Modified GRF, or Modgrf, is a shortened form of the growth-hormone releasing hormone (GHRH). GHRH is also known as the GH-releasing factor, or GRF. GRF is released from the hypothalamus to bind GHRH receptors (GHRH-R) in the pituitary gland, which results in the release of GH¹. modGRF is made up of 29 amino acids (1-29), whereas full GRF possesses 44. Some studies on the structure of modGRF indicate that amino acids 13-21 alone are essential for GHRH-R binding, as deleting amino acids outside this region decreased receptor affinity by a maximum of 5%, whereas deletion or substitution within the 13-21 chain decreased affinity to less than 1%². On the other hand, the alteration of either terminus also had a deleterious effect on GHRH-R affinity². modGRF may also be termed sermorelin. Treatment with a form of modGRF resulted in a four-fold increase in GH release in an in vitro study using rat pituitary cells in culture³. This peptide may have beneficial roles in animal growth, fat metabolism and hormonal regulation. It may also modulate IGF1 activity, due to its effects on GH¹. This implies another role for modGRF in immune system regulation¹. Based on its physiological and biochemical properties, modGRF is regarded as a viable experimental, and also possibly therapeutic, agent. 

Experimental uses of modGRF

GRF may also instigate pain relief in response to inflammation, due to its actions on pituitary receptors. An animal study demonstrated the hormone's effects on a rat model of this (i.e. endotoxin-induced hyperalgesia). Rats treated with intraperitoneal GRF 300 minutes before experimental endotoxin administration exhibited reduced, dose-dependent thermal and mechanical hyperalgesia⁴. Despite this, GRF may not have significant effects on the concentrations of pro-inflammatory biomarkers such as NFkappaB, interleukins or TNFalpha⁴. There is some evidence that GHRH activation results in the recruitment of immune-system cells. This receptor may also play a role in the promotion of granulocyte proliferation⁵. modGRF is also associated with the release of histamine in rodent mast cell culture studies⁶. 

GHRH-R Activation and its Role in Disease

The receptor for GRF and its analogs, GHRH-R, has been observed as being overexpressed on many cancer cell lines⁷. GRF may also promote the expression of epidermal growth factor-type receptors on murine prostate cancer cell lines⁸. Its receptors may also play a role in the progression and proliferation of the cells associated with atypical, treatment-resistant breast cancer types⁹. GHRH-R activation may also promote general cell proliferation and impair normal cellular apoptosis^1,10. modGRF also significantly increased the concentrations of vascular endothelial growth factor (VEGF), a marker of potential neovascularization (or new blood vessel growth) in an in vitro study¹¹. These properties may be exploited by tumors in order to enhance survival and avoid cell death. Therefore, modGRF may be used to validate the effects of emerging GHRH-R antagonists currently proposed as anticancer drugs. An example of these demonstrated the ability to significantly inhibit the growth of prostate cancer cells grafted onto nude mice¹⁰. On the other hand, the inhibition of GHRH-R was shown to have a negative effect in a mouse model of acetaminophen-induced liver damage¹².

References:

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3. Jette L, Leger R, Thibaudeau K, et al. 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. 2005;146(7):3052-3058.
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11. Stepien T, Sacewicz M, Lawnicka H, et al. Stimulatory effect of growth hormone-releasing hormone (GHRH(1-29)NH2) on the proliferation, VEGF and chromogranin A secretion by human neuroendocrine tumor cell line NCI-H727 in vitro. Neuropeptides. 2009;43(5):397-400.
12. Wang T, Hai J, Chen X, et al. Inhibition of GHRH aggravated acetaminophen-induced acute mice liver injury through GH/IGF-I axis. Endocrine journal. 2012;59(7):579-587.