A G Protein-Linked Receptor for Parathyroid Hormone and Parathyroid Hormone-Related Peptide

Jüppner, Harald; Abou‐Samra, Abdul Badi; Freeman, Mason W.; Kong, Xiangfu; Schipani, Ernestina; Richards, Jennifer C.; Kolakowski, Lee F.; Hock, Janet M.; Potts, John T.; Kronenberg, Henry M.; Segre, Gino V.

doi:10.1126/science.1658941

Cited by 1,178 publications

(639 citation statements)

References 27 publications

Supporting

Mentioning

612

Contrasting

Unclassified

Order By: Relevance

“…PTHrP and parathyroid hormone (PTH), the main hypercalcemic hor mone in vertebrates, evolved from a common, ancestral gene. Within a species, the two proteins share a high, about 70% N-terminal amino acid (aa) homology and bind with similar affinity to a shared PTH/PTHrP receptor (Jüppner et al, 1991). PTH is secreted from the parathyroid glands; however, pthrp is expressed in and PTHrP secreted by a variety of tissues, including many epithelia (de Papp and Stewart, 1993).…”

Section: Pthrp Its Discoverymentioning

confidence: 99%

Parathyroid hormone-related protein in teleost fish

Abbink

Flik

2007

General and Comparative Endocrinology

View full text Add to dashboard Cite

A brief description is given of the discovery of PTHrP and the roles of the peptide in mammalian physiology. Next, the occurrence of PTHrP in the earliest vertebrates, sharks, skates and fishes, is reviewed and the calciotropic functions of PTHrP are addressed more spe cifically in fishes. Parathyroid hormone-related protein (PTHrP) is a hypercalcemic hormone in teleostean fishes, but also has para-and autocrine functions. After the isolation and identification of fish PTHrP and PTHrP receptors and the subsequent development of recom binant protein and a real-time quantitative PCR, a calciotropic role of PTHrP in fish physiology could be assessed. PTHrP influences calcium physiology via regulation of calcium mobilisation from internal sources (bone and scales) and via calcium uptake from the envi ronment (water and diet). Continuous variations in the need for calcium and in the availability of environmental calcium require fast calciotropes to guarantee calcium balance, in which PTHrP is pivotal for the fish. PTHrP is essential in fish bone physiology, e.g. in min eralisation and calcium reabsorption from the scales. Moreover, PTHrP plays a role in vitellogenesis, cortisol production, regulation of renal Mrp2 activity and melatonin synthesis. The plethora of functions of PTHrP in fish concern endocrine, paracrine and autocrine (and possibly intracrine) functions; calciotropic actions of PTHrP at the organismal and cellular level are prominent in fish. The strong con servation of the pthrp gene in the vertebrate lineage and the N-terminal similarity of the coded proteins relates to the important role of PTHrP in calcium physiology that is of paramount importance to all physiological processes. Recent and ongoing studies will contribute to our rapidly expanding knowledge of the original physiological functions of PTHrP in teleost fish.

show abstract

Section: Pthrp Its Discoverymentioning

confidence: 99%

Parathyroid hormone-related protein in teleost fish

Abbink

Flik

2007

General and Comparative Endocrinology

View full text Add to dashboard Cite

show abstract

“…(9) The PTH receptor on target cells is activated by the binding of PTH or PTHrP. (10) In addition, PTH upregulates RANKL gene expression and protein production on osteoblasts and stromal cells and therefore can activate osteoclasts precursors to develop into mature resorbing osteoclasts. (11) Interestingly, the in vivo effect of PTH depends on the dose and frequency of administration.…”

Section: Introductionmentioning

confidence: 99%

Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow

Jacome-Galarza

Lee

Lorenzo

et al. 2010

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Parathyroid hormone (PTH) increases both the number of osteoclast in bone and the number of early hematopoietic stem cells (HSCs) in bone marrow. We previously characterized the phenotype of multiple populations of bone marrow cells with in vitro osteoclastogenic potential in mice. Here we examined whether intermittent administration of PTH influences these osteoclast progenitor (OCP) populations. C57BL/6 mice were treated with daily injections of bPTH(1-34) (80 mg/kg/day) for 7 or 14 days. We found that PTH caused a significant increase in the percentage of TN/CD115 þ CD117 high and TN/CD115 þ CD117 int cells ( p < .05) in bone marrow on day 7. In contrast, PTH decreased the absolute number of TN/CD115 þ CD117 low cells by 39% on day 7 ( p < .05). On day 14, there was no effect of PTH on osteoclast progenitor distribution in vivo. However, PTH treatment for 7 and 14 days did increase receptor activator of NF-kB ligand (RANKL)-and macrophage colony-stimulating factor (M-CSF)-stimulated in vitro osteoclastogenesis and bone resorption in TN/ CD115 þ cells. In the periphery, 14 days of treatment increased the percentage and absolute numbers of HSCs (Lin À CD117 þ Sca-1 þ ) in the spleen ( p < .05). These data correlated with an increase in the percent and absolute numbers of HSCs in bone marrow on day 14 ( p < .05). Interestingly, the effects on hematopoietic progenitors do not depend on osteoclast resorption activity. These results suggest that in vivo PTH treatment increased in vitro osteoclastogenesis and resorption without altering the number of osteoclast precursors. This implies that in vivo PTH induces sustained changes, possibly through an epigenetic mechanism, in the in vitro responsiveness of the cells to M-CSF and RANKL. ß

show abstract

“…What remains from this heritage is a similar structural organization of the two genes and a stretch of homologous sequence at the N-terminus of each mature gene product. These N-terminal products appear to be served by a common receptor (the type 1 PTH/PTHrP receptor, PTH1R), although they function in two quite separate domains, PTH as a classical systemic peptide hormone and PTHrP as predominately an autocrine/paracrine regulatory molecule [1][2][3][4][5]. The segregation and specificity of PTH and PTHrP signaling in these two domains are more or less complete, and this is attributed to the lability and sequestration of PTHrP in its microenvironments as well as variations in PTH1R density in PTH and PTHrP targets [1,2,[5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Mechanical regulation of PTHrP expression in entheses

Chen¹,

Macica²,

Nasiri³

et al. 2007

Bone

View full text Add to dashboard Cite

The PTHrP gene is expressed in the periosteum and in tendon and ligament insertion sites in a PTHrPlacZ knockin reporter mouse. Here, we present a more detailed histological evaluation of PTHrP expression in these sites and study the effects of mechanical force on PTHrP expression in selected sites. We studied the periosteum and selected entheses by histological, histochemical, and in situ hybridization histochemical techniques, and tendons or ligaments were unloaded by tail suspension or surgical transection. In the periosteum, PTHrP is expressed in the fibrous layer and the type 1 PTH/PTHrP receptor (PTH1R) in the subjacent cambial layer. PTHrP has distinct temporospatial patterns of expression in the periosteum, one hot spot being the metaphyseal periosteum in growing animals. PTHrP is also strongly expressed in a number of fibrous insertion sites. In the tibia these include the insertions of the medial collateral ligament (MCL) and the semimembraneosus (SM). In young animals, the MCL and SM sites display a combination of underlying osteoblastic and osteoclastic activities that may be associated with the migration of these entheses during linear growth. Unloading the MCL and SM by tail suspension or surgical transection leads to a marked decrease in PTHrP/lacZ expression and a rapid disappearance of the subjacent osteoblastic population. We have not been able to identify PTHrP-lacZ in any internal bone cell population in the PTHrP-lacZ knockin mouse in either a CD-1 or C57Bl/6 genetic background.In conclusion, we have identified PTHrP expression in surface structures that connect skeletal elements to each other and to surrounding muscle but not in intrinsic internal bone cell populations. In these surface sites, mechanical force seems to be an important regulator of PTHrP expression. In selected sites and/or at specific times, PTHrP may influence the recruitment and/or activities of underlying bone cell populations.

show abstract

A G Protein-Linked Receptor for Parathyroid Hormone and Parathyroid Hormone-Related Peptide

Cited by 1,178 publications

References 27 publications

Parathyroid hormone-related protein in teleost fish

Parathyroid hormone-related protein in teleost fish

Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow

Mechanical regulation of PTHrP expression in entheses

Contact Info

Product

Resources

About