Growth hormone releasing hormone, somatoliberin, GRF 1-44, somatocrinin or simply GHRH is a hormone ...

1. GRF 1 44
Growth hormone releasing hormone, somatoliberin, GRF 1-44, somatocrinin or simply GHRH is a
hormone that is responsible for accentuating the release of growth hormone from the anterior lobe
of the pituitary gland. GHRH appears in the human hypothalamus during week 18-29 in the
gestation period this corresponds to the initial production of GH in the somatotrophs of the fetus.
Research studies shows that most speciesGRF 1-44 stimulates the biosynthesis and release of GH
from the anterior lobe of the pituitary gland. GRF is synthesized by nerurons, which are located in
the arcuate nucleus of hypothalamus. The hormone is thereafter released into the pituitary gland to
stimulate the GH where it is released in pulses alongside somatostatin. GHRH stimulates the
secretion of GH from the somatotrophs, however endogenous GRF 1-44 has a very short half-life,
however it is released from the hypothalamus, and it travels a short distance to the anterior pituitary
where it exerts its function.
In contrast, the exogenous peptides
that are manufactured synthetically
have undergone numerous chemical
alterations which increases their half
life, bioavailability and mechanism of
action through presentation of more binding sites. The synthetic versions can travel long distances
without being degraded before reaching the somatotrophs where it activates the release of GH.
Recent studies reveal that GRF 1-44 plays a crucial role in promoting slow wave sleep; the GRF 1-44
stimulates GH release by binding to the receptors on the GRFR on the cells. When GHRH binds to
GHRHR (growth hormone releasing hormone receptor) it results in an increased production of GH,
which a cAMP-dependent pathway, however in some cases it, may pass through phospholipase C
pathway among other pathway. The initiation of the cyclic AMP dependent pathway begins with the
changes in receptor conformation, which in turn activates G s alpha subunit, which is a G-protein
complex. This result in the stimulation of adenylyl cyclase, which is membrane, bound and it results
in increased cyclic AMP, which activates PKA allowing the CREB or cyclic AMP response element
binding protein. When CREB undergoes phosphorylation, it enhances the transcription of the GH by
binding the CREs to the cyclic AMP response elements in the promoter side of the gene.
When the hormone production undergoes the phospholipase C pathway, GRF 1-44 stimulates
phospholipase C (PLC) through a beta gamma complex of G-proteins. Activation of PLC results in the
production of diacylglycerol (DAG) and inosital triphosphate IP3. Inosital triphosphate stimulates the
production of calcium ions from endoplasmic reticulum resulting in vesicle fusion and release of
premade growth hormone. When there is an influx of calcium ions, it has a direct action on the cyclic
AMP. The activation of GHRHR conveys the opening of sodium ion channels, which causes
depolarization, and the resultant change opens up the calcium dependent channel allowing the
vesicles to release GH. There are numerous GHRH peptide analogs these include Mod GRF,
Sermorelin among others. All the synthetic versions have been altered to increase their activity
level, bioavailability and prevent degradation as indicated earlier. Moreover, they are more potent
and effective than the endogenously produced hormone. All these synthetic versions are still
undergoing research for safety and use, however none has been approved.