Parathyroid hormone-related protein

PTHLH
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3H3G, 1BZG, 1M5N, 3FFD
Identifiers
Aliases	PTHLH, BDE2, HHM, PLP, PTHR, PTHRP, parathyroid hormone-like hormone, parathyroid hormone like hormone
External IDs	OMIM: 168470 MGI: 97800 HomoloGene: 2113 GeneCards: PTHLH
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12p11.22 Start 27,958,084 bp[1] End 27,972,733 bp[1]
RNA expression pattern Bgee Top expressed in periodontal fiber dorsolateral prefrontal cortex esophagus caudate nucleus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function peptide hormone receptor binding hormone activity GO:0001948 protein binding Cellular component extracellular region nucleus Golgi apparatus nucleoplasm extracellular space cytoplasm cytosol Biological process regulation of gene expression skeletal system development osteoblast development cell-cell signaling female pregnancy negative regulation of chondrocyte differentiation adenylate cyclase-activating G protein-coupled receptor signaling pathway cAMP metabolic process positive regulation of cell population proliferation negative regulation of cell population proliferation epidermis development regulation of signaling receptor activity G protein-coupled receptor signaling pathway bone mineralization negative regulation of chondrocyte development Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5744	19227
Ensembl	ENSG00000087494	ENSMUSG00000048776
UniProt	P12272	P22858
RefSeq (mRNA)	NM_002820 NM_198964 NM_198965 NM_198966	NM_008970
RefSeq (protein)	NP_002811 NP_945315 NP_945316 NP_945317	n/a
Location (UCSC)	Chr 12: 27.96 – 27.97 Mb	n/a
PubMed search	[2]	[3]
Wikidata
View/Edit Human View/Edit Mouse

Parathyroid hormone-related protein (or PTHrP) is a protein member of the parathyroid hormone family secreted by mesenchymal stem cells. It is occasionally secreted by cancer cells (breast cancer, certain types of lung cancer including squamous-cell lung carcinoma). However, it also has normal functions in bone, tooth, vascular and other tissues.

Function[]

PTHrP acts as an endocrine, autocrine, paracrine, and intracrine hormone. It regulates endochondral bone development by maintaining the endochondral growth plate at a constant width. It also regulates epithelial–mesenchymal interactions during the formation of the mammary glands.

Tooth eruption[]

PTHrP is critical in intraosseous phase of tooth eruption where it acts as a signalling molecule to stimulate local bone resorption. Without PTHrP, the bony crypt surrounding the tooth follicle will not resorb, and therefore the tooth will not erupt. In the context of tooth eruption, PTHrP is secreted by the cells of the reduced enamel epithelium.

Mammary glands[]

It aids in normal mammary gland development.^[4][5] It is necessary for maintenance of the mammary bud. Loss of PTHrP or its receptor causes the mammary bud cell fate to change back into epidermis. In lactation, it may regulate in conjunction with the calcium sensing receptor the mobilization and transfer of calcium to the milk, as well as placental transfer of calcium.

Humoral hypercalcemia of malignancy[]

PTHrP is related in function to the "normal" parathyroid hormone. When a tumor secretes PTHrP, this can lead to hypercalcemia.^[6] As this is sometimes the first sign of the malignancy, hypercalcemia caused by PTHrP is considered a paraneoplastic phenomenon. PTHR1 is responsible for most cases of humoral hypercalcemia of malignancy.

PTHrP shares the same N-terminal end as parathyroid hormone and therefore it can bind to the same receptor, the Type I PTH receptor (PTHR1). PTHrP can simulate most of the actions of PTH including increases in bone resorption and distal tubular calcium reabsorption, and inhibition of proximal tubular phosphate transport. PTHrP lacks the normal feedback inhibition as PTH. ^[7]

However, PTHrP is less likely than PTH to stimulate 1,25-dihydroxyvitamin D production. Therefore, PTHrP does not increase intestinal calcium absorption.

Genetics[]

Four alternatively spliced transcript variants encoding two distinct isoforms have been observed. There is also evidence for alternative translation initiation from non-AUG (CUG and GUG) start sites, in-frame and downstream of the initiator AUG codon, to give rise to nuclear forms of this hormone.^[8]

Discovery[]

The protein was first isolated in 1987 by T. J. Martin's team at the University of Melbourne. Miao et al. showed that disruption of the PTHrP gene in mice caused a lethal phenotype and distinct bone abnormalities, suggesting that PTHrP has a physiological function.

Interactions[]

Parathyroid hormone-related protein has been shown to interact with KPNB1^[9][10] and Arrestin beta 1.^[11]

See also[]

• Analogs used as pharmaceutical drugs
  • Teriparatide
  • Abaloparatide

References[]

Further reading[]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.