Search PubMed⌕ Search

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.

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

At least 1,135 records · Page 63Linked to original sources
PubMed1999

Development of a photoreactive parathyroid hormone antagonist to probe antagonist-receptor bimolecular interaction.

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) exert their calciotropic activities by binding to a specific seven-transmembrane-helix-containing G protein-coupled receptor mainly located in bone and kidney cells. In order to map in detail the nature of hormone-receptor interaction, we are employing 'photoaffinity scanning' of the bimolecular interface. To this end, we have developed photoreactive benzophenone (BP)-containing PTH analogs which can be specifically and efficiently cross-linked to the human (h) PTH/PTHrP receptor. In this report, we describe the photocross-linking of a BP-containing PTH antagonist, [Nle8,18,D-2-Nal12,Lys13(epsilon-BP),2-Nal23,Tyr34]bPT H(7-34)NH2 (ANT) to the recombinant hPTH/PTHrP receptor stably expressed in human embryonic kidney cells (HEK-293, clone C-21). This photoreactive antagonist has high affinity for the hPTH/PTHrP receptor and inhibits agonist-induced cyclase activity and intracellular calcium release. The photo-induced cross-linking of the radioiodinated antagonist (125I-ANT) to the recombinant hPTH/PTHrP receptor followed by SDS-PAGE analysis reveals a single radiolabeled band of approximately 85kDa, similar to that observed after cross-linking of a radioiodinated BP-containing agonist. The formation of this covalent 125I-ANT - hPTH/PTHrP receptor conjugate is competed dose-dependently by a variety of unlabelled PTH- and PTHrP-derived agonists and antagonists. This is the first report of a specific and efficient photocross-linking of a radioiodinated PTH antagonist to the hPTH/PTHrP receptor. Therefore, it provides the opportunity to study directly the nature of the bimolecular interaction of PTH antagonist with the hPTH/PTHrP receptor.

Amino Acid Sequence↗
PubMed1984

[Mechanism of the hypotensive effect of parathyroid hormone].

Intravenous injection of parathyroidine to intact rats in a dose of 2 Units/100 g bw provoked a hypotensive effect. The blockade of alpha-adrenoreceptors did not change the effect of parathyroid hormone. The stable analog of leu-enkephalin inhibited the parathyroidine-induced increase in cAMP level in the vascular wall with no influence on the hypotensive action of parathyroid hormone. Since the hypotensive action of parathyroidine was blocked with isoptin, it is concluded that parathyroid hormone primarily influences sodium-calcium metabolism in the vascular wall.

Adrenergic alpha-Antagonists↗
PubMed2003

Co-expression of parathyroid hormone and chromogranin A in secondary hyperparathyroidism: a functional marker for secretory activity of hyperplastic nodules.

The relationship between secretion of parathyroid hormone (PTH) and biologic characteristics, including cell proliferation or monoclonality, is not yet fully understood. To evaluate secretory activity of glands or nodules histopathologically, we focused on the co-expression of chromogranin A (CgA) and parathyroid hormone (PTH) in each gland or nodule. A total of 55 glands from 38 patients with normal parathyroid glands, hyperplastic glands (diffuse and nodular) and primary adenomas were compared. Co-expression of PTH and CgA was decreased to 44.4% in diffuse hyperplastic glands, and to 39.6% in 91 hyperplastic nodules, in contrast to normal glands and primary adenomas that showed constant co-expression of PTH and CgA. Immunohistochemical study of PTH showed a coarse granular pattern predominantly in PTH-positive/CgA-positive nodules, and a dot-like pattern mainly in PTH-positive/CgA-negative nodules. Laser scanning microscopy and immunoelectron microscopy confirmed that a dot-like pattern is based on a positive reaction of PTH at the Golgi apparatus. MIB-1 LI was 12.6 +/- 11.6 in PTH-positive/CgA-positive, and 19.3 +/- 27.3 in PTH-positive/CgA-negative nodules. In conclusion, a combination of PTH and CgA could provide more information about the physiologic state of secretory activity of each nodule than does the simple observation of PTH immunoreactivity.

Adenoma↗
PubMed1999

Effect of intermittent administration of parathyroid hormone on fracture healing in ovariectomized rats.

To evaluate the potential use as a therapeutic agent for osteoporotic fractures, we examined the effects of intermittent administration of parathyroid hormone on fracture healing in ovariectomized rats. At three months post-ovariectomy, bilateral tibial shaft fractures were induced and stabilized by intramedullary nailing with Kirschnerwires. Saline, 17-estradiol, or recombinant human PTH(1-84) was given once a day for 30 consecutive days during fracture healing. Fracture healing was assessed by morphometric and mechanical analysis of fracture callus. Intermittent parathyroid hormone administration increased the morphometric and mechanical parameters in a dose-dependent manner. 17-estradiol, a bone-resorption inhibiting agent, did not offer advantage in terms of fracture healing in ovariectomized rats. Our findings suggest that intermittent parathyroid hormone administration may benefit osteoporosis and fracture.

Animals↗
PubMed1989

Parathyroid hormone stimulates prostanoid formation in mouse calvarial bones.

Bovine parathyroid hormone (bPTH 1-34) caused a time- and dose-dependent enhanced formation of the two prostanoids PGE2 and 6-keto-PGF1 alpha in cultured neonatal mouse calvarial bones, with threshold for action at 0.1 nmol/l. The PGE2 response to PTH was completely blocked by indomethacin, but insensitive to calcitonin. By contrast, indomethacin was without effect on 45Ca release induced by PTH. The PTH analogues (Nle 8, 18, Tyr 34)-bPTH (3-34) amide and (Tyr 34)-bPTH (7-34) amide, which are putative PTH antagonists, did not affect basal production of PGE2, nor did the analogues affect bPTH 1-34 induced PGE2 formation. The data show that PTH stimulates prostanoid formation in mouse bone cells and that this response is not directly linked to PTH-induced bone resorption.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Optimizing efficacy of quick parathyroid hormone determination in the operating theater.

The usefulness of intraoperative parathyroid hormone (PTH) monitoring has been extensively documented in primary hyperparathyroidism (HPT), whereas few data have been published on its use in reoperations or in secondary and tertiary HPT. We report our initial experience with a rapid (12 min response) PTH immunochemiluminometric assay performed in the operating room during surgery in 12 patients with primary HPT, 16 end-stage renal disease patients with secondary HPT and five kidney transplanted subjects with tertiary HPT. Blood samples were taken at baseline, within 10 min after resection and subsequently at various intervals whenever needed. The mean PTH levels before and after parathyroidectomy were 230.5 pg/mL (range 69-842) and 47.3 pg/mL (range 5-184), respectively, in primary HPT, 855.0 pg/mL (416-1655) and 202.2 pg/mL (53-440) in secondary HPT, and 205.6 pg/mL (116-301) and 45.4 pg/mL (18-97) in tertiary HPT. All patients but one had a significant percentage decline from pre-excision values (mean 76.9%, 76.0%, and 76.1% in primary, secondary and tertiary HPT, respectively). While a reduction of more than 50% was observed in 30 out of 33 patients after the first intraoperative sampling, additional measurements were performed in 10 cases. On-site PTH monitoring with this user-friendly and reliable system has proved helpful in targeting PTH tests to give the surgeon a rapid and accurate assessment of the intervention. The development of optimal PTH sequence strategies with decision-focused analytical and clinical limits will improve the efficacy of "point-of-care" PTH assay and resource utilization.

Adenoma↗
PubMed1975

[Exocrine pancreatic function and calcium balance. Experimental studies of the effect of parathyroid hormone, vitamin D3, 25-hydroxycholecalciferol, dihydrotachysterin and thyrocalcitonin (author's transl)].

The effect of the acute elevation of extracellular calcium concentration, of vitamin D3, 25-hydroxycholecalciferol, dihydrotachysterin, parathyroid hormone and of thyrocalcitonin on the exocrine function of the perfused cat pancreas was studied. Elevation of the perfusate calcium concentration resulted in an initial increase in the enzyme and, occasionally, calcium concentration of the pancreatic juice, the flow rate and the secretion of magnesium and chloride were not very much altered. The application of vitamin D3 and 25-hydroxycholecalciferol elevated the stimulated (by acetylcholine or cholecystokinin-pancreocymin) protein and enzyme output (lipase, alpha-amylase). Parathyroid hormone and, especially, thyreocalcitonin inhibited the stimulated protein and enzyme secretion, volume and rate of the electrolyte secretion were not changed. In states of calcium excess the stimulated protein output was decreased by both vitamin D3 and parathyroid hormone.

Acetylcholine↗
PubMed1992

Structural elements of human parathyroid hormone and their possible relation to biological activities.

Human parathyroid hormone (hPTH) and several deletion analogues were examined for the presence of secondary structure using circular dichroism spectroscopy. The spectra of hPTH and the deletion analogues 8-84, 34-53, 53-84, 1-34, 13-34, 1-19, and 20-34, in neutral, aqueous buffer, gave no evidence for extensive secondary structure. An alpha-helical-like spectral contribution was found to arise from a region within peptide 13-34. This spectral contribution was speculated to arise from partial stability of a helix consisting of residues 17-29. Molecular dynamics simulations of peptide 1-34 suggested that this peptide tends to fold with a bend defined by residues 10-14, with the amino-terminal and carboxyl-terminal residues tending to be in more extended forms and the other residues in helical-like conformations. The addition of trifluoroethanol promoted the formation of alpha-helix, mainly in the 1-34 region. The putative helix comprised of residues 17-29 was stabilized by the addition of 10-20% TFE, while a second putative helix proximal to the amino terminus, and comprised of residues 3-11, was stabilized by slightly higher concentrations of TFE. An amphiphilic sequence was identified within the 20-34 fragment. The development of alpha-helix on binding this fragment, and other analogues containing this sequence, to palmitoyloleoylphosphatidylserine vesicles provided experimental evidence for the potential role of this amphiphilic sequence in binding to membranes or to a membrane receptor. The relationships between these alpha-helical regions in 1-34, either potentiated by trifluoroethanol or lipid vesicles, are discussed in terms of different receptor-binding regions within hPTH.

Amino Acid Sequence↗
PubMed1990

[Rapid measurement of human parathyroid hormone-(1-84) by immunoradiometric assay for use in intraoperative determination of hyperfunctioning parathyroid glands].

Rapid measurement of serum intact parathyroid hormone concentration was achieved by modification of an immunoradiometric assay for the hormone. Incubation of serum samples for 15 min at 37 degrees C under shaking gave optimal results in terms of assay variance and reproducibility: intra-assay CVs were less than 10% over the hormone concentrations of 11-1,600 pg/ml; intra- and inter-assay CVs for two control sera at different hormone levels were less than 12%. The minimal detectable hormone concentration was found at 27.8 pg/ml. The serum hormone levels of 43 subjects (31 health subjects, 9 patients with primary hyperparathyroidism, and 3 patients with secondary hyperparathyroidism) determined by either rapid or regular assay well correlated with each other (r2 = 0.979, p less than 0.001). In two patients with parathyroid adenoma serum intact PTH levels fell rapidly to 12.1% of the preoperative values 20 min after ligation of the vascular pedicle to the hyperfunctioning glands. We conclude that the modified assay protocol allows rapid, accurate, and simple estimation of intact PTH concentrations, and can be used as an intraoperative measure to aid both diagnosis and surgical cure of hyperparathyroidism.

Chi-Square Distribution↗
PubMed1976

Effects of bone in vitro of bovine parathyroid hormone and synthetic fragments representing residues 1-34, 2-34 and 3-34.

The biological activities of bovine parathyroid hormone (BPTH) and fragments comprising portions of its amino-terminal sequence have been compared in three different assay systems using embryonic rat bone in vitro. Whereas the 3-34 fragment was without significant activity the 1-34 fragment caused all the actions characteristic of BPTH 1-84, extending to bone previous evidence that the amino-terminal residues are sufficient for expression of the biological effects of intact parathyroid hormone. However, the relative potencies of the fragment and the intact hormone were different in the various systems. BPTH 1-34 showed relatively low osteolytic activity and induced anabolic effects in both osteoblasts and cartilage cells of cultivated embryonic mouse radii which were not evoked by the intact hormone. Further work is required to determine the mechanisms responsible for these interesting alterations in relative potency of fragment and native hormone.

Animals↗
PubMed1991

Circulating levels of biologically active and immunoreactive intact parathyroid hormone in human newborns.

We evaluated circulating levels of biologically active and immunoreactive intact parathyroid hormone [iPTH-(1-84)] in 47 newborns at birth and eight hypocalcemic preterm infants during the first 10 d of life. Use of two sensitive detection systems, the cytochemical bioassay and an immunoradiometric assay specific for intact parathyroid hormone, enabled us to compare plasma concentrations of PTH-like bioactivity (bioPTH) and iPTH-(1-84). Mean umbilical venous plasma bioPTH was elevated in nondiabetic term and preterm newborns [22.5 +/- 3.1 (+/- SEM) and 15.8 +/- 2.5 ng-equiv/L, respectively] compared with normal adult subjects (9.8 +/- 2.6 ng-equiv/L; p less than 0.01). Umbilical bioPTH was suppressed in five term infants of diabetic mothers (2.6 +/- 0.4 ng-equiv/L). In contrast, iPTH-(1-84) was low in term and preterm nondiabetic infants' and term infants of diabetic mothers' umbilical samples (5.4 +/- 1.5, 4.3 +/- 1.5, and 2.4 +/- 1.0 ng/L, respectively). Umbilical venous bioPTH was highly correlated with the magnitude of the transplacental calcium gradient (r = 0.90; p less than 0.05). In eight preterm infants studied longitudinally, by 24-36 h of life, declining plasma total and ionized calcium (1.71 +/- 0.04 and 0.78 +/- 0.03 mmol/L, respectively) were accompanied by a significant rise in both bioPTH (41.2 +/- 6.3 ng-equiv/L) and iPTH-(1-84) (56.3 +/- 11.6 ng/L). These data indicate that the 3rd trimester fetoplacental circulation contains levels of bioPTH several-fold higher than those of immunoreactive intact hormone. We also conclude that even hypocalcemic preterm newborn infants can significantly elevate circulating levels of PTH.

Adult↗
PubMed1975

[Influence of parathyroid hormone and heparin on tooth development in mice homozygous for the microphthalmia mutation].

In mice, homozygous by microphthalmia (mi/mi) gene the disturbance of dental development was due to defects in dental pulp and to the absence of bone resorpion. Administration of heparin or parathyroid hormone stimulated dental eruption in mi/mi mice. Following combined action of heparin and parathyroid hormone the number of erupted teeth was practically the same as after the action of heparin alone. Possibly the level of heparin is insufficient, but secretion of parathyroid hormone is unimpaired in mi/mi mice.

Animals↗
PubMed1983

Responsiveness of vitamin D-deficient fetal rat limb bones to parathyroid hormone in culture.

Radii and ulnae from 19-day fetal rats from normal or vitamin D-deficient mothers were treated with 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, or parathyroid hormone in vitro. Both sets of bones resorbed in response to all three agents. Statistical analysis indicated a purely additive model for the effects of vitamin D status and the bone-resorbing agents, with no evidence for interaction. The results suggest that the impaired calcemic response to parathyroid hormone seen in vitamin D-deficient animals in vivo is not the result of a specific unresponsiveness of vitamin D-deficient bone to parathyroid hormone.

Animals↗
PubMed1974

Parathyroid hormone effects in rats treated with diphosphonate.

The ability of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP; 40 milligrams per kilogram of body weight per day) to reduce the hypercalcemic effect of parathyroid hormone in thyroparathyroidectomized rats was confirmed. However, treatment with this large dose of EHDP enhanced the hypophosphatemic effect of a low dose of parathyroid hormone (10 international units per100 grams of body weight), apparently by promoting the renal excretion of phosphate. The data suggest that EHDP may have a direct effect on the renal action of parathyroid hormone and, in this way, may also affect vitamin D metabolism by the kidney.

Animals↗
PubMed1992

The relationship between adenoma weight and intact (1-84) parathyroid hormone level in primary hyperparathyroidism.

The relationship between preoperative serum levels of intact parathyroid hormone (PTH), serum calcium, and the weight of parathyroid adenoma has been investigated in 44 patients undergoing surgery for primary hyperparathyroidism due to single gland disease. There was no significant correlation between preoperative serum calcium and either intact PTH concentration or adenoma weight (r = 0.465 and 0.381, respectively). Although there was a significant correlation between PTH concentration and adenoma weight (r = 0.850, p less than 0.0005), this correlation was lost when two unusually heavy adenomas weighing 10.98 and 15.23 g were removed from the analysis. Clearly, a preoperative direct prediction of gland weight determined from PTH level was not possible. Patients with adenomata heavier than 750 mg had a significantly lower circulating PTH level per mg of adenoma than patients with glands lighter than 750 mg. PTH secretion in vitro in low calcium medium by adenoma cells from glands weighing less than 1 g was higher than secretion by cells from adenomas heavier than 1 g. Larger parathyroid adenomata appear to secrete less PTH per unit weight in vivo and per unit cell in vitro under conditions of maximal stimulation.

Adenoma↗
PubMed1981

Parathyroid hormone: a determinant of posttransplant blood pressure regulation.

Persistent hyperparathyroidism and its attendant hypercalcemia have been implicates as possible etiologic factors in posttransplant hypertension. To better define the role of parathyroid hormone (PTH) and calcium in posttransplant blood pressure homeostasis, we measured the acute response of blood pressure, ionized calcium (Ca++), plasma renin activity (PRA), and parathyroid hormone (PTH) to a 4-hr infusion of calcium (15 mg/kg) and an isoproterenol injection (0.15 mg SC) in seven normal subjects and 13 renal transplant (Tx) recipients with stable graft function and persistent hyperparathyroidism. Transient hypercalcemia produced a significant (p less than 0.01) increase in the systolic blood pressure (delta SBP) and suppression of PTH (p less than 0.001) in the posttransplant subjects. There was a significant (p less than 0.02) inverse correlation between changes (delta) in PTH and delta SBP in these subjects. There was no correlation between the delta SBP and either the change in Ca++ (delta Ca++) or the change in PRA (delta PRA) observed in the Tx recipients administered calcium. Following isoproterenol administration, SBP increased (p less than 0.01), PTH fell (p less than 0.05) and Ca++ was only minimally increased in the Tx recipients. A virtually identical, significant (p less than 0.05) inverse correlation existed between the delta PTH and delta SBP observed in the transplant subjects. Greater suppression of PTH was associated with a larger increase in systolic blood pressure. Transient hypercalcemia of comparable degree in normal subjects caused an insignificant increase in their blood pressure. The fact that PTH suppression in the normals was substantially (0.01) less (delta PTH -13 microliter/Eq/ml versus -65 microliter/Eq/ml in the transplant group) with a similar increase in serum calcium suggests that the blood pressure response to transient hypercalcemia is more dependent on PTH suppression than the level of ionized calcium. Plasma renin activity was unchanged during the blood pressure fluctuations induced by either the calcium or the isoproterenol administration to the normal subjects. Under the conditions of this study, endogenous parathyroid hormone has the characteristics of a vasodepressor hormone and may have a role in blood pressure regulation in transplant recipients with hyperparathyroidism. Since the vasodepressor effect can be dissociated from delta Ca+ and delta PRA, such a conclusion seems warranted. The implications of these findings for all subjects with renal disease requires further investigation.

Blood Pressure↗
PubMed1994

Human parathyroid hormone: efficient synthesis in Escherichia coli using a synthetic gene, purification and characterization.

Human parathyroid hormone is a peptide hormone consisting of 84 amino acid residues. Production of small proteins by direct expression in Escherichia coli is often unsuccessful owing to susceptibility of the mRNA and/or the product to endogenous enzymes. In this study, direct expression of the hormone at an excellent level (over 100 mg/L) has been achieved by using a suitably designed synthetic gene under the control of the T7 promoter. The protein produced in bacteria was extracted and easily purified in a good yield of 27 mg/L. The purified product was physico-chemically identified as intact human parathyroid hormone from the results of amino acid analysis, N-terminal sequencing, and peptide mapping using fast atom bombardment mass spectrometry. In biological assays the purified product stimulated adenylate cyclase in vitro, promoted bone growth and increased the serum osteocalcin in rats to the same extent as the authentic hormone.

Amino Acid Sequence↗
PubMed1986

Responsiveness of mouse calvaria to parathyroid hormone after explant cryopreservation: 45Ca release in vitro.

Newborn mouse calvaria prelabeled with 45Ca and cryopreserved at -196 degrees C in serum-free medium containing dimethylsulfoxide were compared to unpreserved explants for response to parathyroid hormone during subsequent culture. After short-term cryopreservation followed by rapid thawing, the viable explants continued to release 45Ca to the culture medium but additions of parathyroid hormone to the medium did not cause increased bone resorption. The data suggest that cryopreservation and thawing impairs mechanisms responsible for parathyroid hormone action on bone cells.

Animals↗