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	==Function and Pathway==		==Function and Pathway==
-		+	The binding of GHRH to its receptor activates the alpha subunit of the associated G-protein complex, stimulating membrane bound adenylyl cyclase and causing an increase in intracellular cAMP concentrations <ref>PMID:12446584</ref>.
	[[Image:GHRH Signaling.jpg]]		[[Image:GHRH Signaling.jpg]]

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Revision as of 03:34, 11 May 2016

Contents 1 Growth Hormone Releasing Hormone 1.1 Introduction 1.1.1 Nomenclature 1.2 Structural Features 1.2.1 Primary Structure 1.2.2 Synthesis 1.3 GHRH Receptor 1.4 Function and Pathway 1.5 Medical Implications 1.6 References

Growth Hormone Releasing Hormone

spinqualitylabelsall models Growth Hormone-Releasing Hormone, modelled using Phyre modelling engine[1] Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Introduction

Growth hormone releasing hormone (GHRH) is a secretory neurohormone that causes growth hormone to be released from the pituitary gland. It is naturally produced in the arcuate nucleus of the hypothalamus. The hormone is produced as a 44 amino acid peptide hormone, and first appears in the hypothalamus between 18 and 29 weeks of gestation, corresponding to the initial production of growth hormone by the fetus ^[1]. Growth hormone is required for normal fetal and post fetal development, including bone growth and the regulation of protein production and the metabolism of lipids and carbohydrates ^[2].

The color key below indicates the N to C directionality of the GHRH protein model to the right.

Amino Terminus

Carboxy Terminus

Nomenclature

Endogenous:

       somatoliberin
       somatocrinin
       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)[3]

Structural Features

Primary Structure

The 44-long amino acid sequence for 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^[3]

Synthesis

GHRH is synthesized by neurons in the arcuate nucleus of the hypothalamus. Axons of the GHRH neurons project to the median eminence, and terminate on the capillaries of the hypothalamic-pituitary portal vessel. GHRH is then carried to the somatotroph cells of the anterior pituitary, where it binds to cause growth hormone release ^[4].

GHRH Receptor

The GHRH receptor gene is expressed in the pituitary as a G-coupled receptor that binds GHRH, resulting in the release of growth hormone ^[5]. Characteristic of G-coupled type receptors, the GHRH receptor has 7 membrane spanning portions. The gene coding for GHRHR is found on chromosome 7 ^[6]. The figure below and to the left is a model of the extracellular domain of the GHRH receptor. The figure below and to the right shows the extracellular and membrane spanning sections of the GHRH receptor, with possible single nucleotide points of mutation indicated by the letters T and P.

spinqualitylabelsall models GHRH Receptor Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

^[7]

Function and Pathway

The binding of GHRH to its receptor activates the alpha subunit of the associated G-protein complex, stimulating membrane bound adenylyl cyclase and causing an increase in intracellular cAMP concentrations ^[8].

This image shows the signalling pathway of GHRH causing the release of growth hormone ^[6]

Medical Implications

References

1. ↑ Chawla RK, Parks JS, Rudman D. Structural variants of human growth hormone: biochemical, genetic, and clinical aspects. Annu Rev Med. 1983;34:519-47. PMID:6344776 doi:http://dx.doi.org/10.1146/annurev.me.34.020183.002511
2. ↑ Tang SS, Zhang JH, Du MH, Wu J, Liu JJ. Construction and activity of a novel GHRH analog, Pro-Pro-hGHRH(1-44)-Gly-Gly-Cys. Acta Pharmacol Sin. 2004 Nov;25(11):1464-70. PMID:15525469
3. ↑ ^{3.0 3.1} https://en.wikipedia.org/wiki/Growth_hormone%E2%80%93releasing_hormone
4. ↑ Lin-Su K, Wajnrajch MP. Growth Hormone Releasing Hormone (GHRH) and the GHRH Receptor. Rev Endocr Metab Disord. 2002 Dec;3(4):313-23. PMID:12424433
5. ↑ Gaylinn BD. Molecular and cell biology of the growth hormone-releasing hormone receptor. Growth Horm IGF Res. 1999 Apr;9 Suppl A:37-44. PMID:10429879
6. ↑ ^{6.0 6.1} https://www.qiagen.com/us/shop/genes-and-pathways/pathway-details?pwid=199
7. ↑ http://synapse.koreamed.org/DOIx.php?id=10.3803/jkes.2006.21.3.173&vmode=PUBREADER#!po=25.0000
8. ↑ Cunha SR, Mayo KE. Ghrelin and growth hormone (GH) secretagogues potentiate GH-releasing hormone (GHRH)-induced cyclic adenosine 3',5'-monophosphate production in cells expressing transfected GHRH and GH secretagogue receptors. Endocrinology. 2002 Dec;143(12):4570-82. PMID:12446584 doi:http://dx.doi.org/10.1210/en.2002-220670