Growth hormone receptor is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''GHR''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. GHR

orthologs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spec ...

have been identified in most

mammals A mammal () is a vertebrate animal of the class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three middle e ...

Structure

Growth hormone receptor (GHR) is a transmembrane protein consisting of 620 amino acids. The receptor is part of the

Type I cytokine receptor Type I cytokine receptors are transmembrane receptors expressed on the surface of cells that recognize and respond to cytokines with four α-helical strands. These receptors are also known under the name '' hemopoietin receptors'', and share a ...

family of receptors. GHR exists in two forms as a full length membrane-bound receptor and as a soluble GH binding protein (GHBP). GHR contains two fibronectin type III β domains in its extracellular domain, whereas the intracellular domain contains tyrosine Kinase JAK2 binding sites for SH2 proteins. JAK2 is the primary signal transducer for growth hormone.

Function

This gene encodes a protein that is a transmembrane receptor for

growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...

. Binding of growth hormone to the receptor leads to reorientation of a pre-assembled receptor dimer

dimerization In chemistry, dimerization is the process of joining two identical or similar molecular entities by bonds. The resulting bonds can be either strong or weak. Many symmetrical chemical species are described as dimers, even when the monomer is u ...

(the receptor may however also exist as monomers on the cell surface ) and the activation of an intra- and intercellular signal transduction pathway leading to growth. A common alternate allele of this gene, called GHRd3, lacks exon three and has been well characterized. Mutations in this gene have been associated with

Laron syndrome Laron syndrome (LS), also known as growth hormone insensitivity or growth hormone receptor deficiency (GHRD), is an autosomal recessive disorder characterized by a lack of insulin-like growth factor 1 (IGF-1; somatomedin-C) production in response ...

, also known as the growth hormone insensitivity syndrome (GHIS), a disorder characterized by short stature (proportional dwarfism). Other splice variants, including one encoding a soluble form of the protein (GHRtr), have been observed but have not been thoroughly characterized. Laron mice (that is mice genetically engineered to carry defective Ghr), have a dramatic reduction in body mass (only reaching 50% of the weight of normal siblings), and also show a ~40% increase in lifespan. Euryzygomatomyinae GHR AA

Interactions

Growth hormone receptor has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...

with

SGTA Small glutamine-rich tetratricopeptide repeat-containing protein alpha is a protein that in humans is encoded by the ''SGTA'' gene. ''SGTA'' orthologs have also been identified in several mammals for which complete genome data are available. STGA b ...

PTPN11 Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) also known as protein-tyrosine phosphatase 1D (PTP-1D), Src homology region 2 domain-containing phosphatase-2 (SHP-2), or protein-tyrosine phosphatase 2C (PTP-2C) is an enzyme that in hu ...

Janus kinase 2 Janus kinase 2 (commonly called JAK2) is a non-receptor tyrosine kinase. It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CS ...

Suppressor of cytokine signaling 1 Suppressor of cytokine signaling 1 is a protein that in humans is encoded by the ''SOCS1'' gene. ''SOCS1'' orthologs have been identified in several mammals for which complete genome data are available. Function This gene encodes a member of t ...

and CISH.

Evolution

The ''GHR'' gene is used in animals as a

nuclear DNA Nuclear DNA (nDNA), or nuclear deoxyribonucleic acid, is the DNA contained within each cell nucleus of a eukaryotic organism. It encodes for the majority of the genome in eukaryotes, with mitochondrial DNA and plastid DNA coding for the rest. ...

phylogenetic marker. The exon 10 has first been experienced to explore the phylogeny of the major groups of

Rodentia Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia ( ), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are na ...

. GHR has also proven useful at lower

taxonomic 280px, Generalized scheme of taxonomy Taxonomy is a practice and science concerned with classification or categorization. Typically, there are two parts to it: the development of an underlying scheme of classes (a taxonomy) and the allocation ...

levels, ''e.g.'', in octodontoid, arvicoline, muroid, murine, and peromyscine rodents, in arctoid and

felid Felidae ( ) is the Family (biology), family of mammals in the Order (biology), order Carnivora colloquially referred to as cats. A member of this family is also called a felid ( ). The 41 extant taxon, extant Felidae species exhibit the gre ...

carnivores, and in

dermoptera Colugos (), flying lemurs, or cobegos (), are arboreal gliding euarchontogliran mammals that are native to Southeast Asia. Their closest evolutionary relatives are primates. There are just two living species of colugos: the Sunda flying lemur ...

ns. Note that the GHR intron 9 has also been used to investigate the

mustelid The Mustelidae (; from Latin , weasel) are a diverse family of carnivoran mammals, including weasels, badgers, otters, polecats, martens, grisons, and wolverines. Otherwise known as mustelids (), they form the largest family in the suborde ...

and hyaenid

carnivores A carnivore , or meat-eater (Latin, ''caro'', genitive ''carnis'', meaning meat or "flesh" and ''vorare'' meaning "to devour"), is an animal or plant whose nutrition and energy requirements are met by consumption of animal tissues (mainly mu ...

phylogenetics.

Antagonists

Growth hormone

receptor antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of rec ...

s such as

pegvisomant Pegvisomant, sold under the brand name Somavert, is a growth hormone receptor antagonist used in the treatment of acromegaly. It is primarily used if the pituitary gland tumor causing the acromegaly cannot be controlled with surgery or radiation ...

(trade name ''Somavert'') are used in the treatment of

acromegaly Acromegaly is a disorder that results in excess growth of certain parts of the human body. It is caused by excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet. There ...

. They are used if the tumor of the

pituitary gland The pituitary gland or hypophysis is an endocrine gland in vertebrates. In humans, the pituitary gland is located at the base of the human brain, brain, protruding off the bottom of the hypothalamus. The pituitary gland and the hypothalamus contr ...

causing the acromegaly cannot be controlled with surgery or radiation, and the use of

somatostatin Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by #Nomenclature, several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G ...

analogues is unsuccessful. Pegvisomant is delivered as a powder that is mixed with water and injected under the skin.

References

External links

*
Illustration at nih.gov

Growth Hormone Receptor
: Molecule of the Month by Shuchismita Dutta and David Goodsell (April 2004)
PDBe-KB
provides an overview of all the structure information available in the PDB for Human Growth hormone receptor {{PDB_Gallery, geneid=2690