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At least 775 records · Page 43Linked to original sources
PubMed1994

Retinoic acid suppresses parathyroid hormone (PTH) secretion and PreproPTH mRNA levels in bovine parathyroid cell culture.

1,25-dihydroxyvitamin D3[1,25(OH)2D3] suppresses parathyroid hormone (PTH) gene transcription. Recent evidence suggests that retinoid X receptors are involved in 1,25(OH)2D3-mediated transcriptional events. However, little data exists for a role of retinoids in parathyroid function or in PTH expression. In the present study, we observed that all-trans- or 9-cis retinoic acid suppressed the release of PTH from bovine parathyroid cell cultures. Both retinoids were remarkably potent with significant decreases evident at 10(-10) M and a maximally suppressive effect (approximately 65%) at 10(-7) M. All-trans-retinol was considerably less potent in this system. The effect was not evident until 12 h, suggesting that retinoids did not affect the rapid secretion of preexisting PTH stores. PreproPTH mRNA levels were also suppressed by retinoic acid and the retinoid potencies were similar to those observed in the secretion studies. Combined treatment with 10(-6) M retinoic acid and 10(-8) M 1,25(OH)2D3 more effectively decreased PTH secretion and preproPTH mRNA than did either compound alone. These data indicate that retinoic acid: (a) elicits a bioresponse in bovine parathyroid cells; (b) attenuates PTH expression at the protein and mRNA levels, and (c) acts independently of 1,25(OH)2D3 in the control of PTH expression.

Animals↗
PubMed1977

Hypo-hyperparathyroidism: evidence for a defective parathyroid hormone.

Biochemical evidence for hypoparathyroidism and roentgenographic evidence for hyperparathyroidism were present in a 7-year-old girl with seizures and tetany. She was hypocalcemic (4.7 mg/dl), hyperphosphatemic (11 mg/dl), and normomagnesemic, with elevated parathyroid hormone level (2,603 pg/dl and 3,693 pg/dl in immunoassays utilizing two different antisera). Somatic features of pseudohypoparathyroidism were absent. Increased serum alkaline phosphatase activity (335 IU/liter) with evidence of subperiosteal bone resorption suggested parathyroid hormone activity on bone. Intramuscular administration of parathyroid extract caused a rise in serum calcium level (9.6 mg/dl) and a fall in serum phosphorus level (7.9 mg/dl). The serum calcium, phosphorus, and alkaline phosphatase activity became normal during vitamin D therapy. Parathyroid hormone values and bone roentgenograms became normal. With serum calcium and phosphorus levels normal, ethylenediaminetetraacetic acid infusion was followed by an increase in plasma parathyroid hormone level but not in urinary cyclic adenosine monophosphate (AMP) or phosphaturia; in contrast, parathyroid extract induced cyclic AMP excretion and phosphaturia. These results suggest that endogenous parathyroid hormone in this patient affects bone resorption but not renal handling of phosphate. We infer that this represents a defective endogenous parathyroid hormone.

Bone and Bones↗
PubMed1992

Level-dependent inhibitory effect of hyperaluminaemia on parathyroid hormone secretion in patients with end-stage renal failure.

OBJECTIVES: Serum aluminium and parathyroid hormone levels were measured in chronic dialysis patients at discovery of accidental exposure to high dialysate aluminium levels and followed after adequate water purification. PATIENTS AND METHODS: Twenty-nine patients with chronic renal failure on maintenance haemodialysis were accidently exposed to dialysate aluminium levels of 65 micrograms/L (recommended Food and Drug Administration values less than 10 micrograms/L) for 18 months. At discovery, oral aluminium was withdrawn and dialysate aluminium levels were corrected to less than 5 micrograms/L. Serum aluminium, parathyroid hormone, calcium, phosphorus and alkaline phosphatase levels were determined at discovery and two months and one year after the corrective measures. RESULTS: Mean serum aluminium level was 167.6 +/- 15 micrograms/L at discovery and simultaneous serum parathyroid levels were 7.9 +/- 2.2 pmol/L (normal values 1.1 to 4.6 pmol/L). Two months after discontinuation of oral aluminium and correction of dialysate aluminium levels to less than 5 micrograms/L, the patients' mean serum aluminium dropped to 49.6 +/- 4.3 micrograms/L and simultaneous serum parathyroid hormone levels rose to 14.6 +/- 3.2-pmol/L (p < 0.001). Similar levels were maintained at one year. Serum calcium did not change significantly. There was a significant correlation between the drop in serum aluminium and the increase in parathyroid hormone. CONCLUSION: These results confirm animal experiments and show convincingly that aluminium inhibits parathyroid secretion also in humans.

Aluminum↗
PubMed1969

Effects of polypeptide and protein hormones on lipid monolayers. I. Effect of insulin and parathyroid hormone on monomolecular films of monooctadecyl phosphate and stearic acid.

Insulin in low concentrations inhibits the uptake of Ca(++) by the monooctadecyl (stearyl) phosphate monolayer (at air-water interface) and facilitates the release of Ca(++) adsorbed to the monolayer. These effects of insulin are more pronounced at higher insulin concentrations. Evidence is presented that a relatively intact insulin molecule competes with Ca(++) for the free phosphate group of the monolayer. Albumin has a slight inhibitory action on calcium uptake and parathyroid hormone has no observable action on calcium uptake or release.

Albumins↗
PubMed2000

Parathyroid hormone. Does it have a role in the pathogenesis of osteoporosis?

Of the many functions that parathyroid hormone serves, none is more important than its role to maintain calcium homeostasis. Intrinsic to the aging process is changes in the synthesis, metabolism, and responsiveness of parathyroid hormone. This article explores whether the age-associated changes in parathyroid hormone are causally related to the age-associated changes in bone mass. On the other hand, some of the apparent changes in parathyroid hormone associated with aging may be adaptive, serving to protect the aging skeleton. More information is needed to sort out these diametrically opposite views.

Aging↗
PubMed1975

Region-specific immunoassays for parathyroid hormone.

Immunoassays specific for limited regions of bovine parathyroid hormone were developed in four ways. With the heterogeneous antisera produced by immunizing with intact bovine parathyroid hormone (BPTH 1-84), the specificity of radioimmunoassays could be enhanced by presaturating either with an amino-terminal (BPTH 1-34) or carboxy-terminal (BPTH 53-84) fragment. Then, the antibodies which had not been neutralized reacted exclusively with the opposite end of the molecule, even using [125I]BPTH 1-84 as tracer. With some antisera, the appropriate fragment and intact hormone reacted identically. However, with other antisera, the fragment reacted less well than the intact hormone, possibly because these antisera contain antibodies reacting with the middle of the molcule. Using the labelled fragment ([125I]BPTH 1-34) as tracer, with heterogeneous antisera, radioimmunoassays specific for the amino-terminal region were obtained. With one antiserum, BPTH 1.34 reached identically with the intact hormone, but with another antiserum, the fragment was more reactive than the intact molecule. A region-specific radioimmunoassay was also developed using antibodies produced by immunization with a fragment of the hormone. An antiserum raised against BPTH 1-34 had high affinity for the amino-terminal fragement, but reacted less well with the intact hormone. Immunoradiometric assays, specific for the amino- or carboxy-terminal regions, developed by using immunoadsorbents consisting of a fragment (either BPTH 1-34 or BPTH 53-84) coupled to cellulose. These were used to fractionate 125I-labelled antibodies. With some of these selected antibodies, the appropriate fragment was of lower reactivity than the intact hormone. This may have been due to the presence of an incomplete antigenic site on the fragment, or to conformational differences between the fragment and the corresponding region of the intact hormone. With other selected antibodies the fragment and the intact molecule reacted identically. Careful selection of antisera and of technique is necessary to obtain an assay in which a fragment and the intact hormone behave identically.

Animals↗
PubMed1987

Monoclonal antibodies to human parathyroid hormone (1-34) and their use in the immunocytochemical detection of parathyroid tumours.

Monoclonal antibodies against the biologically active N-terminal fragment of human parathyroid hormone, hPTH (1-34), were produced. The procedure included the use of novel secondary immunization in vitro of mouse spleen cell cultures. Dissociated spleen cells from primary immunized Balb/c mice, were cultured for five days in the presence of thymocyte conditioned media (TCM) and synthetic hPTH (1-34). Contrary to previous findings by other workers, in our hands Balb/c mice responded well. Following immunization the spleen cells were fused with NSl myeloma cells and cultured for eleven days before screening for antibody. Using an enzyme linked immunosorbent assay (ELISA) a number of positive clones were detected. Positive cells were cloned by limiting dilution and fifteen specific monoclonal hybridomas were produced. The immunoglobulin class of the different monoclonal antibodies was found to be IgGl. The immunocytochemical reaction was tested with chief cell carcinoma tissue and found to be clearly positive.

Animals↗
PubMed1996

Down-regulation of the receptor for parathyroid hormone (PTH) and PTH-related peptide by PTH in primary fetal rat osteoblasts.

We studied the effects of parathyroid hormone (PTH) on PTH parathyroid hormone related peptide (PTHrP) receptor mRNA level, PTHrP binding and PTH-stimulated cyclic adenosine monophosphate (cAMP) accumulation in osteoblasts, derived from fetal rat calvariae (ROB). Cells isolated during 10-70 minutes of collagenase treatment were seeded at a density of 25,000 cells/cm2 and cultured for 4 days. These cells show a fast increase in cAMP production after stimulation for 5 minutes with 20 nM bovine parathyroid hormone(1-34) (bPTH(1-34)). When ROB are incubated with bPTH(1-34) (0.04-40nM) for 24 h, a dose-dependent decrease of the PTH/PTHrP receptor mRNA level, PTHrP binding, and PTH-stimulated cAMP accumulation can be observed. Pretreatment of ROB with a high concentration of bPTH(1-34) (40 nM) leads within 15 minutes to a decrease in PTH-stimulated cAMP accumulation. However, it takes > or = 3 h before a significant decrease in PTH/PTHrP receptor mRNA level can be observed. Also a significant decrease in PTHrP binding is observed after only 4 h of incubation with bPTH(1-34). Compared with bPTH(1-34), pretreatment of ROB with bPTH(3-34) (40 and 100 nM) for 24 h causes smaller decreases in PTH-stimulated cAMP accumulation, PTHrP binding, and in the PTH/PTHrP receptor mRNA level. We investigated the possible involvement of the protein kinase A signaling pathway in the regulation of the PTH/PTHrP receptor mRNA expression. Both forskolin and (Bu)2cAMP decreased PTHrP binding and PTH/PTHrP mRNA levels. These observations suggest that chronic activation of the PKA signaling pathway may down-regulate PTH/PTHrP receptor expression and thus hormone responsiveness in "normal" osteoblasts. In short, we found that the decrease of the PTH-stimulated cAMP accumulation after long-term pretreatment with bPTH(1-34) is correlated with both PTH/PTHrP receptor mRNA level and PTHrP binding. These data also suggest that the initial desensitization (< 30 minutes) of PTH-stimulated cAMP responsiveness by pretreatment with a high concentration of bPTH(1-34) (40 nM) is not dependent on the number of available PTH/PTHrP receptors. The protein kinase A signaling pathway is involved in the regulation of the PTH/PTHrP receptor, but, regarding the effect of bPTH(3-34), other signaling systems are also involved.

Animals↗
PubMed1975

A reinvestigation of the amino-terminal sequence of human parathyroid hormone.

The sequence of the amino-terminal portion of human parathyroid hormone, particularly the identity of residues 22, 28, and 30 (the subject of discrepancies in recent published reports), has been reexamined by two basic methods of structural analysis. A fresh lot of human parathyroid hormone isolated from pooled adenoma tissue was analyzed by Edman degradation with identification of critical residues by thin-layer chromatography and gas-liquid chromatography. In the second approach, -14C or tritiated amino acids were incorporated during biosynthesis of the human hormone in slices of parathyroid glands in vitro; the appropriate amino acid residues were then determined as the -14C or tritiated phenythiohydantoin derivatives of the amino acid after Edman degradation, or by peptide isolation after appropriate cleavage with endopeptidase, or both. The results confirm our previous findings that residue 22 is glutamic acid, residue 28 is leucine, and residue 30 is aspartic acid.

Adenoma↗
PubMed1983

Lack of rapid effects of cortisol on parathyroid hormone levels in cattle.

Experiments were performed to study plasma concentrations of parathyroid hormone in association with short-term changes of cortisol and dexamethasone. Parathyroid hormone was not significantly modified during 3-hour intravenous infusions of cortisol, leading to marked elevations (p less than 0.001) of plasma cortisol levels, and during intravenous administration of dexamethasone. Thus glucocorticoids, at least in cattle, apparently cause no short-term changes of plasma parathyroid hormone levels.

Animals↗
PubMed1979

Identification of immunoreactive sites in bovine parathyroid cells to antibodies raised against the NH2-terminal sequence of parathyroid hormone.

The NH2-terminal sequence of bovine parathyroid hormone (1-84) was localized with different immunocytochemical methods on the light and electron microscopic level in bovine parathyroid glands and in isolated bovine parathyroid parenchymal cells. The peroxidase labeled staphylococcal protein A and the peroxidase anti-peroxidase method were found to be advantageous for light and electron microscopic localization, respectively. Reaction product was found light microscopically in the cytoplasma of the parenchymal cells and electron microscopically largely over the secretion granules of the parenchymal cells. The immunoreactive sites were subsequently identified to represent only intact parathyroid hormone (1-84) by gel electrophoresis derived enzyme linked immunosorbent assay.

Animals↗
PubMed2003

Gene expression profiles and transcription factors involved in parathyroid hormone signaling in osteoblasts revealed by microarray and bioinformatics.

Parathyroid hormone (PTH) binds to its receptor PTH1R (parathyroid hormone 1 receptor) in osteoblastic cells to regulate bone remodeling and calcium homeostasis. While prolonged exposure to PTH causes increased bone resorption, intermittent injections of PTH have an anabolic effect on bone. The molecular mechanisms regulating these processes are still largely unknown. Here, we present our results on gene expression profile changes in the PTH-treated osteoblastic cell line, UMR 106-01, using DNA microarray analysis. A total of 125 known genes and 30 unknown expressed sequence tags (ESTs) were found to have at least 2-fold expression changes after PTH treatment at 4, 12, and 24 h. 14 genes were previously known to be PTH-regulated but many were unknown to be regulated by PTH prior to our experiments. Real-time reverse transcriptase-PCR confirmed that 90 and 50% of the genes are regulated more than 2-fold by PTH in UMR 106-01 and rat primary osteoblastic cells, respectively. Most genes belong to the following protein families: hormones, growth factors, and receptors; signal transduction pathway proteins; transcription factors; proteases; metabolic enzymes; structural and matrix proteins; transporters; etc. These results provide a comprehensive and deeper knowledge about PTH regulation of osteoblastic gene expression. Next, we designed a computational method to extract information about transcription factors likely involved in regulating these genes. These factors include those previously known to be involved in PTH signaling (AP-1 and the cAMP response element-binding protein), those that were identified by microarray data (C/EBP), and some novel transcription factors (AP-2, AP-4, SP1, FoxD3, etc.). Our results suggest that a reliable bioinformatics approach can be easily applied for other systems.

Animals↗
PubMed1982

Magnesium promotes both parathyroid hormone secretion and adenosine 3',5'-monophosphate production in rat parathyroid tissues and reverses the inhibitory effects of calcium on adenylate cyclase.

Reduced extracellular Ca2+ is known to promote PTH secretion, while severe Mg2+ depletion has the opposite effect. We have correlated the effects of Mg2+ and Ca2+ on parathyroid hormone (PTH) secretion and cAMP accumulation by rat parathyroid tissues in vitro with the effects of these two metals on adenylate cyclase activity in broken membrane preparations. PTH secretion was maximal at 0.5 mM Ca2+, falling to low levels as the Ca2+ concentration was increased to 2.5 mM. Deletion of Mg2+ from the medium resulted in a marked decrease in PTH secretion at any given Ca2+ concentration. At a constant Ca2+ concentration of 1 mM, both PTH secretion and cAMP production rose to maximal rates as the Mg2+ concentration was increased from 0 to 2 mM. The adenylate cyclase of rat parathyroid membranes was stimulated by both GTP and guanyl-5'-yl-imidodiphosphate [Gpp(NH)p]. EDTA-treated membranes could not be stimulated by Gpp(NH)p. Repletion with Mg2+ was more effective than repletion with Ca2+ in restoring responsiveness to the guanine nucleotide. When membranes were maximally preactivated by Gpp(NH)p and then assayed in the presence of variable concentrations of metal ions, enzyme activity was directly inhibited by Ca2+ and stimulated by Mg2+. Adenylate cyclase sensitivity to Ca2+ inhibition was dependent upon the Mg2+ concentration; in the presence of 0.6 mM Mg2+ a 50% inhibition was produced by 0.05 mM Ca2+, while in the presence of 8 mM Mg2+ a 10-fold higher Ca2+ concentration was required for a similar inhibitory effect. The results suggest that Ca2+ may decrease PTH secretion at least in part by a direct inhibition of adenylate cyclase. Mg2+ may promote PTH secretion either by enhancing the activation of adenylate cyclase by endogenous guanine nucleotides or by competing with Ca2+ for binding to a distinct regulatory site on the enzyme.

Adenylyl Cyclase Inhibitors↗
PubMed1988

Fluoride stimulates the accumulation of inositol phosphates, increases intracellular free calcium, and inhibits parathyroid hormone release in dispersed bovine parathyroid cells.

The stimulation of polyphosphoinositide (PPI) turnover is associated with cellular activation and hormone secretion in numerous systems. GTP-binding proteins appear to couple receptors to phospholipase-C-mediated PPI breakdown. We assessed the effects of fluoride, an activator of GTP-binding proteins, on inositol phosphate accumulation, intracellular free Ca2+ [(Ca2+)i], cAMP content, and PTH release in dispersed bovine parathyroid cells. Sodium fluoride (5-30 mM) produced marked dose-dependent increases in inositol phosphates. With anion exchange HPLC, we confirmed that 30 mM fluoride stimulated a rapid increase in 1,4,5-inositol trisphosphate, a potent Ca2+-mobilizing compound. Using the Ca2+-sensitive probe fura-2, we determined that 30 mM fluoride increased [Ca2+]i from 339 +/- 9 to 650 +/- 39 nM (n = 8) within 30-60 sec at 1 mM extracellular Ca2+. After the depletion of extracellular Ca2+ by the addition of 1 mM EGTA, 30 mM fluoride increased [Ca2+]i 45 +/- 9% (n = 4), indicating that fluoride can mobilize intracellular Ca2+ stores. Fluoride (1-30 mM) also inhibited PTH release in dose-dependent fashion. Fluoride (30 mM) produced 72.8 +/- 4.2% suppression of maximal low Ca2+-stimulated PTH release comparable to the 83.7 +/- 3.7% inhibition by 2.0 mM extracellular Ca2+. Since changes in both [Ca2+]i and cAMP regulate PTH release, we measured the effect of fluoride on intracellular cAMP. Fluoride did not detectably change basal cAMP content, but it reduced forskolin-stimulated increases in cAMP. We conclude that fluoride may activate at least two GTP-dependent processes in parathyroid cells, resulting in PPI breakdown and cAMP accumulation. While both may contribute to the fluoride-induced suppression of PTH release, our findings suggest that the stimulation of PPI turnover leads to inhibition of PTH secretion.

Animals↗
PubMed1975

Role of parathyroid hormone in the phosphaturia of extracellular fluid volume expansion.

Role of parathyroid hormone in the phosphaturia of extracellular fluid volume expansion. Acute expansion of the extracellular fluid volume increases the urinary excretion of phosphate. The present study examined the importance of increased plasma parathyroid hormone concentration in the phosphaturia accompanying acute extracellular fluid volume expansion (ECVE). Infusion of a calcium-free Ringer's solution into dogs was associated with increased urinary phosphateexcretion and serum immunoreactive parathyroid hormone concentration (iPTH), the latter being significantly correlated with a decrease in plasma ionized calcium concentration. Prevention of the fall in plasma ionized calcium concentration by infusion of a calcium containing Ringer's solution prevented the increase in serum iPTH but the magnitude of the phosphaturia was not affected.

Animals↗
PubMed1976

Dietary calcium, calcium kinetics and plasma parathyroid hormone concentration in cows.

Kinetic analysis of radiocalcium data was combined with radioimmunoassays of plasma parathyroid hormone in nonpregnant nonlactating cows 4.5 to 7.8 years of age whose calcium intake was varied from 0.05% to 1.4% of the diet. Calcium intake had no significant effect on plasma concentration of calcium or parathyroid hormone. It had a slight but significant effect on the plasma phosphorus concentration. As calcium intake increased, calcium absorption increased but calcium removal from bone decreased so that total calcium transport into the exchangeable pool remained fairly constant. A decline in calcium clearance with age was accompanied by a fall in plasma parathyroid hormone concentration, and a decrease in calcium transport into the pool. These observations are consistent with feedback controls between plasma calcium, parathyroid hormone and calcium transport operating to maintain plasma calcium homeostasis as calcium clearance declined with advancing age.

Age Factors↗
PubMed1995

In vivo parathyroid hormone stimulates in vitro bone resorption by bovine monocytes.

Cells of the monocyte-macrophage lineage have been thought to play a role in bone resorption. We examined the effects of in vivo administration of parathyroid hormone and 1,25-dihydroxyvitamin D3 on the ability of monocytes to degrade bone in vitro. Administration of parathyroid hormone for 4 d resulted in sustained hypercalcemia and a transient 1-d increase in plasma 1,25-dihydroxyvitamin D3. Parathyroid hormone significantly stimulated bone degradation by monocytes 2.6 times more than that of pretreatment controls. Parathyroid hormone treatment significantly enhanced (threefold) release of superoxide anion by monocytes stimulated with phorbol 12-myristate 13-acetate and increased migration of monocytes to bone particles in vitro. Continuous 7-d infusion of 1,25-dihydroxyvitamin D3 (50 micrograms/d) elevated plasma 1,25-dihydroxyvitamin D3 until infusions were discontinued. Increased 1,25-dihydroxyvitamin D3 was associated with hypercalcemia, which continued for several days postinfusion. In vivo administration of 1,25-dihydroxyvitamin D3 did not affect in vitro ability of monocytes to degrade bone. We concluded that in vivo administration of parathyroid hormone enhanced in vitro responsiveness of isolated monocytes in a manner consistent with a role for monocytes in bone remodeling. Furthermore, these data suggested that circulating monocytes could be a useful experimental model for further studies on parathyroid hormone responsiveness and bone resorption for the cow with milk fever.

Animals↗