Mechanism of growth hormone action​

Mechanism of growth hormone action

Similar to other peptide hormones, growth hormone works by binding to its receptors.
However, binding of a growth hormone molecule to two receptor molecules leads to receptor dimerization. This dimerization will help you understand how GH works and can futher understand the various biological effects of GH.

l Growth hormone (GH)

Growth hormone, also known as helping growth hormone, is a pituitary specific protein hormone secreted by cells. It is transported to the target tissue by blood.
The growth hormone of many species have been sequenced. It is composed of 191 amino acids,molecular weight is 22kDa.There are two disulfide bonds, one linking cystine residues on 53 and 164 point . Another link to 181 and 189 point.these two disulfide bonds cause the molecule to form two rings.

There are two GHR binding sites 1 and 2 per GH,they are spatially separated from each other.Binding site 1 on the right side of the molecule ,which constitutes the surface of A~B and AB-Loop.Binding site 2 on the left constitutes the A and C surfaces. The amino acid of cow’s GH differs from sheep in only one position . So this explains why cow’s GH can play a biological role in sheep.However, the GH of other species is different to some extent.The GH sequence of cattle is 90% homologous to the GH sequence of pigs.Cow and pig’s GH sequence and human GH sequence has only 65% homology.This can explain Cow and Pig’s GH Why can’t it work on people.

2 Growth hormone receptor (GHR)

Growth hormone receptor (GHR) is a transmembrane glycoprotein,is a member of the cytokine/hematopoietic factor receptor superfamily. Approximately 620 amino acids, the exact number of amino acids in different species is slightly different. Most animals have GHR molecular weights ranging from 100 to 130 kDa. GHR is abundantly exist in liver and fat cells.However, it has been reported that lymphocytes, fibroblasts, macrophages, and chondrocytes ,B-insulin cells and osteoblasts also exist GHR .
GHR consists of three domains: the N-terminal 246 amino acid domain outside the plasma membrane;A 25 amino acid transmembrane domain in the middle;C-terminal 350 amino acid domain inside the plasma membrane,The C-terminal peptide on the inner side of the plasma membrane has a large number of tyrosine residues.Like other cytokines, the GHR cytoplasmic domain includes seven cysteines and five glycosylation sites;The cytoplasmic domain has two motifs: one is the proline-rich Box1 at the proximal end of the membrane; the other is the cytoplasmic motif for Box2. It starts with a hydrophilic amino acid and is a negatively charged amino acid in the middle. End with one or two positively charged amino acid residues.These areas of GHR play an important role in signal transduction.
All receptor superfamily members are present in BoX1,it is composed of 8 I-X-X-X-A1-P-X-P amino acids,within them , I, A1, X and P are represented seperately hydrophobic groups, fatty residues, respectively, other amino acids and proline. Mutation or deletion of BoX1, BoX2 will result in incorrect ligand regulation of cell growth. GHR belongs to class I cytokine receptor .Blood cytokine receptor family. The main components of class I receptors include: fibronectin L-type component, N-terminal four conserved cysteines, and a cytokine homology region (CHR). Cytokine homologous region Fixed, outer C-end of the membrane Try-Ser-X-Try-Ser (WSXWS) primitive. Moutoussamy et al. found that GHR does not have this WS motif. It is replaced by the amino acid Try-G1y-G1u-Phe-Ser, which plays a key role in receptor ligand binding.

3 GHR dimer

One molecule of GH combines with two molecules of GHR to cause receptor II.Polymerization is a key step in the biological function of GH. Both binding sites 1 and 2 of growth hormone can bind to the same region of GHR.The complexity of the sequence is that the GH receptor (GHR) is always binding GH site 1,then the second GHR is combined with site 2. The internal part of the receptor molecule is maintained by two such interactions,Polymer complexity.When adding GHR-expressing cells, mutated GH does not dimerize GHR,this will cause GH lose its biological function, which indicates that GHR dimerization is necessary for GH to function.This indicates that GHR dimerization is essential for GH .In addition, GH mutants that bind to site 2 can form a 1/1 Complex. At physiological hormone concentrations (0.1~1nm), GH is combined with GHR at 1/2.At super-radical hormone concentration (>1um), the hormone saturates all receptor molecules to form a 1/1 complex, which blocking receptor dimerization and information transfer.GHR dimerization causes information molecules or information channels to activate various biology of GH. The GH biological function is being done by through these informational molecules .


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