide Pasireotide Pentetreotide RC-160 Seglitide Somatostatin (GHIH) Somatostatin (1-28) SRIF-14 SRIF-28 TT-232 Vapreotide Veldoreotide Antagonists: BIM-23056 Cyclosomatostatin CYN-154806 Satoreotide
GHRH (somatocrinin)	Agonists: Peptide: ALRN-5281 CJC-1295 Dumorelin GHRH Modified GRF (1-29) Rismorelin Sermorelin Somatorelin Tesamorelin Antagonists: MZ-5-156
GHS (ghrelin)	Agonists: Peptide: Alexamorelin Cortistatin-14 EP-51216 Examorelin (hexarelin) Ghrelin GHRP-1 GHRP-3 GHRP-4 GHRP-5 GHRP-6 Ipamorelin Lenomorelin LY-444711 Pralmorelin (GHRP-2) Relamorelin Tabimorelin Ulimorelin; Non-peptide: Adenosine Anamorelin Capromorelin CP-464709 Ibutamoren (MK-677) L-692,585 Macimorelin SM-130686; Unsorted: LY-426410 LY-444711 Antagonists: A-778193 Cortistatin-8 (D-Lys³)-GHRP-6 JMV2959 YIL-781
IGF-1 (somatomedin)	See here instead.
See also: Receptor/signaling modulators • Signaling peptide/protein receptor modulators

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案内

growth hormone-releasing hormone