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At least 649 records · Page 36Linked to original sources
PubMed1983

Effects of ouabain on [3H]ouabain binding, 86Rb uptake, cellular sodium and potassium, and parathyroid hormone secretion in dispersed bovine parathyroid cells.

We have compared the effects of the cardiac glycoside ouabain on [3H]ouabain binding, 86Rb uptake, cellular sodium and potassium, and PTH secretion in dispersed bovine parathyroid cells. [3H]ouabain binds reversibly to a single class of binding sites with an affinity of 6.1 X 10(-8) M and a binding capacity of 5.8 X 10(5) sites/cell. Ouabain also inhibits the uptake of 86Rb, an analog of K, by 90% with half-maximal inhibition at 7.2 X 10(-8) M. There is a concomitant, ouabain-induced increase in cellular sodium and a reduction in cellular potassium. The half-maximal effect on cellular monovalent cations takes place at 1.4 X 10(-7 M ouabain. Finally, ouabain causes a dose- and time-dependent inhibition of low calcium-stimulated PTH secretion. This inhibition does not require extracellular calcium; half-maximal inhibition occurs at 1.1 X 10(-7) M ouabain. These results show that dispersed bovine parathyroid cells contain abundant binding sites for ouabain, a known inhibitor of Na+-K+-ATPase. Moreover, the ouabain-induced reduction in 86Rb uptake and alterations in cellular sodium and potassium support an inhibition of this enzyme in parathyroid cells by the cardiac glycoside. Finally, the close correspondence between ouabain binding and effects on Rb uptake, cellular monovalent cations, and PTH release suggest a role for Na+-K+-ATPase per se or for monovalent cations in PTH secretion. A change in sodium-calcium exchange due to the elevation in cellular sodium is a potential mechanism by which ouabain might inhibit PTH secretion.

Animals↗
PubMed1989

Combined effects of dexamethasone and 1,25-dihydroxyvitamin D3 on parathyroid hormone secretion in cultured bovine parathyroid cells.

The present studies investigate the effects of glucocorticoids on the function of the parathyroid glands using primary cultures of bovine parathyroid cells. Treatment of parathyroid cell cultures with dexamethasone for 48 h caused a dose-dependent stimulation of PTH secretion. The minimal concentration of dexamethasone required for a significant stimulation of PTH secretion was 0.1 nM. The stimulatory effect of dexamethasone on the secretion of PTH was found within 12 h of treatment with 100 nM dexamethasone. The steroids deoxycorticosterone and cortexolone, which do not have glucocorticoid activity were without effect of PTH secretion. Since glucocorticoids may modulate the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in other tissues, additional studies were performed to evaluate the interactions of glucocorticoids and 1,25-(OH)2D3. Addition of 1,25-(OH)2D3 to parathyroid cell cultures for 48 h significantly suppressed PTH secretion. In the presence of dexamethasone, however, 1,25-(OH)2D3 also significantly decreased PTH secretion, although it did not reduce PTH secretion to control levels. The treatment of parathyroid cell cultures with 100 nM dexamethasone did not affect the parathyroid cell content of 1,25-(OH)2D3 receptors. In summary, these studies indicate that glucocorticoids significantly increase the secretion of PTH in vitro. This stimulatory effect can be inhibited by 1,25-(OH)2D3. The parathyroid gland is an additional site of physiological antagonism of glucocorticoids and 1,25-(OH)2D3.

Animals↗
PubMed1996

Relationship among cellular diacylglycerol, sphingosine formation, protein kinase C activity, and parathyroid hormone secretion from dispersed bovine parathyroid cells.

To separate the role of changes in parathyroid diacylglycerol (DG) from other effects of extracellular calcium, we studied the effect of inhibition of DG metabolism on PTH secretion and cellular DG content in acutely dispersed bovine parathyroid cells. R 59 022, an inhibitor of DG kinase, increased cellular DG, but significantly decreased PTH secretion. Particulate protein kinase C (PKC) activity decreased in bovine parathyroid cells incubated at high extracellular calcium or in the presence of R 59 022, which is the opposite of what was observed in the presence of the phorbol ester, phorbol myristate acetate. Sphinganine, a normal cellular product that is a known inhibitor of PKC, significantly inhibited PTH secretion at low extracellular calcium, but had no significant effect at normal or high extracellular calcium. We then measured sphingosine in bovine parathyroid cells incubated with high extracellular calcium or R 59 022. Both conditions were associated with significant elevations of cellular sphingosine. These studies suggest that inhibition of PTH secretion and PKC activity by enhanced cellular DG may result from the activation of an inhibitory second messenger pathway involving the sphingoid lipids.

Animals↗
PubMed2005

Direct in vitro evidence of extracellular Ca2+-induced amino-terminal truncation of human parathyroid hormone (1-84) by human parathyroid cells.

CONTEXT: Although serum calcium (Ca2+) concentration regulates the generation of amino-terminally (N-terminally) truncated forms of human PTH (hPTH) degraded from (1-84)hPTH, no studies have yet reported whether the parathyroid gland itself is responsible for this process. OBJECTIVE: Our objective was to determine the site of N-terminal truncation and its roles in PTH metabolism in parathyroid cells in vitro. METHODS: The effect of extracellular Ca2+ concentration was examined on N-terminal truncation in primary cultured parathyroid cells. The parathyroid glands were obtained from the patients with primary and uremia-associated secondary hyperparathyroidisms who underwent therapeutic parathyroidectomies. RESULTS: The N-terminally truncated fragments were detectable with commercially available intact PTH (I-PTH) assays, but not with the bio-intact PTH (Bio-PTH) assay, which detected only the (1-84)hPTH. HPLC revealed that generation of N-terminally truncated fragments detectable by I-PTH increased with extracellular Ca2+ concentration. Suppression of PTH secretion by increasing the extracellular Ca2+ concentration was more evident with the Bio-PTH assay than with the I-PTH assay for both cultured parathyroid cells prepared from parathyroid adenomas and uremia-associated secondary hyperparathyroidism. The Bio-PTH/I-PTH ratio, which is the ratio of (1-84)hPTH to the sum of (1-84)hPTH and N-terminally truncated fragments, decreased in response to increases in extracellular Ca2+. CONCLUSIONS: These findings suggest that the N-terminal truncation is regulated by extracellular Ca2+ concentration and works to suppress the generation of (1-84)hPTH in parathyroid cells.

Calcium↗
PubMed1978

Human parathyroid cryopreservation: in vitro testing of function by parathyroid hormone release.

The functional viability of cryopreserved human parathyroid tissue was assessed by determining suppressibility of parathyroid hormone release by evaluation of ambient calcium concentration. Parathyroid hormone release from dispersed human parathyroid cells prepared from both fresh tissue and tissue cryopreserved for up to 200 days was suppressed 0-90% in response to four-fold increases in calcium concentration. In the tissue that demonstrated suppression precryopreservation, the suppression curve was similar in form postcryopreservation. The ability to retain functional integrity within human parathyroid cells by cryopreservation, allows preservation for periods of time probably sufficient to determine the presence of the aparathyroid state, and allows for subsequent successful parathyroid autotransplantation. This technique has particular applicability to patients reoperated upon for persistent hyperparathyroidism where the remaining amount of normal parathyroid tissue is obscure or unknown.

Calcium↗
PubMed1981

Parathyroid hormone: chemistry and structure-activity relations.

Peptide synthesis and the application of a wide range of biological assays have permitted intensive and detailed study of structure-activity relations for parathyroid hormone. Within the structure of the hormone molecule reside largely distinct domains critical for receptor binding or activation of adenylate cyclase in addition to receptor binding. Subtle modifications of hormonal structure can cause striking changes in hormone potency or in the nature of the biological properties displayed by such analogs. For parathyroid hormone, structure-activity studies have identified several discrete regions of the molecule that are responsible for independent biological functions. It was determined that these separate functions are displayed in an almost linear fashion along the primary sequence of the hormone--a conceptual framework that has greatly facilitated synthesis of parathyroid hormone analogs. The amino-terminal region of the initially biosynthesized precursor form of parathyroid hormone, pre-proparathyroid hormone, - 31 through - 7, contains a leader or signal sequence. Despite differences in sequence of the parathyroid hormone signal region and other precursor-specific sequences, this region of the molecule possesses biological properties related to intracellular transport and metabolism that appear to be universal for precursor forms of many, if not all, peptide hormones and other secreted proteins. In contrast, the amino-terminal portion of the secreted form of the molecule, sequence region 1-34, has an amino acid sequence that is homologous to that of several peptide hormones, including ACTH, alpha-MSH, beta-MSH, and beta-lipotropin. Yet the biological "message" conveyed by this peptide sequence appears unique to parathyroid hormone. Directions have now been established for the design of hormone inhibitors and for analogs of enhanced biological activity and perhaps even analogs possessing an altered spectrum of biological properties. The rapid advances that are occurring in techniques for peptide synthesis, purification, and analysis; in the variety, sensitivity, and specificity of the increasing number of bioassays; and in the elucidation of peptide and protein conformation may provide further important new directions for analog design. Extension of these investigations of structure and function over the next several years should yield a more sophisticated understanding of the mode of hormone action. In such studies lies the promise of generating highly refined and perhaps clinically useful analogs of parathyroid hormone.

Adenylyl Cyclases↗
PubMed1991

[Detection of calcitonin and parathyroid hormone in the human placenta].

Detection of calcitonin and parathyroid hormone in the human placenta at term. In this investigation we proved immunoreactive calcitonin and immunoreactive parathyroid hormone in the maternal side of the human placenta. We used the immunocytochemical staining technique (Peroxidase-Antiperoxidase-method) by Sternberger where different antibodies react. We could see calcitonin and parathyroid hormone mainly in the decidual cells as well as in the cytotrophoblastic cells of the maternal part of the placenta.

Calcitonin↗
PubMed1992

Role of assays for parathyroid-hormone-related protein in investigation of hypercalcaemia.

Parathyroid-hormone-related protein (PTHrP) has been implicated as a humoral mediator of hypercalcaemia in malignant disease. We have investigated the contributions of PTHrP and parathyroid hormone (PTH) to the hypercalcaemia seen in routine clinical practice by means of highly sensitive immunoradiometric assays. PTHrP concentrations in plasma and PTH concentrations in serum were measured in 121 consecutive patients with hypercalcaemia (corrected serum calcium above 2.65 mmol/l) identified from routine biochemical profiles in a district general hospital. Hypercalcaemia was due to primary hyperparathyroidism in 63 (52%) patients and to malignant disease in 40 (49%). Plasma PTHrP was detectable in 35 (88%) of 40 patients with solid tumours and 3 of 9 patients with haematological malignant disease; it was undetectable in 92% of patients with primary hyperparathyroidism. 7 patients with malignant disease had PTH concentrations above 4.0 pmol/l, consistent with coexisting primary hyperparathyroidism. Measurement of both PTH and PTHrP in all patients led to a change in the diagnosis in 7% of patients. This study provides direct evidence for a humoral role of tumour-derived PTHrP in hypercalcaemia, and shows how PTHrP assays can be used appropriately, in conjunction with PTH assays, to investigate hypercalcaemia in routine clinical practice.

Biomarkers↗
PubMed1992

Regulation of ornithine decarboxylase by parathyroid hormone in osteoblastic cell systems.

Parathyroid hormone (PTH) has been shown to induce osteoblastic activity via a complex signal transduction process which is mediated either by cAMP or cytosolic calcium ([Ca2+]i), or a combination thereof. One of the PTH functions in osteoblasts is the induction of ornithine decarboxylase (ODC) activity. We have analyzed the second messengers involved in this process. 8-Bromo cAMP, a cAMP derivative, enhanced ODC activity in UMR106-01 osteoblastic cell system. The calcium ionophore A23187 and the protein kinase stimulator phorbol-12-myristate 13-acetate did not alter ODC activity. ODC activity was increased by bPTH-(1-34), PGE1, and PGE2 which stimulated both cAMP and [Ca2+]i. In contrast, PTH-(2-34), propionyl bPTH-(2-34), bPTH-(3-34), bPTH-(7-34), and PGF2 alpha, which only enhanced [Ca2+]i but not cAMP, had no effect on ODC activity. Thus, the stimulation of ODC in UMR106 cells by PTH appeared to be mediated primarily via the cAMP signal transduction pathway, and the mere increase in intracellular calcium could not account for the stimulation of ODC activity. ODC mRNA level was found to be increased by PTH treatment. Therefore, translation of ODC may be stimulated by PTH. Moreover, PTH also stimulated ODC antizyme activity, suggesting that the ODC degradation rate was increased.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1975

Comparative response to parathyroid hormone in hyperthyroidism and hypothyroidism.

The effects of exogenous parathyroid hormone, administered for 3 days, were compared in six hyperthyroid and six hypothyroid subjects. Maximum increments were much greater in hyperthyroid than in hypothyroid subjects for serum calcium (3.5 mg/100 ml versus 1.6 mg/100 ml), urine calcium (476 mg versus 79 mg), urine hydroxyproline (56 mg versus 11 mg), and urine phosphorus (671 mg versus 192 mg). Maximum decrease in serum phosphorus (minus0.9 mg/100 ml versus minus 0.1 mg/100 ml) was also greater in hyperthyroid subjects. Serum parathyroid hormone immunoreactivity was significantly higher in hypothyroid subjects (0.48 ng/ml) that either normals (0.21 ng/ml) or hyperthyroid subjects (0.19 ng/ml). The data support the concept that excess thyroid hormone sensitizes and deficient thyroid hormone blunts the responsiveness of bone to parathyroid hormone. This may lead to a state of hypoparathyroidism in hyperthyroidism and hyperparathyroidism in hypothyroidism.

Adult↗
PubMed1973

Binding of parathyroid hormone to bovine kidney-cortex plasma membranes.

1. Plasma membranes were purified from bovine kidney cortex, with a fourfold increase in specific activity of parathyroid hormone-sensitive adenylate cyclase over that in the crude homogenate. The membranes were characterized by enzyme studies. 2. Parathyroid hormone was labelled with (125)I by an enzymic method and the labelled hormone shown to bind to the plasma membranes and to be specifically displaced by unlabelled hormone. Parathyroid hormone labelled by the chloramine-t procedure showed no specific binding. (75)Se-labelled human parathyroid hormone, prepared in cell culture, also bound to the membranes. 3. Parathyroid hormone was shown to retain biological activity after iodination by the enzymic method, but no detectable activity remained after chloramine-t treatment. 4. High concentration of pig insulin inhibited binding of labelled parathyroid hormone to plasma membranes and partially inhibited the hormone-sensitive adenylate cyclase activity in a crude kidney-cortex preparation. 5. EDTA enhanced and Ca(2+) inhibited binding of labelled parathyroid hormone to plasma membranes. 6. Whereas rat kidney homogenates were capable of degrading labelled parathyroid hormone to trichloroacetic acid-soluble fragments, neither crude homogenates nor purified membranes from bovine kidney showed this property. 7. Binding of parathyroid hormone is discussed in relation to metabolism and initial events in hormone action.

Adenylyl Cyclases↗
PubMed1988

Parathyroid hormone and calcium. A relationship in hypertension.

Total and ionized calcium, parathyroid hormone, calcitonin, and renin activity were measured in 27 untreated patients with essential hypertension. There was no relationship between any of these parameters and diastolic blood pressure. However, a significant inverse relationship was found between diastolic blood pressure and the ratio of either total or ionized calcium to parathyroid hormone (r = -0.40, P less than 0.05; and r = -0.38, P less than 0.05, respectively). The ratios did not correlate with patient age or plasma renin level. This preliminary finding suggests that the role of plasma calcium in hypertension may need to be analyzed in the context of overall calcium metabolism, as influenced by the parathyroid hormone. The role of an altered relationship between plasma calcium level and parathyroid hormone in the pathophysiology of essential hypertension remains to be studied.

Blood Pressure↗