SEARCH · Search PubMed

Results for “parathyroid hormone”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources

PubMed1995

Arg21 is the preferred kexin cleavage site in parathyroid-hormone-related protein.

Parathyroid-hormone-related protein (PTHrP) contains several potential sites for proteolytic processing. Although there is considerable evidence for the existence of cleaved products in vivo, little is known about the post-translational processing of PTHrP. We have used purified kexin (Kex2) protease to identify which cleavage sites in recombinant PTHrP(1-141) might be of physiological significance. Cleavage products were identified by N-terminal sequencing. Kex2 preferentially cleaved PTHrP(1-141) carboxy to the triplet arginine site Arg-Arg-Arg21 with a Km of 3.3 +/- 1.7 microM and a kcat of 6 +/- 1.2 s-1. Substitution of alanine for Arg19 resulted in substantially reduced conversion, while no detectable cleavage occurred when alanine was substituted for either Arg20 or Arg21. In contrast, the degree of Kex2 cleavage at Arg21 in PTHrP(1-34) was lower. No detectable cleavage occurred in an unrelated synthetic peptide containing both double and triple arginine sites. Low levels of cleavage also took place carboxy to Lys-Arg97, Lys-Arg105, Arg-Arg106 and Thr-Arg108. Cleavage carboxy to Lys-Arg105, the best of these minor sites, occurred with a Km of 8.4 +/- 2.7 microM and a kcat of 0.8 +/- 0.2 s-1. These studies indicate that the preferred Kex2 cleavage site in PTHrP(1-141) is carboxy to Arg-Arg-Arg21, which effectively destroys its parathyroid-hormone-like biological activity. Cleavage of this site by Kex2-related mammalian convertases in vivo may be an important mechanism for full elaboration of the non-parathyroid-hormone-like paracrine actions of PTHrP in a tissue-specific manner.

Arginine↗

PubMed1994

New aspects in the control of parathyroid hormone secretion.

Ca2+ binds to a parathyroid cell Ca2+ receptor, which is G protein-coupled and activates inositol triphosphate production. Mutations in the Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Chronic hypocalcemia increases parathyroid hormone messenger RNA levels and parathyroid cell hyperplasia. Parathyroid cells in vitro are heterologous in their response to Ca2+. The concept of a higher Ca2+ set-point in secondary hyperparathyroidism is controversial. Calcitriol is more effective than the less hypercalcemia analogues in decreasing parathyroid hormone messenger RNA and immunoreactive parathyroid hormone levels, and its kinetics are well established. Phosphate and estrogens regulate the parathyroid independently of 1,25 dihydroxyvitamin D3 and Ca2+. The physiology of the effects of endothelin and insulin-like growth factors on the parathyroid need to be established. Important advances are being made in understanding the regulation of parathyroid hormone synthesis and secretion, which are relevant to both normal physiology and the pathogenesis and treatment of diseases such as the secondary hyperparathyroidism of renal failure and osteoporosis.

Animals↗

PubMed1992

Intraoperative parathyroid hormone estimation: a valuable adjunct to parathyroid surgery.

Serial measurements of serum intact parathyroid hormone (PTH) and adjusted total calcium levels were performed on 10 patients during unilateral neck exploration for a solitary parathyroid adenoma localised preoperatively by ultrasound scan. Frozen section was performed peroperatively to establish the presence of parathyroid tissue. Levels of PTH were shown to be within the normal range within 15 min of adenoma removal (a mean of 13.4% of their preoperative values), allowing clear early distinction from unsuccessful surgery where no change occurred. Frozen section wrongly identified thyroid tissue as parathyroid in one case leading to a failure of the initial neck exploration. Our findings show that intraoperative PTH measurements can accurately predict whether all hyperfunctioning parathyroid tissue has been removed. This is not always possible using frozen section techniques. The wider use of intraoperative PTH measurement, particularly in difficult cases, may avoid the need for prolonged explorations to identify all four glands and, perhaps, biopsy of normal glands, replacing the current standard use of frozen section as a more reliable indicator of the success of parathyroid surgery.

Adenoma↗

PubMed1991

Intraoperative fall in plasma levels of intact parathyroid hormone after removal of one enlarged parathyroid gland in hyperparathyroid patients.

Plasma levels of intact parathyroid hormone (PTH) were measured intraoperatively before and after removal of one enlarged gland in 20 hyperparathyroid patients. In 13 patients with a single parathyroid adenoma, plasma levels of intact PTH-(1-84) had declined at 15 min after removal of the adenoma by 86.5 +/- 4.4% of baseline in the antecubital vein and by 85.6 +/- 4.2% in the ipsilateral internal jugular vein. In seven patients with parathyroid hyperplasia, the corresponding figures for decline at 15 min after removal of one enlarged parathyroid gland were only 26.6 +/- 6.4% and 7.8 +/- 29.4%. The fall in PTH levels was significantly less in hyperplasia than in adenoma (p less than 0.001). Thus 15 min after removal of one enlarged parathyroid gland, the decline in plasma level of intact PTH may distinguish between single adenoma and multiglandular disease as the cause of hyperparathyroidism.

Adenoma↗

PubMed1980

Adult-onset vitamin D-resistant osteomalacia with the unresponsiveness to parathyroid hormone.

Serum immunoreactive parathyroid hormone (PTH) levels were increased in a 50-yr-old man with a unique variant of adult-onset vitamin D-resistant osteomalacia, presenting with high phosphate clearance, mild hypocalcemia, and blunted hypercalcemic and phosphaturic responses to exogenous parathyroid extract. After normalization of his serum calcium level with a large amount of 1 alpha-hydroxycholecalciferol, a synthetic vitamin D analog, serum PTH levels and phosphate clearance returned to normal, and hypercalcemia as well as phosphaturia appeared when parathyroid extract was administered. Further studies demonstrated that the renal response could be restored by the administration of calcium with the suppression of PTH. The evidence presented suggests that the resistance of PTH in this patient was due to secondary hyperparathyroidism rather than to a defect of PTH-sensitive receptors of the kidney and bone or to inadequacy of vitamin D per se.

Calcium↗

PubMed2003

Usefulness of a rapid immunometric assay for intraoperative parathyroid hormone measurements.

Intraoperative parathyroid hormone (IO-PTH) measurements have been proposed to improve operative success rates in primary, secondary and tertiary hyperparathyroidism (PHP, SHP and THP). Thirty-one patients requiring parathyroidectomy were evaluated retrospectively from June 2000 to January 2002. Sixteen had PHP, 7 SHP and 8 THP. Serum samples were taken at times 0 (before resection), 10, 20 and 30 min after resection of each abnormal parathyroid gland. Samples from 28 patients were frozen at -70 C for subsequent tests, whereas samples from three patients were tested while surgery was being performed. IO-PTH was measured using the Elecsys immunochemiluminometric assay (Roche, Mannheim, Germany). The time necessary to perform the assay was 9 min. All samples had a second measurement taken by a conventional immunofluorimetric method. We considered as cured patients who presented normocalcemia in PHP and THP, and normal levels of PTH in SHP one month after surgery and who remained in this condition throughout the follow-up of 1 to 20 months. When rapid PTH assay was compared with a routine immunofluorimetric assay, excellent correlation was observed (r = 0.959, P < 0.0001). IO-PTH measurement showed a rapid average decline of 78.8% in PTH 10 min after adenoma resection in PHP and all patients were cured. SHP patients had an average IO-PTH decrease of 89% 30 min after total parathyroidectomy and cure was observed in 85.7%. THP showed an average IO-PTH decrease of 91.9%, and cure was obtained in 87.5% of patients. IO-PTH can be a useful tool that might improve the rate of successful treatment of PHP, SHP and THP.

Humans↗

PubMed2004

Nmp4/CIZ regulation of matrix metalloproteinase 13 (MMP-13) response to parathyroid hormone in osteoblasts.

Parathyroid hormone (PTH) regulation of matrix metalloproteinase-13 (MMP-13) expression in osteoblasts contributes to normal bone turnover. The PTH response region of the rat MMP-13 gene spans nucleotides (nt) -148 to -38 and supports binding of numerous transcription factors, including Runx2, necessary for osteoblast differentiation, c-Fos/c-Jun, and Ets-1. These trans-acting proteins mediate hormone induction via incompletely defined combinatorial interactions. Within this region, adjacent to the distal Runx2 site, is a homopolymeric(dA:dT) element (-119/-110 nt) that conforms to the consensus site for the novel transcription factor nuclear matrix protein-4/cas interacting zinc finger protein (Nmp4/CIZ). This protein regulates bone cell expression of type I collagen and suppresses BMP2-enhanced osteoblast differentiation. The aim of this study was to determine whether Nmp4/CIZ contributes to MMP-13 basal transcription and PTH responsiveness in osteoblasts. Electrophoretic mobility shift analysis confirms Nmp4/CIZ binding within the MMP-13 PTH response region. Mutation of the Nmp4/CIZ element decreases basal activity of an MMP-13 promoter-reporter construct containing the first 1329 nt of the 5'-regulatory region, and overexpression of Nmp4/CIZ protein enhances the activity of the wild-type promoter. The same mutation of the homopolymeric(dA:dT) element enhances the MMP-13 response to PTH and PGE(2). Overexpression of Nmp4/CIZ diminishes hormone induction. Mutation of both the homopolymeric(dA:dT) element and the adjacent Runx2 site further augments the PTH response. On the basis of these data and previous studies, we propose that Nmp4/CIZ is a component of a multiprotein assemblage or enhanceosome within the MMP-13 PTH response region and that, within this context, Nmp4/CIZ promotes both basal expression and hormonal synergy.

3T3 Cells↗

PubMedDate not supplied

Value of parathyroid hormone assay for preoperative sonographically guided parathyroid aspirates for minimally invasive parathyroidectomy.

PURPOSE: The key to successful parathyroid surgery is accurate preoperative tumor localization. This study investigates the use of ultrasound (US)-guided parathyroid fine needle aspiration (FNA) as a confirmatory diagnostic method in patients with hyperparathyroidism undergoing minimally invasive parathyroidectomy. METHODS: Patients were selected for minimally invasive parathyroidectomy based on the finding of a single parathyroid adenoma identified with US and/or sestamibi scans and confirmation of the suspected parathyroid lesion via FNA and parathyroid hormone (PTH) assay. The value of aspirate obtained from the thyroid gland intraoperatively served as the negative control. RESULTS: A total of 56 tissue FNAs were performed in 27 patients. US detected masses suggestive of parathyroid lesion in all 27 patients, and 31 US-guided FNAs were performed. No complications related to the procedure were noted. Intraoperatively, FNA was performed in the thyroids of 25 patients undergoing minimally invasive parathyroidectomy. Aspirates from lesions subsequently confirmed as having developed from the parathyroid gland had a mean PTH level of 4,677 +/- 123 pg/ml (range, 3,600-5,000 pg/ml), which was significantly higher than thyroid aspirates, which yielded a mean PTH level of 48 +/- 7 pg/ml (range, 5-57 pg/ml). The sensitivity of US and sestamibi scans in the detection of abnormal parathyroid glands was 88% and 77%, respectively. The sensitivity of US-guided FNA in confirming the parathyroid origin of a lesion was 100%. CONCLUSION: US-guided FNA for PTH assay can be performed safely for the confirmation of lesions identified with preoperative US for the selection of patients eligible for minimally invasive parathyroidectomy.

Adenoma↗

PubMed2006

The need for reliable serum parathyroid hormone measurements.

Serum parathyroid hormone (PTH) is a recognized marker of bone remodeling in patients with renal osteodystrophy. However, identification of N-terminal truncated PTH fragments and a new form of PTH that interfere with second-generation PTH assays may be responsible for the great variability of PTH values and the difficulties of implementing the recommendations of the National Kidney Foundation/Kidney Disease Outcomes Quality Initiative.

Animals↗

PubMed1984

[Articular chondrocalcinosis in elderly patients and parathyroid hormone levels].

Serum parathyroid hormone was assayed in 16 elderly patients with primary, roentgenographically proved, articular chondrocalcinosis. Mean value, i.e. 4.10 + 1.16 mUI/ml, was compared to that of a control group of 16 subjects matched for sex and age without chondrocalcinosis, living in the same geriatric institution, i.e. 3.94 + 1.43 mUI/ml. The difference is not significant (t = 0,35). Latent hyperparathyroidism is therefore not demonstrated in primary proved articular chondrocalcinosis in the elderly.

Aged↗

PubMed1993

[Secondary hyperparathyroidism in hospitalized aged patients: apropos of 200 assays of intact parathyroid hormone].

Plasma intact parathyroid hormone (PTH) determinations were performed in 200 elderly patients admitted in a geriatric care unit. Abnormally high levels of PTH were observed in 40 subjects. There was a significant correlation between plasma ionized calcium determinations or creatinine clearance and PTH levels. Subjects with high PTH levels exhibited constantly reduced levels of 25 OH-D3. A calcium and vitamin D supplement, performed in 13 patients, was constantly followed by a decrease of the PTH level.

Aged↗

PubMed1983

Body weight and its effect on immunoreactive parathyroid hormone levels.

Immunoreactive parathyroid hormone (iPTH) levels were measured in 12 obese subjects (140-272% ideal body weight) and 10 normal lean volunteers (93-100% ideal body weight). iPTH values were not significantly different in the two groups and tubular maximum phosphate reabsorption (TmP) was comparable in lean subjects and the 4 obese patients tested. 4 obese subjects were evaluated after an average of 6.7% body weight loss, and neither iPTH levels nor TmP were affected. The data indicate that the biological effects of PTH are not enhanced in the massively obese.

Absorption↗

PubMed1998

Structure-activity relation of NH2-terminal human parathyroid hormone fragments.

Human parathyroid hormone (hPTH) is involved in the regulation of the calcium level in blood. This hormone function is located in the NH2-terminal 34 amino acids of the 84-amino acid peptide hormone and is transduced via the adenylate cyclase and the phosphatidylinositol signaling pathways. It is well known that truncation of the two NH2-terminal amino acids of the hormone leads to complete loss of in vivo normocalcemic function. To correlate loss of calcium level regulatory activity after stepwise NH2-terminal truncation and solution structure, we studied the conformations of fragments hPTH-(2-37), hPTH-(3-37), and hPTH-(4-37) in comparison to hPTH-(1-37) in aqueous buffer solution under near physiological conditions by circular dichroism spectroscopy, two-dimensional nuclear magnetic resonance spectroscopy, and restrained molecular dynamics calculations. All peptides show helical structures and hydrophobic interactions between Leu-15 and Trp-23 that lead to a defined loop region from His-14 to Ser-17. A COOH-terminal helix from Met-18 to at least Leu-28 was found for all peptides. The helical structure in the NH2-terminal part of the peptides was lost in parallel with the NH2-terminal truncation and can be correlated with the loss of calcium regulatory activity.

Amino Acid Sequence↗

PubMed1986

Mid-molecule parathyroid hormone assay comparison.

Parathyroid hormone (PTH) assays are becoming available to clinical chemistry laboratories for in-house use. We evaluated the clinical utility of two mid-molecule PTH assays in comparison to a sensitive but technically demanding component assay. A normal reference population, and an abnormal population including cases of primary and secondary hyperparathyroidism, hypoparathyroidism, and humoral hypercalcemia of malignancy were tested. PTH determinations with each assay system and total serum calcium determinations were done on all specimens. The Endocrine Metabolic Center (EMC) kit assay and the Immuno Nuclear Corp. (INC) kit assay demonstrated adequate standard curve reproducibility and precision for clinical use. With the aid of calcium determinations each assay performed well in the separation of abnormal patient groups, and in the separation of abnormal from normal PTH-calcium homeostasis. PTH values for the reference population differed among the three assays. The component assay and the EMC assay had a negative correlation with serum calcium, but the INC assay had a positive correlation with serum calcium.

Calcium↗

PubMed2006

Serum proteome profiles identifies parathyroid hormone physiologic response.

Parathyroid hormone (amino acids 1-34) (PTH) regulates bone and calcium homeostasis. The magnitude of the effects of PTH on bone varies in osteoporosis patients. We employed ProteinChip technology to generate protein profiles from sera of mice treated once daily with PTH or vehicle for 3 or 11 days. Data analyses on selected arrays indicated significant increases in serum proteins or peptides in PTH-treated groups, compared to vehicle-controls. The magnitude of change increased with duration of treatment. Anion-exchange fractionation of sera prior to profiling on array surfaces increased the number of proteins detected that were regulated by PTH. The optimized purification conditions developed "on-chip" for subsets of proteins, reflected corresponding behavior with process-compatible chromatographic resins under elution chromatography. We have identified and evaluated subsets of serum proteins regulated by PTH treatment, using a combination of ProteinChip technology, column chromatography, PAGE and LC-MS/MS. Our data demonstrate the feasibility of using a panel of serum proteins to detect PTH responsiveness in humans.

Animals↗

PubMed1993

A survey of diagnoses in patients with a low intact parathyroid hormone concentration.

Intact parathyroid hormone (PTH) was analysed in 1107 samples over a 13 month period. Of these, 181 samples (16%) gave results of < or = 1 pmol/L and the case notes of 169 of these 181 patients were examined. Eighty-two patients (48%) were hypercalcaemic at the time of the PTH assay. As expected, the most common diagnosis in this group was hypercalcaemia of malignancy but surprisingly this accounted for only 42 of the hypercalcaemic patients; an unexpectedly high proportion (20 patients) had chronic renal failure with hypercalcaemia due to excessive treatment with 1 alpha-hydroxycholecalciferol; eight patients had transient unexplained hypercalcemia and the remaining 12 patients were hypercalcaemic for a variety of causes including immobilization, bendrofluazide treatment and Paget's disease. Fifty-nine patients (35%) were normocalcaemic: 26 had osteoporosis, 10 had chronic renal failure and the remainder had a wide range of diagnoses. It is possible that the low intact PTH result in a proportion of the normocalcaemic group was caused by ingestion of calcium tablets prior to blood sampling for PTH. Twenty-eight patients (17%) were hypocalcaemic: 24 of these had hypoparathyroidism, two had chronic renal failure and two had transient unexplained hypocalcaemia.

Calcium↗

PubMed1994

Studies on the use of cultured cells in a bioassay for parathyroid hormone.

Measurement of parathyroid hormone (PTH) is important for diagnosing hyper- and hypoparathyroidism. The move to two-site immunometric assays that detect the whole molecule has improved the discrimination of these conditions but these assays may be too restrictive because some PTH fragments that are biologically active may not be detected. In addition, PTH-like peptide of malignancy, an important cause of malignancy-associated hypercalcaemia, is not detected by the two-site assays. Experiments were performed to set up a simple, robust and inexpensive bioassay for PTH, exploiting a kidney cell line and using cyclic AMP or an eluted stain assay as the end point. Of the 12 cell lines tested, an opossum kidney (WOK) cell line showed the most promise. Despite optimization of the procedure to include pre-treatment with dexamethasone, insulin and PTH, followed by incubation in the presence of 5'-guanylimidodiphosphate, isobutyl-1-methylxanthine and forskolin, the WOK cells showed insufficient sensitivity for use in a cultured cell bioassay for PTH in human serum. In addition, the cells were less sensitive to PTH-like peptide precluding their use for an assay for this molecule.

Animals↗

PubMed1981

Rat enterocyte Na+ transport in vitro. Action of parathyroid hormone and calcitonin.

Parathyroid hormone (PTH) and calcitonin exert well known effects on the renal tubule which are thought to involve specific hormone receptors and adenyl cyclase. In the intestine, it is not clear whether the action of PTH and calcitonin is only indirect or also direct, and their mechanisms of action are much less well established. In the present study, possible direct effects of PTH and calcitonin on Na+ transport in isolated intestinal epithelial cells of rats were investigated. In the presence of bovine PTH (1.2 I.U/ml) in the incubation medium, the Na+ efflux rate constant (oKNa) of isolated enterocytes was significantly reduced when compared to that in control experiments with the hormone vehicle only. The mean depression of oKNa induced by bovine PTH was 26% as compared to the control (100%) and to that induced by ouabain (4.0 mM) which was 44%. No depressant effect of bovine PTH on oKNa was observed when the isolated enterocytes were incubated with ouabain (4.0 mM). Thus, bovine PTH appeared to inhibit the ouabain-sensitive Na+ pump. When incubating the isolated epithelial cells in an EGTA-containing CA2+-free medium, bovine PTH lost its capacity to inhibit oKNa. Thus, the presence of extracellular Ca2+ appeared necessary for the inhibitory effect of bovine PTH. In contrast to its effect on oKNa, bovine PTH induced no change in net Na+ uptake by isolated enterocytes. Moreover, no significant effect on enterocyte Na+ transport could be demonstrated for salmon or porcine calcitonin at two different concentrations in the incubation medium, Neither bovine PTH nor salmon calcitonin induced significant changes in enterocyte cyclic AMP or cycle GMP concentrations. It was concluded that bovine PTH, but not calcitonin, exerted a directed inhibitory effect on the ouabain-sensitive oKNa of isolated rat enterocytes. The effect of bovine PTH occurred without measurable activation of the cyclic nucleotide system but needed the presence of Ca2+ in the incubation medium to be operative.

Animals↗