GHRH (Somatorelin) description
Growth hormone–releasing hormone (GHRH, Somatocrinin, Somatorelin) is a 44-amino acid peptide hormone produced in the arcuate nucleus of the hypothalamus. GHRH is released from the neurosecretory nerve terminals of arcuate neurons and is transmitted through the hypothalamic-pituitary portal system to the anterior pituitary, where it stimulates growth hormone secretion by stimulating the growth hormone-releasing hormone receptor. Growth hormone–releasing hormone is released in a pulsating manner, thereby stimulating the pulsating release of growth hormone.
GHRH and its receptors
GHRH and its receptors are expressed not only in the hypothalamus and pituitary gland, but also in peripheral tissues. Thus, in addition to modulating Growth hormone (GH) release, GHRH indirectly regulates cell proliferation in several other tissues, including tumor cells, through the GHRH / GH / IGF-1 axis. GHRH can also directly regulate cell growth through paracrine / endocrine mechanisms by binding to the GHRH receptor in target cells.
For this reason, synthetic GHRH agonists and antagonists have attracted much attention in recent years as global regulators of cell growth with therapeutic potential, including tissue regeneration and tumor suppression. GHRH has been shown to stimulate angiogenesis in human neuroendocrine tumors by promoting VEGF secretion. GHRH agonists applied to the postinfarction myocardium improved cardiac remodeling and helped resolve ischemia. GHRH antagonists are widely used to inhibit angiogenesis and tumor cell proliferation in prostate cancer, endometrial cancer, non-small cell lung cancer, and ovarian cancer.
How does GHRH work
The GHRH / Growth hormone / IGF-1 axis is the basic endocrine regulatory pathway that contributes to physical and metabolic homeostasis. GHRH is synthesized and stored in the hypothalamus and transported to the pituitary gland, where it activates signaling by binding to a specific receptor (GHRH-R) on the pituitary gland. Growth hormone is stimulated by GHRH and secreted by somatotropes in the front of the pituitary gland.
Growth hormone and IGF-1 effects
Circulating Growth hormone exerts its effect by directly binding to a number of cell types with Growth hormone receptors or by indirect interaction with IGF-1. IGF-1 is produced mainly in the liver and muscles and regulates cell proliferation, differentiation and maturation in several tissues, such as bone, cartilage, skeletal muscle, adipocytes and cardiomyocytes. Listening to the IGF-1 signaling pathway, GHRH-GH contributes to the basic physiology, metabolism and growth of the body, including skin, connective tissue and bone, wound healing, and blood homeostasis, including glucose and lipid control.
GHRH – Growth hormone – IGF-1 axis
Circulating growth growth hormone levels are regulated through long loop feedback and short loop feedback mechanisms of the GHRH / Growth hormone / IGF-1 axis. Because GHRH communicates through both the GHRH / GH / IGF-1 axis and through direct binding to GHRH-R on peripheral cells, there is huge therapeutic potential for both its agonists and antagonists to treat diseases that may be associated with any imbalance of Growth hormone.
GHRH effects and benefits
The main function of Growth hormone–releasing hormone (GHRH) is to stimulate growth hormone secretion by the pituitary gland. GHRH / growth hormone / IGF-1 axis mechanisms regulate cell proliferation, differentiation, and maturation in most tissues, such as bone, cartilage, skeletal muscle, adipocytes, and cardiomyocytes. Through the GH / IGF-1 signaling pathway, GHRH-GH contributes to basic physiology, metabolism and growth of the body, including glucose and lipid control. Most of the end results of GHRH activity are end results mediated by growth hormone activity:
- total regeneration, cell repair
- increased protein synthesis and muscle growth
- increased fat utilization by stimulating triglyceride degradation and adipocyte oxidation
- increased calcium retention and bone mineralization
- can help reduce the risk of cardiovascular disease
- supports brain function and health
GHRH possible side effects / in excess of growth hormone
- gigantism, acromegaly
- swelling of the hands and feet
- altered facial features
- enlarged organs
- high blood pressure and heart disease
- water retention
- low blood sugar
- reduced insulin sensitivity and the risk of diabetes
Optimal dose of GHRH (Growth hormone–releasing hormone) is often reported as 50-150 mcg of GHRH 3-5 times daily.
Administration of GHRH alone may not lead to a significant increase in growth hormone production, however, when GHRH is co-administered in combination with some growth hormone releasing peptides / GH secretagoues (for example such as Ipamorelin or GHRP-6, GHRP-2 and the like), there is a joint synergistic and significantly stronger effect that results in a significant increased pituitary growth hormone production.