GHBP, GH receptor.
Growth hormone receptor (GHR) belongs to the cytokine receptor family. GHR binds two receptor molecules, leading to signal transduction via receptor dimerization. At elevated concentrations, growth hormone (GH) exhibits antagonist properties due to significant differences in binding affinities at the respective sites. This antagonistic effect can be further enhanced by reducing binding at the low-affinity site.
GHBP, GH receptor.
Growth Hormone Binding Protein (GHBP) is a crucial component in the regulation of growth hormone (GH) activity. GHBP is derived from the extracellular domain of the Growth Hormone Receptor (GHR) and exists in the bloodstream, where it binds to GH, modulating its availability and activity. The recombinant form of GHBP, specifically from rats, has been extensively studied to understand its role in GH physiology and its potential therapeutic applications.
GHBP is a soluble protein that binds to GH with high affinity, similar to the membrane-bound GHR. The binding of GH to GHBP can prolong the half-life of GH in the bloodstream, thereby enhancing its biological activity. This interaction is crucial for maintaining the appropriate levels of GH in the body and ensuring its proper physiological functions.
Recombinant GHBP can be produced using various expression systems, including bacterial, yeast, and mammalian cells. The most common method involves the use of Escherichia coli (E. coli) due to its simplicity and cost-effectiveness. The gene encoding GHBP is cloned into an expression vector, which is then introduced into E. coli cells. The bacteria are cultured, and the recombinant protein is expressed, harvested, and purified using techniques such as affinity chromatography.
Studies have shown that recombinant GHBP can enhance the growth-promoting activity of GH in rats. For instance, coadministration of recombinant human GHBP (rhGHBP) with recombinant human GH (rhGH) in hypophysectomized rats or GH-deficient dwarf rats resulted in increased body weight gain and bone growth . This effect is attributed to the ability of GHBP to slow the clearance of GH from the bloodstream, thereby increasing its bioactivity.
The localization and regulation of GHBP in the rat growth plate have been investigated using immunohistochemical methods. GHBP is found in various layers of the growth plate, including germinal and proliferative chondrocytes, as well as early maturing chondrocytes . The expression of GHBP is regulated by hormonal factors, such as thyroid hormones and glucocorticoids, which can influence its levels and activity in the growth plate.
The ability of GHBP to modulate GH activity has significant therapeutic implications. By enhancing the bioactivity of GH, recombinant GHBP could potentially be used to treat conditions associated with GH deficiency, such as dwarfism and growth retardation. Additionally, understanding the role of GHBP in GH physiology could lead to the development of novel therapeutic strategies for managing GH-related disorders.