Parathyroid hormone-related protein

Source: Wikipedia, the free encyclopedia.

PTHLH
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
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 MbChr 6: 147.15 – 147.17 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Parathyroid hormone-related protein (PTHrP) is a

teeth, vascular tissues
and other tissues.

Function

PTHrP acts as an

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. PTHrP plays a major role in regulating calcium homeostasis in vertebrates, including sea bream, chick, and mammals.[5]

In 2005, Australian pathologist and researcher

bone formation.[6] Martin and Miao et al. demonstrated that osteoblast-specific ablation of PTHrP in mice results in osteoporosis and impaired bone formation both in vivo and ex vivo, which reiterates the phenotype of mice with haploinsufficiency of PTHrP. By these findings, they demonstrated that PTHrP plays a central role in physiological regulation of bone formation by promoting recruitment and survival of osteoblasts. It may also play a role in physiological regulation of bone resorption by enhancing osteoclast formation.[6]

Tooth eruption

PTHrP is critical in intraosseous phase of tooth eruption where it acts as a signalling molecule to stimulate local bone resorption.[7] 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.[8]

Mammary glands

Further information: Breast development and Mammary gland § Development

It aids in normal

calcium sensing receptors, as well as placental
transfer of calcium.

Humoral hypercalcemia of malignancy

PTHrP is related in function to parathyroid hormone(PTH). When a

paraneoplastic phenomenon
. PTHrP 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).[12] 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.[13]

However, PTHrP has a less sustained action than PTH on PTHR1 activation, which may explain at least in part its reduced ability to stimulate 1,25-dihydroxyvitamin D (1,25(OH)2 vitamin D) production and indirectly intestinal calcium absorption through an action to increase circulating levels of 1,25(OH)2 vitamin D.[14]

Growth Plate

PTHrP is found in the proliferative zone of the growth plate. It is one of the main proteins that regulates mesenchymal stem cell activity. Current research suggests that PTHrP promotes the proliferation of early-phase chondrocytes and inhibits their differentiation into hypertropic chondrocytes. It is involved in a negative feedback loop with Indian Hedgehog (Ihh). [15]

Genetics

Four

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.[16]

Discovery

The protein was first isolated in 1987 by Thomas J. Martin's team at the University of Melbourne.[17][18] 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.[19]

Interactions

Parathyroid hormone-related protein has been shown to interact with KPNB1[20][21] and Arrestin beta 1.[22]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000087494 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000048776 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. S2CID 54474550
    .
  6. ^
    PMID 16138187
    .
  7. PMID 18434571
    .
  8. PMID 9751753
    .
  9. S2CID 25109329
    .
  10. PMID 16168142
    .
  11. PMID 3043221
    .
  12. PMID 1658941
    .
  13. PMID 15673803
    .
  14. ISBN 978-0-12-341103-7
    . Retrieved October 12, 2022.
  15. ^ Kronenberg, H. M. “PTHrP and Skeletal Development.” Annals of the New York Academy of Sciences 1068, no. 1 (April 1, 2006): 1–13. https://doi.org/10.1196/annals.1346.002.
  16. ^ "Entrez Gene: PTHLH parathyroid hormone-like hormone".
  17. PMID 1935171
    .
  18. ^ US5460978A, Martin TJ, Moseley JM, Kemp BE, Wettenhall RE, "Protein active in humoral hypercalcemia of malignancy-PthrP", issued October 24, 1995 
  19. PMID 16138191
    .
  20. PMID 12504010
    .
  21. PMID 11401507
    .
  22. S2CID 83640616
    .

Further reading

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

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