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At least 19 recordsLinked to original sources
PubMed1992

Relationships of parathyroid hormone, parathyroid secretory protein, parathyroid hormone messenger RNA, parathyroid secretory protein mRNA, and replication in human parathyroid adenoma and secondary hyperplasia tissues and cultures.

BACKGROUND: The purpose of this study was to clarify the relationships of extractable and secreted parathyroid hormone (PTH) and parathyroid secretory protein (PSP) in human parathyroid tumors to PTH messenger RNA (mRNA), PSP mRNA, and cell replication. METHODS AND RESULTS: In tissue cultures of seven adenomas and five secondary hyperplasias, we found a direct correlation for secreted PTH versus PSP for both adenomas and secondary hyperplasias. Secreted PTH:PSP was elevated for adenomas (11:1) compared to that of secondary hyperplasias (2:1), and adenomas secreted significantly more PTH and PSP than did secondary hyperplasias. In extracts of eight adenomas and six secondary hyperplasias, the ratio of PTH:PSP was unexpectedly low (2:1) and similar for both adenomas and secondary hyperplasias. The ratio of extractable PTH mRNA:PSP mRNA was extremely low for both adenomas (1:7) and for secondary hyperplasias (1:5). Flow cytometry indicated that percent replication was inversely correlated with PTH mRNA and PSP mRNA. CONCLUSIONS: Increased PTH secretion by adenomas cannot be attributed to increased biosynthetic capacity because it is less than expected. Hypersecretion of PTH by adenomas and coincident marked reductions in PTH mRNA suggest either a defect in cytoplasmic storage of PTH or impairment of normal posttranslational degradation of PTH. As parathyroid tumor cells increase replication, PTH mRNA is reduced. Possible explanations for this include decreased PTH gene transcription or decreased mRNA half-life.

Adenoma↗
PubMed2000

Six-month daily administration of parathyroid hormone and parathyroid hormone-related protein peptides to adult ovariectomized rats markedly enhances bone mass and biomechanical properties: a comparison of human parathyroid hormone 1-34, parathyroid hormone-related protein 1-36, and SDZ-parathyroid hormone 893.

Daily administration of parathyroid hormone (PTH) and PTH-related protein (PTHrP) peptides has been shown to increase bone mass and strength in animals and, for PTH, to increase bone mass in humans. Long-term direct comparison of multiple members of the PTH/PTHrP family in vivo has not been reported. We therefore selected three PTH/PTHrP molecules for direct comparison in vivo in an adult rat model of postmenopausal osteoporosis: PTH(1-34), PTHrP(1-36), and the PTH analog, SDZ-PTH 893 ¿Leu8, Asp10, Lys11, Ala16, Gln18, Thr33, Ala34 human PTH 1-34 [hPTH(1-34)]¿. A 6-month study was performed in which adult (6-month-old) vehicle-treated ovariectomized (OVX) and sham OVX rats were compared with OVX rats receiving 40 micrograms/kg per day of either PTH(1-34), PTHrP(1-36), or PTH-SDZ-893. Bone mass, as assessed by ash weight and densitometry, bone histomorphometry, biomechanical properties at trabecular and cortical sites, and indices of bone formation markedly increased in all three PTH/PTHrP peptide-treated groups as compared with controls. In general, this improvement followed a rank order of SDZ-PTH-893 > PTH > PTHrP. The adverse effect profile also was greatest with SDZ-PTH-893; these rats developed moderate hypercalcemia, marked renal calcium accumulation, and displayed a 13% mortality. These studies show that PTH(1-34), PTHrP(1-36), and PTH-SDZ-893 significantly and progressively increase bone mass and bone strength in this rat model of postmenopausal osteoporosis. The adverse effect profile correlates in general terms with efficacy. All three peptides show promise as skeletal anabolic agents. Further studies in humans will be required to define optimal efficacy-to-adverse effect ratios and relative efficacy for each peptide in human osteoporosis.

Animals↗
PubMed1997

Intraoperative secretion of intact parathyroid hormone and amino-terminal parathyroid hormone fragments from normal parathyroid glands associated with solitary parathyroid adenoma.

The nonadenomatous parathyroid glands associated with parathyroid adenoma in patients with primary hyperparathyroidism (pHPT) are assumed to exhibit suppressed secretion of parathyroid hormone (PTH). Because the function of these glands is of clinical importance for calcium homeostasis after surgery for pHPT, we studied the decrease of serum levels associated with intact PTH (i-PTH) and amino-terminal PTH (N-PTH) after excision of a parathyroid adenoma. Blood samples were obtained from the cubital vein and the inferior thyroid vein in six patients with pHPT. The results show that the levels of both i-PTH and N-PTH decreased after removal of the parathyroid adenoma (p < 0.05 for both). Because the reduction was more pronounced for i-PTH than for N-PTH, the N/i ratio increased from 0.54 +/- 0.33 to 3.76 +/- 1.62 (p < 0.05). Furthermore, the levels of i-PTH and N-PTH were higher centrally than peripherally both before and after adenoma excision (p < 0.05). The results therefore suggest that the secretion of i-PTH and N-PTH in the remaining normal-size parathyroid glands is not completely suppressed. Furthermore, in these parathyroid glands the secretion of amino-terminal PTH fragments is relatively predominant when compared to the release of the intact PTH. The findings underscore the importance of the N-terminal PTH fragment for maintaining calcium homeostasis during the early postoperative period after surgery for pHPT and may explain the rarity of prolonged hypocalcemia after parathyroidectomy.

Adenoma↗
PubMed1996

Parathyroid hormone content distinguishes true normal parathyroids from parathyroids of patients with primary hyperparathyroidism.

The purpose of this study was to clarify the pathophysiology of primary hyperparathyroidism by looking for differences between parathyroids from eucalcemic patients and patients with primary hyperparathyroidism (HPT) with respect to the following parameters: intracellular parathyroid content of parathyroid hormone (PTH) and parathyroid hormone messenger RNA (PTH mRNA); and serum PTH and calcium levels of patients and patient age. Coded samples of human parathyroid biopsies were assayed for PTH content with a C-terminal-specific radioimmunoassay. Total cellular RNA was extracted, and PTH mRNA was quantified by dot-blot analysis. These results were tabulated along with associated data on patient age, preoperative serum PTH, and preoperative calcium levels. The content of PTH was significantly higher in true normal (TN) parathyroids than in parathyroids from patients with hyperparathyroidism. PTH content of adenomas and hyperplasias were similar. PTH content of normal parathyroids biopsied from patients with parathyroid adenomas (NA) was statistically higher than that of adenomas but statistically lower than that of TN parathyroids. PTH mRNA and PTH content were correlated (p < 0.001) for TN parathyroid glands; however, it was not true for glands (grossly normal or otherwise) in patients with HPT. Patient groups were similar with regard to mean patient age and intracellular PTH mRNA levels. Hypercalcemic patients were similar with regard to preoperative serum calcium and PTH levels. NA parathyroids, adenomas, and hyperplasias are different from TN parathyroids with regard to their PTH content. PTH mRNA was similar across all groups. The relation between intracellular PTH mRNA and PTH was significantly absent in patients with HPT compared with TN glands. Furthermore, we have found that PTH content of normal parathyroid in patients with adenoma is similar to that of hyperplastic and adenoma tissues. These data suggest that the PTH content of parathyroid tissues may be of use in differentiating normal from abnormal parathyroids.

Adenoma↗
PubMed2005

Validation of a method to replace frozen section during parathyroid exploration by using the rapid parathyroid hormone assay on parathyroid aspirates.

HYPOTHESIS: The parathyroid hormone (PTH) content of tissue aspirates is an accurate indicator of parathyroid tissue and can replace frozen section during parathyroid surgery. DESIGN AND SETTINGS: Prospective data collection in a tertiary care hospital with a single surgeon. PATIENTS: One hundred sixty-seven consecutive patients completing limited parathyroid explorations. INTERVENTIONS: Parathyroid adenomas removed during limited parathyroid exploration were aspirated through a 22-gauge needle into 0.5 mL isotonic sodium chloride solution and the solution held on ice in a purple-top tube. Aspirates of in situ thyroid tissue were also taken for comparison. Samples were then assessed to monitor the physiologic impact of the surgery. MAIN OUTCOME MEASUREMENTS: The PTH content of tissue aspirates was compared with histologic identification of removed putative parathyroid tissue. RESULTS: Elevated tissue PTH content was associated with the identification of origin as parathyroid in every case. Tissue aspirates from pathologically proven parathyroid tissue had a mean PTH level of at least 1691 pg/mL, with 160 having values exceeding the upper limit of the assay. This measure was significantly higher than values obtained from thyroid aspirates, which had a mean PTH level of 88 pg/mL (P<.01), reflective of blood levels at the time of aspiration. Using the 99% confidence interval of histologically confirmed parathyroid glands as the lower limit of a positive test result at 1610 pg/mL, tissue aspirate PTH assay has a sensitivity of 97% and a specificity of 100%. CONCLUSIONS: Positive identification of removed tissue as parathyroid is necessary adjunct to limited parathyroid exploration, where decreases in false positive blood PTH levels can be a result of operative manipulation of the neck. Analysis of tissue PTH content during the same assay that is being used for assessing blood PTH concentration is an efficient and accurate method for identifying the tissue with certainty. This measure also prevents the occasional ambiguity in frozen sections of parathyroid tissue that apparently contain thyroidlike colloid material.

Adenoma↗
PubMed1989

Clonal rat parathyroid cell line expresses a parathyroid hormone-related peptide but not parathyroid hormone itself.

A novel parathyroid hormone-related peptide has been identified in tumors associated with the syndrome of humoral hypercalcemia of malignancy. Subsequently, mRNAs encoding this peptide have been found to be expressed in a number of normal tissues, including the parathyroids. Using Northern blotting, RNase protection, and immunochemical techniques, we examined a clonal rat parathyroid cell line originally developed as a model system for studying parathyroid cell physiology. We found that this line expresses the parathyroid hormone-related peptide but not parathyroid hormone itself. Secretion of the parathyroid hormone-related peptide varied inversely with extracellular calcium concentration, but neither calcium nor 1,25-dihydroxyvitamin D3 appeared to influence steady-state parathyroid hormone-related peptide mRNA levels. This clonal line may prove to be an interesting system for studying the factors responsible for tissue-specific parathyroid hormone and parathyroid hormone-related peptide gene expression.

Animals↗
PubMed1996

The expression of parathyroid hormone and parathyroid hormone-related protein in developing rat parathyroid glands.

Secretion of parathyroid hormone-related protein (PTHrP) by sheep fetal parathyroid glands is reported to be an important factor in the maintenance of a placental calcium pump. The aim of the present study was to determine whether the developing rat parathyroid glands express PTHrP or parathyroid hormone (PTH), or both. Hybridisation histochemistry was used to detect transcription of PTHrP and PTH in serial paraffin sections through the 12.5- and 13.5-day rat embryo parathyroid anlage, as well as in sections through the 17.5-day embryonic and adult parathyroid glands. Results show strong expression of PTH in the 13.5-day embryonic parathyroid anlage, as well as in the parathyroid gland of the 17.5-day embryo and adult. Transcription of the PTHrP gene was not detected. The more sensitive technique of reverse transcription PCR was then performed. The pharyngeal region of 11.5-, 12.5- and 13.5-day rat embryos was dissected out and, at each stage, RNA was extracted from these tissues, as well as pooled tissues from the rest of the embryo. RNA that had been extracted from adult thyroid/parathyroid tissue was also tested. After reverse transcription, the resulting cDNAs were amplified by PCR (50 cycles) using specific PTH and PTHrP primers. The results show an abundance of PTH mRNA, specific to the pharyngeal region of the 13.5-day embryo, as well as to adult thyroid/parathyroid tissue. PTHrP expression was detected at very low levels in both parathyroid and extraparathyroid tissues. The presence of immunoreactive PTHrP and immunoreactive PTH in the pharyngeal region and rest of the body of 12.5- and 13.5-day rat embryos was assessed by specific RIAs. Whilst immunoreactive PTHrP was not detected in any of the tissues assayed, immunoreactive PTH was detected only in the pharyngeal region of the 13.5-day embryo. This confirms the results obtained from the gene expression studies. We conclude then that, in the developing rat embryo, PTH rather than PTHrP is more likely to play a role in calcium regulation. This is in contrast with the reported situation in the sheep, and suggests that fundamental species differences in fetal calcium regulation exist in mammals.

Aging↗
PubMed1977

The effect of 1,25-dihydroxycholecalciferol on the parathyroid hormone secretion of porcine parathyroid glands and human parathyroid adenomas in vitro.

The effect of 1,25-dihydroxycholecalciferol (1,25-(OH)2-D3) on parathyroid hormone secretion by porcine parathyroid glands and human parathyroid adenoma tissue was investigated by in vitro incubation. The addition of 100 nmoles 1,25-(OH)2-D3 to the medium inhibited significantly the release of immunoreactive parathyroid hormone by 63--65%. This suppression was reversible when 1,25-(OH)2-D3 was removed again. The inhibition of parathyroid hormone release observed in human parathyroid adenoma tissue was similar to that in normal porcine parathyroid glands. This indicates that adenoma tissue is sensitive to regulatory influences. As well as calcium, 1,25-(OH)2-D3 may act as another feedback inhibitor of parathyroid hormone secretion.

Adenoma↗
PubMed1999

Hyperphosphatemia accelerates parathyroid cell proliferation and parathyroid hormone secretion in severe secondary parathyroid hyperplasia.

We studied the role of phosphorus retention in parathyroid cell proliferation and parathyroid hormone (PTH) oversecretion in severe secondary parathyroid hyperplasia. Mice transplanted with human parathyroid tissue from a patient who had undergone parathyroidectomy for severe secondary hyperparathyroidism were divided into four groups; each group was given a diet with a different phosphorus content (0.4, 0.7, 1.0, and 1.2%) to alter serum phosphorus concentrations. Histologic examinations of grafts by hematoxylin-eosin or by bromodeoxyuridine (BrdU) immunohistochemical staining were performed to assess parathyroid cell proliferation. Changes in serum phosphorus concentrations unidirectionally affected PTH secretion from the graft, because human PTH did not cross-react with mouse PTH. Serum phosphorus concentrations of 1.0P and 1.2P groups were significantly higher than those of 0.4P and 0.7P groups (p<0.05). Serum phosphorus concentrations were significantly correlated with the gradient of human PTH elevation with a coefficient of 0.48 and a p<0.05. Furthermore, serum phosphorus concentrations and the gradient of human PTH elevation were significantly higher in mice with BrdU-immunoreactive cells in the parathyroid graft than in mice without immunoreactive cells in the graft. These results indicate that uncontrolled hyperphosphatemia may accelerate the proliferation of parathyroid cells, exacerbating PTH oversecretion.

Animals↗
PubMed1983

Immunoperoxidase study of uncommon parathyroid tumors. Report of two cases of nonfunctioning parathyroid carcinoma and one intrathyroid parathyroid tumor-producing amyloid.

Nonfunctioning carcinomas of the parathyroid gland are rare and difficult to diagnose. They are often confused with thyroid tumors or with metastasis from other sites. We report two cases of nonfunctioning parathyroid carcinomas; one was originally diagnosed as follicular carcinoma of the thyroid gland. The immunohistochemical demonstration of parathormone in the tumor cells established the parathyroid origin of these neoplasms. An intrathyroid parathyroid tumor, associated with large amounts of interstitial amyloid, mimicking medullary carcinoma of the thyroid, in a patient with primary hyperparathyroidism is also reported. Positive immunoreaction in the tumor cells for parathormone, negative staining for calcitonin, and the return of patients' serum calcium levels to normal after tumor resection, confirmed the parathyroid nature of this neoplasm. Immunohistochemistry studies proved to be extremely helpful in establishing the diagnoses of these unusual parathyroid tumors.

Adult↗
PubMed1999

Proliferation of parathyroid cells negatively correlates with expression of parathyroid hormone-related protein in secondary parathyroid hyperplasia.

BACKGROUND: Parathyroid hormone-related protein (PTHrP) is now suspected to act as an autocrine or paracrine regulator of cell growth or differentiation, although it was originally reported as a hypercalcemic substance in malignancies. This study was performed to assess the relationship between PTHrP expression and cell proliferation in human parathyroid glands. METHODS: The localization of PTH and PTHrP was studied in 42 samples of hyperplastic parathyroid from 14 long-term hemodialysis cases with immunohistochemistry and in situ hybridization. Results were compared with proliferative activity (proliferating cell nuclear antigen index: counts of proliferating cell nuclear antigen-positive cells/100 cells). The localization of the PTH/PTHrP receptor was also examined. Ten normal glands were studied as controls. RESULTS: In hyperplasia, cells positive for PTH, PTHrP, or both were observed immunohistochemically. The areas expressing PTHrP mRNA completely coincided with those positive for PTHrP immunohistochemically. Oxyphilic or transitional oxyphilic cells were consistently positive for PTHrP. PTH/PTHrP receptors were located in the cytoplasmic membrane in most parathyroid cells. Proliferating cell nuclear antigen-positive cells were rare in normal glands with an index of 0. 22 +/- 0.09 (mean +/- sem). They were significantly increased in hyperplastic cases but less for PTHrP-positive than for -negative cells (1.25 +/- 0.16 as compared with 7.80 +/- 0.52; P < 0.0001). CONCLUSION: The observed low level of proliferation of PTHrP-positive cells suggests a functional role for PTHrP as a possible growth suppressor in the human parathyroid.

Adult↗
PubMed1985

Co-existent parathyroid adenoma and thyroid carcinoma. Nonspecificity of dual tracer parathyroid imaging for parathyroid lesions.

Dual tracer parathyroid imaging (DTPI) using Tc-99m and TI-201 has a reported sensitivity of 92% for the detection of parathyroid adenomas. A patient with biopsy-proven parathyroid adenoma as well as papillary thyroid carcinoma is presented. To date, this is the first such case ever to be reported and implies that DTPI, although a sensitive diagnostic modality for parathyroid adenoma detection, is not specific. The diagnosis of primary hyperparathyroidism has recently been established more frequently than in the past due to detection of elevated serum calcium levels on routine blood samples, relatively sensitive parathormone (PTH) assays, and noninvasive imaging modalities such as nuclear medicine, CT scanning, and ultrasonography. At our institution, we have successfully detected the location of parathyroid adenomas in many cases, using the dual tracer method with TI-201 and Tc-99m, confirmed at surgery. We present a case of primary hyperparathyroidism in which two distinct lesions were detected by nuclear imaging: one lesion was proven at surgery to be a parathyroid adenoma, while the other represented thyroid carcinoma.

Adenoma↗
PubMed1993

Parathyroid hormone-like peptide and parathyroid hormone are secreted from bovine parathyroid via different pathways.

Parathyroid hormone-like peptide is a recently discovered protein which is thought to be responsible for the hypercalcemia of malignancy. Through the use of radioimmunoassay, Northern analysis and Western blot techniques this protein has been demonstrated to occur in a variety of tumor and normal cells. Its role in normal physiology is not established nor is there knowledge regarding its synthesis, secretion, and storage. We have investigated characteristics of the secretion of parathyroid hormone-like peptide in bovine parathyroid gland slices and cells to learn whether or not this protein is secreted in a manner similar to that of parathyroid hormone. We have used radioimmunoassays specific for PTH and PTH-rP to measure the secretion of each protein and have found that, unlike PTH, PTH-rP secretion was not influenced by the medium calcium concentration. Similarly, PTH-rP secretion was not influenced by other known PTH secretagogues such as c-AMP or isoproterenol. An examination of the subcellular distribution of PTH-rP revealed that 75-90% of it occurs in the soluble fraction of cell lysates. Analysis of isolated secretory granules demonstrated the presence of PTH while PTH-rP was undetectable in these organelles. We conclude that PTH-rP is not secreted from parathyroid cells via the regulated pathway utilizing PTH secretory granules.

Animals↗
PubMed1989

Bovine parathyroid tissue: a model to compare the biosynthesis and secretion of parathyroid hormone and parathyroid hormone-related peptide.

Bovine parathyroid tissue was evaluated as a model to compare parathyroid hormone-related peptide (PTH-rP) and parathyroid hormone (PTH) secretion. Tissue was incubated in variable calcium levels (n = 5). A parathyroid cell digest was prepared from collagenase-treated glands. PTH-rP and PTH levels were determined by radioimmunoassay. PTH-rP bioactivity was determined by 3H-cAMP production in a UMR 106 cell bioassay. PTH-rP levels in the incubation medium were 2.0 ng/mg protein (0.25 mmol Ca++), 2.2 ng/mg protein (1.25 mmol Ca++), and 1.9 ng/mg protein (2.5 mmol/L Ca++). PTH levels were 321 ng/mg protein (0.25 mmol/L Ca++) and 200 ng/mg protein (2.5 mmol Ca++). Therefore, calcium significantly inhibited PTH but not PTH-rP secretion (p = 0.03). Addition of incubation medium to the bioassay resulted in 3H-cAMP levels that were 8 to 10 times greater than basal levels. Greater than 50% of the activity persisted after addition of PTH antibody, demonstrating that a significant amount of the activity was caused by PTH-rP. Tissue PTH-rP was 5.1 ng/mg protein, compared with 2080 ng/mg protein for PTH. We conclude that (1) bovine parathyroid tissue contains bioactive PTH-rP and is a useful model to compare the biosynthesis and secretion of PTH-rP and PTH in normal tissue and (2) unlike PTH, PTH-rP secretion is not regulated by calcium.

Animals↗
PubMed1986

Parathyroid cell surface autoantibodies that inhibit parathyroid hormone secretion from dispersed human parathyroid cells.

Serum autoantibodies directed toward antigenic determinants on the surface of human parathyroid cells (PTAb-CS) have been demonstrated in a subset (8 of 23) of adult patients with idiopathic hypoparathyroidism (IHP). In sera from 3 of 8 patients with PTAb-CS, binding of these autoantibodies to their respective parathyroid cell surface antigen(s) resulted in marked inhibition of parathyroid hormone (PTH) secretion in an in vitro dispersed human parathyroid cell (dPTC) system. In 1 subject evaluated longitudinally, circulating levels of PTAb-CS, and the magnitude of the inhibitory effect on PTH secretion, temporally correlated with the clinical course of the hypoparathyroidism. These findings suggest a causative role for antibodies directed against cell surface antigens in parathyroid dysfunction in some cases of "autoimmune" hypoparathyroidism.

Aged↗
PubMed1995

DNA index and ploidy distinguish normal human parathyroids from parathyroid adenomas and primary hyperplastic parathyroids.

BACKGROUND: The goal of this study was to identify factors that might aid in diagnosis and intraoperative management of hyperparathyroidism. METHODS: We analyzed biopsy specimens of 242 parathyroids from 159 patients by use of flow cytometry and image cytometry (ICM) for DNA index (DI), defined as the content of nuclear DNA compared with that expected for a DNA diploid standard, for proliferative index (PI), and for ploidy (diploid versus aneuploid or tetraploid). RESULTS: True normal and normal parathyroids from patients with solitary adenomas were uniformly diploid. Abnormal ploidy (aneuploidy or tetraploidy) was identified frequently in adenomas and occasionally in hyperplasias with the exception that multiple endocrine neoplasia (MEN) biopsy specimens were uniformly diploid. DI for adenomas was similar to that for hyperplasias, and DI of both was higher than for normal glands. ICM-DI correlated positively with flow cytometry-DI and patient age and inversely with serum parathyroid hormone. PI was relatively low in all groups but was higher for hyperplasias versus normal parathyroids from patients with solitary adenomas and MEN versus non-MEN. PI correlated inversely with patient age. CONCLUSIONS: DI by ICM differentiates normal from abnormal parathyroids. DI might influence extent of resection in two- and three-gland hyperplasia and selection of the most appropriate gland for autografting and cryopreservation in patients with four-gland hyperplasia.

Adenoma↗
PubMed1986

Identification of parathyroid hormone messenger ribonucleic acid in an apparently nonfunctioning parathyroid carcinoma transformed from a parathyroid carcinoma with hyperparathyroidism.

mRNA coding for pre-pro-PTH, a precursor of PTH, was sought in an apparently nonfunctioning parathyroid carcinoma that had transformed from one that was previously functioning. Total poly(A+) RNA was prepared by phenol-chloroform-isoamyl alcohol extraction and oligo-dT-cellulose affinity chromatography from the tumor tissue and bovine parathyroid glands. In the rabbit reticulocyte lysate cell-free translation system, total poly(A+) RNA from the tumor as well as that from bovine parathyroid glands directed the translation of a product which was specifically precipitated by an anti-PTH serum and which migrated at the same position as pre-pro-PTH on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These results indicated the presence of mRNA coding for pre-pro-PTH (PTH mRNA) in an apparently nonfunctioning parathyroid carcinoma, suggesting that PTH synthesis is not always absent in parathyroid carcinomas which are not accompanied by hyperparathyroidism.

Animals↗
PubMed2003

Parathyroid hormone (PTH) secretion, PTH mRNA and calcium-sensing receptor mRNA expression in equine parathyroid cells, and effects of interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha on equine parathyroid cell function.

Parathyroid hormone (PTH) is secreted by the chief cells of the parathyroid gland in response to changes in ionized calcium (Ca(2+)) concentrations. In this study, we measured PTH secretion, and PTH mRNA and calcium-sensing receptor (CaR) mRNA expression by equine parathyroid chief cells in vitro. We also evaluated the effects of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha on PTH secretion, and PTH and CaR mRNA expression. The relationship between PTH and Ca(2+) was inversely related. PTH secretion decreased from 100% (day 0) to 13% (day 30). PTH mRNA expression declined from 100% (day 0) to 25% (day 30). CaR mRNA decreased from 100% (day 0) to 16% (day 30). Chief cells exposed to high (2.0 mM) Ca(2+) concentrations had a lower PTH mRNA expression compared with low Ca(2+) concentrations. Ca(2+) concentrations had no effect on CaR mRNA expression. The inhibitory effect of high Ca(2+) concentrations on PTH secretion also declined over time. After day 10, there was no significant difference in PTH secretion between low and high Ca(2+ )concentrations. IL-1beta decreased both PTH secretion (75%) and PTH mRNA expression (73%), and resulted in a significant overexpression of CaR mRNA (up to 142%). The effects of IL-1beta were blocked by an IL-1 receptor antagonist. IL-1beta decreased the Ca(2+) set-point from 1.4 mM to 1.2 mM. IL-6 decreased PTH secretion (74%), but had no effect on PTH and CaR mRNA expression. TNF-alpha had no effect on PTH secretion, and PTH and CaR mRNA expression. In summary, the decreased responsiveness of parathyroid cells to Ca(2+) from 0 to 30 days can be explained, in part, by the reduced CaR expression. IL-1beta and IL-6 but not TNF-alpha affected parathyroid function in vitro and may be important in influencing PTH secretion in the septic horse.

Animals↗