Growth hormone–releasing hormone

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Growth hormone releasing hormone
)
Growth hormone releasing hormone
Identifiers
SymbolGHRH
Alt. symbolsGRF, GHRF
Chr. 20 p12 or q11.2-q12
Search for
StructuresSwiss-model
DomainsInterPro

Growth hormone–releasing hormone (GHRH), also known as somatocrinin or by

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:
    • INN
      )

Origin

GHRH is released from neurosecretory nerve terminals of these arcuate neurons, and is carried by the hypothalamo-

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

Main article:
Growth hormone-releasing hormone receptor

The GHRHR is a member of the

kD.[1]

Signal transduction

GHRH binding to GHRHR results in increased GH production mainly by the

phospholipase C pathway (IP3/DAG pathway),[1] and other minor pathways.[1]

The

promoter region of the GH gene. It also increases transcription of the GHRHR gene, providing positive feedback.[1]

In the

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

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-hypophyseal 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.[6]

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,[7] CJC-1293,[8] and CJC-1295.[9]

Many GHRH analogs remain primarily

highly active antiretroviral therapy,[12] and, in 2011, was investigated for effects on certain cognitive tests in the elderly.[13] 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.[14]

See also

References

  1. ^ a b c d e f g h i j k GeneGlobe -> GHRH Signaling Archived 2020-10-09 at the Wayback Machine Retrieved on October 5, 2020
  2. PMID 2864742
    .
  3. PMID 1973173
    .
  4. PMID 11924022
    .
  5. ISBN 1-4160-2328-3
    .
  6. PMID 32644973
    .
  7. PMID 15525469
    .
  8. PMID 15817669
    .
  9. PMID 16352683
    .
  10. S2CID 195690081
    .
  11. S2CID 27548912
    .
  12. ^ "FDA approves Egrifta to treat Lipodystrophy in HIV patients". U.S. Food and Drug Administration. 2010-11-10. Retrieved 2013-09-13.
  13. ^ Gever J (2011-07-11). "ICAD: Tesamorelin Boosts Cognition in Elderly". MedPage Today. Retrieved 2013-09-13.
  14. ^ Koh B, Hardie M (2013-02-11). "We need an advocate against ASADA's power in doping control". The Conversation. Retrieved 2013-09-13.
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