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

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/12/04 15:14:03」(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

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. 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 : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy 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.
^ "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. 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. 慢性腎疾患における成長ホルモン代謝 growth hormone metabolism in chronic kidney disease
5. 先端巨大症の診断 diagnosis of acromegaly

English Journal

Androgen Receptor Coactivators in Regulation of Growth and Differentiation in Prostate Cancer.

Culig Z1.
Journal of cellular physiology.J Cell Physiol.2016 Feb;231(2):270-4. doi: 10.1002/jcp.25099.
Androgen receptor (AR) is a key factor in regulation of growth and differentiation in normal and malignant prostate. Endocrine therapies for prostate cancer include inhibition of androgen production either by analogs of luteinizing hormone releasing hormone or abiraterone acetate and/or use of anti-
PMID 26201947

Recent advances in central congenital hypothyroidism.

Schoenmakers N1, Alatzoglou KS2, Chatterjee VK2, Dattani MT2.
The Journal of endocrinology.J Endocrinol.2015 Dec;227(3):R51-71. doi: 10.1530/JOE-15-0341. Epub 2015 Sep 28.
Central congenital hypothyroidism (CCH) may occur in isolation, or more frequently in combination with additional pituitary hormone deficits with or without associated extrapituitary abnormalities. Although uncommon, it may be more prevalent than previously thought, affecting up to 1:16 000 neonat
PMID 26416826

Effect of Deletion of Ghrelin-O-Acyltransferase on the Pulsatile Release of Growth Hormone in Mice.

Xie TY1, Ngo ST1,2,3, Veldhuis JD4, Jeffery PL5, Chopin LK5, Tschöp M6, Waters MJ7, Tolle V8, Epelbaum J8, Chen C1, Steyn FJ1,3.
Journal of neuroendocrinology.J Neuroendocrinol.2015 Dec;27(12):872-86. doi: 10.1111/jne.12327.
Ghrelin, a gut hormone originating from the post-translational cleavage of preproghrelin, is the endogenous ligand of growth hormone secretagogue receptor 1a (GHS-R1a). Within the growth hormone (GH) axis, the biological activity of ghrelin requires octanoylation by ghrelin-O-acyltransferase (GOAT),
PMID 26442444

Japanese Journal

Current Perspective : Desensitization by Different Strategies of Epidermal Growth Factor Receptor and ErbB4

Yamamoto Hideyuki,Higa-Nakamine Sayomi,Noguchi Nobuhiro [他]
Journal of pharmacological sciences 124(3), 287-293, 2014-03
NAID 40020026267

Adult Growth Hormone Deficiency: Current Concepts

FUKUDA Izumi,HIZUKA Naomi,MURAOKA Toko,ICHIHARA Atsuhiro
Neurologia medico-chirurgica, 2014
… The clinical syndrome of adult growth hormone deficiency (AGHD) was widely recognized in the 1980s. … In this review, we first describe the clinical features and diagnosis of AGHD and then state the effects of growth hormone (GH) therapy for these patients. …
NAID 130004678071

下垂体腺腫の最前線

松野彰
Neuro-Oncologyの進歩 21(1), 29-39, 2014
… Growth hormone-releasing hormone expression in somatotroph adenomas, and corticotropin-releasing hormone expression in corticotroph adenomas have been demonstrated. …
NAID 130004648362

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」
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」「growth hormone-releasing hormone」
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