PTH receptor-1 signalling—mechanistic insights and therapeutic prospects

Cheloha, Ross W.; Gellman, Samuel H.; Vilardaga, Jean-Pierre; Gardella, Thomas J.

doi:10.1038/nrendo.2015.139

Cited by 209 publications

(172 citation statements)

References 124 publications

Supporting

Mentioning

168

Contrasting

Unclassified

Order By: Relevance

“…Upon ligand binding (PTH or PTHrP is mentioned in the figure), the receptor (PTH1R) activates the G protein. Then, the Gsa subunit triggers the activation of the adenylate cyclase leading to PTHrP promotes endochondral ossification, by binding to PTH1R (7).…”

Section: Figurementioning

confidence: 99%

From pseudohypoparathyroidism to inactivating PTH/PTHrP signalling disorder (iPPSD), a novel classification proposed by the EuroPHP network

Thiele

Mantovani

Barlier

et al. 2016

European Journal of Endocrinology

132

124

View full text Add to dashboard Cite

Objective: Disorders caused by impairments in the parathyroid hormone (PTH) signalling pathway are historically classified under the term pseudohypoparathyroidism (PHP), which encompasses rare, related and highly heterogeneous diseases with demonstrated (epi)genetic causes. The actual classification is based on the presence or absence of specific clinical and biochemical signs together with an in vivo response to exogenous PTH and the results of an in vitro assay to measure Gsa protein activity. However, this classification disregards other related diseases such as acrodysostosis (ACRDYS) or progressive osseous heteroplasia (POH), as well as recent findings of clinical and genetic/epigenetic background of the different subtypes. Therefore, the EuroPHP network decided to develop a new classification that encompasses all disorders with impairments in PTH and/or PTHrP cAMP-mediated pathway. Design and methods: Extensive review of the literature was performed. Several meetings were organised to discuss about a new, more effective and accurate way to describe disorders caused by abnormalities of the PTH/PTHrP signalling pathway. Results and conclusions: After determining the major and minor criteria to be considered for the diagnosis of these disorders, we proposed to group them under the term 'inactivating PTH/PTHrP signalling disorder' (iPPSD). This terminology: (i) defines the common mechanism responsible for all diseases; (ii) does not require a confirmed genetic defect; (iii) avoids ambiguous terms like 'pseudo' and (iv) eliminates the clinical or molecular overlap

show abstract

Section: Figurementioning

confidence: 99%

From pseudohypoparathyroidism to inactivating PTH/PTHrP signalling disorder (iPPSD), a novel classification proposed by the EuroPHP network

Thiele

Mantovani

Barlier

et al. 2016

European Journal of Endocrinology

132

124

View full text Add to dashboard Cite

show abstract

“…Female were twice more affected by PHP than men [39]. In PHP I subtypes the exogenous PTH fails to increase serum calcium level or increase the urinary phosphate and cAMP secretion, due to impairment in PTH receptor coupling [26,38]. But, in PHP type II the same test as above fails to increase serum calcium level or increase the urinary phosphate secretion whereas the cAMP urinary secretion is normal, these means the defect is distal to cAMP generation point [37,40].…”

Section: Gene Rolementioning

confidence: 99%

“…An alteration of the gene coding for Gsa (GNAS) locus causes PHP Ia and PHP Ib [26]. GNAS location is on the long arm of chromosome 20 (20q13.3); the very structurally similar murine homolog is on chromosome 2 [27].…”

Section: Gene Rolementioning

confidence: 99%

Calcification of Soft Tissues in a Family, Case Report and Review of Pseudohypoparathyroidism

Navaeifar¹,

Zamanfar²

2017

J Rare Disord Diagn Ther

View full text Add to dashboard Cite

Pseudohypoparathyroidism and pseudo-pseudohypoparathyroidism are rare genetic disorders of calcium metabolism and resistance to the action of Parathormone. Although the genetic details of these conditions are not fully diagnosed, role of gene coding for stimulatory G protein locus was studied and imprinting in its inheritance was proved. We report three cases of a family member with calcification in soft tissues that show Pseudohypoparathyroidism in father and his sister and pseudo-pseudohypoparathyroidism in his son. history of two times seizure in the past years. The patient's paternal aunt had similar objective finding similar to patient's father but she didn't agree to involve in our assessment. The parents was non-consanguineous and the mother had not the same problems and was normal in physical examination and anthropometric evaluation. The other 3.5 year old boy of this parent had not objective specific finding. In evaluation of 33 year old father, low total calcium level (6.9 mg/dL), high phosphorus (5.5 mg/dL), normal Alkaline phosphatase (277 U/L), very high PTH (650 pg/ml), normal kidney and thyroid function tests were found. The 25-OH-Vit D was in mid-normal range and ultrasound evaluation of kidneys do not demonstrate significant pathology. The brain CT scan showed calcification of basal ganglia and cerebellum nuclei (Figure 2). KeywordsAccording to clinical and para-clinical findings, such as hypocalcemia, hyperphosphatemia, elevated PTH, shortening of metacarpus, facial sign and subcutaneous calcification, the father's disease is a classic form of PHP type I (a or c) with AHO features but without obvious other evaluated hormone resistance. Differential diagnosis for subcutaneous ossification in our target child were: dystrophic soft tissue calcification, causing chondro-calcinosis, Fibrodysplasia ossificans progressive, posttraumatic osteoma cutis, metastatic calcification, idiopathic tumoural calcinosis, scleroderma, dermatomyositis, cysticercosis, myositis ossificans and soft tissue sarcoma. These wide range of differential diagnosis from trauma to malignancy were simply narrowed when his father's observed after a simple family history taking! Multiple subcutaneous calcifications in a child when his father shows a classic form of PHP, strike PPHP in the mind because of its genetic nature. As we discuss it in the next section, in a family with history of PHP when the father is the origin of gene, its imprinting led to PPHP in child. When a child has PPHP, and the father shows PHP features, the father's type of PHP is Ia. In the absence of genetic study and evaluation of urine cAMP after synthetic PTH administration it is difficult to say our diagnosis is definite. According to European PHP network classification for PHP the father case has two major criteria and is a case of "inactivating PTH/PTHrP signaling disorder" (iPPSD) without genetic study. PathophysiologyBecause of critical function of calcium ion in much vital enzymatic process and electrical activity of neuron, muscle conducti...

show abstract

“…PTHrP antagonists have been studied also in enchondroma's, patients with Olliers syndrome, chondroblastoma's and chondrosarcoma's. Research with structurally modified PTH1R ligands has revealed deeper insights in the function of the receptor but didn't result in clinical applications yet [102].…”

Section: Pthrp/pth1r Antogonists and Agonistsmentioning

confidence: 99%

Untitled

2017

EMIJ

View full text Add to dashboard Cite

In this mini-review the role of parathyroid hormone-related peptide (PTHrP) in physiology and pathophysiology is discussed. Evolving from an unknown humoral factor in the HHM (Hypercalcemia of malignancy) syndrome its role as a "masterregulator" in the PTH family following identification is reviewed. PTHrP has more paracrine and autocrine functions in virtually all tissues than classical endocrine functions and is essential in embryonic, fetal and post-natal life. The physiological functions are near endless. The development of PTH/PTHrP receptor antagonist and agonists has been difficult and disappointing. Its role as a possible cytokine itself and as a regulatory thermogenesis factor in brown adipose tissue in cancer cachexia is discussed. PTHrP assays must be improved for PTHrP to be a reliable biomarker in oncology and to resolve the function of local proteolytic PTHrP fragments which are largely a mystery until now.

show abstract

PTH receptor-1 signalling—mechanistic insights and therapeutic prospects

Cited by 209 publications

References 124 publications

From pseudohypoparathyroidism to inactivating PTH/PTHrP signalling disorder (iPPSD), a novel classification proposed by the EuroPHP network

From pseudohypoparathyroidism to inactivating PTH/PTHrP signalling disorder (iPPSD), a novel classification proposed by the EuroPHP network

Calcification of Soft Tissues in a Family, Case Report and Review of Pseudohypoparathyroidism

Untitled

Contact Info

Product

Resources

About