Parathyroid hormone-like protein is a secretory product of atrial myocytes.

Deftos, Leonard J.; Burton, Douglas W.; Brandt, David

doi:10.1172/jci116643

Cited by 76 publications

(38 citation statements)

References 46 publications

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“…Comparing the obtained results with the literature data [14,19,20] it was assumed that PTH and PTHrP have compensatory-modulating significance in order to preserve cardiac function. A number of studies [5,7,21] indicate involvement of the major calcium-regulating factor, PTH in the regulation of heart contractile activity.…”

Section: Introductionsupporting

confidence: 52%

Dose-dependent effect of parathyroid hormone 1-34 fragment and its influence mechanism on the functional activity of isolated heart

Ter-Markosyan¹,

Harutunyan²,

Sargsyan³

et al. 2012

OJMIP

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The present investigation is the continuation of our prior clinical studies on the content of parathyroid hormone (PTH), its paracrine analog, parathyroid hormone-related protein (PTHrP) and electrolytes in blood of patients with heart failure. The results of these studies formed the basis for the nomination of the hypothesis on PTH and PTHrP compensatorymodulating effect on the contractile activity of heart. The objective of this study is to elucidate the mechanism of the compensatory-modulating effect of PTH on heart functional activity, which is realized by the study of effective doses of PTH by pharmacological analysis, using different inhibitors. The dose-dependent effect of PTH on the heart contraction rate and amplitude is studied on the frog isolated heart by the method of non-invasive registration of heart contractile activity. The method is based on the photoelectric principle of the reflected from the contractile object light ray transformation into an electric signaling. It is shown that the most effective dose that has positive chronotropic and inotropic effects on heart is 10 -10 M hormone. To clarify the mechanism of PTH physiological dose action on the contractile activity of heart PTH 1-34 is combined with Ca-channel as well as phosphodiesterase blockers. The mentioned substances are applied based on the fact that PTH effect on target cells is mediated by secondary messengers, particularly calcium ions and cAMP. Based on the data obtained by combination of hormone with Verapamil (10 -5 M) and Theophylline (10 -4 M), we concluded on the involvement of calcium ions in the realization of chronotropic and cAMP in the inotropic effects on the heart.

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Section: Introductionsupporting

confidence: 52%

Dose-dependent effect of parathyroid hormone 1-34 fragment and its influence mechanism on the functional activity of isolated heart

Ter-Markosyan¹,

Harutunyan²,

Sargsyan³

et al. 2012

OJMIP

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“…PTHrP was stained with an immunohistochemical technique as described previously (22,23). Antigen retrieval techniques were not employed.…”

mentioning

confidence: 99%

“…Antigen retrieval techniques were not employed. The mouse monoclonal primary antibody directed against PTHrP 109-141, 9H7 (22,23), was used at a concentration of 10 Ag/mL for 1 hour at room temperature. Immunoreactivity was developed with a standard avidin-biotin complex alkaline phosphatase using Vector Red (kit SK-5100, Vector Laboratories, Burlingame, CA) as the chromogen and a 0.125% methyl green counterstain.…”

mentioning

confidence: 99%

Sex-Specific Survival Advantage with Parathyroid Hormone–Related Protein in Non–Small Cell Lung Carcinoma Patients

Hastings¹,

Laux²,

Casillas³

et al. 2006

Clinical Cancer Research

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Purpose: Parathyroid hormone^related protein (PTHrP) is commonly expressed in non^small cell lung carcinomas (NSCLC). Expression of the protein could have implications for progression of the disease because it regulates cancer cell growth, apoptosis, and angiogenesis. However, its relationship with survival has not been evaluated in a large-scale investigation. Experimental Design: PTHrP expression was assessed in paraffin-embedded tumor samples from 407 patients with NSCLC by immunohistochemistry. A pathologist unaware of the clinical history classified specimens as PTHrP positive or PTHrP negative. The log-rank test was used to compare survivals of PTHrP-positive and PTHrP-negative groups, and Cox regression was used to adjust for additional covariates.Results: Median survival was 55 versus 22 months (P < 0.001) in female patients with and without tumor PTHrP, respectively. Male survival was 38 months independent of PTHrP status. Stage, histology, age, and smoking history were also associated with increased longevity. PTHrP remained a significant predictor of survival for female patients after controlling for stage, histology, and age. Conclusions: In this study, PTHrP expression was associated with a survival advantage in female patients. Additional investigations must be done to ascertain whether the result is reproducible and independent of potential confounding covariates. Sex-dependent effects of PTHrP in lung cancer would open new avenues of research into the role of sex in cancer progression.Parathyroid hormone-related protein (PTHrP) was discovered as the factor responsible for hypercalcemia of malignancy. As the name implies, PTHrP shares structural similarities with PTH, specifically in the NH 2 -terminal 34 amino acids. Consequently, PTHrP 1-34 binds to the same receptor as PTH 1-34, the type 1 PTH/PTHrP receptor (PTH1R), and duplicates the effects of PTH 1-34 in tissues that bear the receptor, including causing hypercalcemia. Hypercalcemic effects are mediated through decreases in calcium excretion in kidney and increases in calcium release from bone. It is less widely appreciated that PTHrP also exerts effects direct effects on cancer cells that could be important in the pathology of malignancy.

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“…These results suggest that a single molecule may have opposite effects under physiological and pathological conditions [69]. PTHrP has been found in cardiomyocytes and co-localizes with atrial natriuretic peptide in granules within the atrial cells in the rat heart [70]. In PTH1R deficient mice widespread cardiomyocyte death occurred in midgestation.…”

Section: Pthrp In Smooth Muscle and The Cardiovascular Systemmentioning

confidence: 99%

Untitled

2017

EMIJ

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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.

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Parathyroid hormone-like protein is a secretory product of atrial myocytes.

Cited by 76 publications

References 46 publications

Dose-dependent effect of parathyroid hormone 1-34 fragment and its influence mechanism on the functional activity of isolated heart

Dose-dependent effect of parathyroid hormone 1-34 fragment and its influence mechanism on the functional activity of isolated heart

Sex-Specific Survival Advantage with Parathyroid Hormone–Related Protein in Non–Small Cell Lung Carcinoma Patients

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