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1

Parathyroid Hormone, Calcitonin, and Vitamin D  

NASA Technical Reports Server (NTRS)

Analyses of secretion of parathyroid hormone during tests of stimulation and suppression of hormone-secretory activity using infusions of EDTA and calcium, respectively, have established that, in contrast to previous views, secretion of the hormone is not autonomous in many patients that have adenomatous hyperparathyroidism, but is responsive to changes in blood-calcium concentration. These findings have led to a new understanding of the pathophysiology of hormone production in hyperparathy-roidism. A related application of the diagnostic use of the radioimmunoassay is the preoperative localization of parathyroid tumors and the distinction between adenomas and chief-cell hyperplasia. Work involving catheterization and radioimmunoassay of blood samples obtained from the subclavin and innominate veins and the venae cavae, led to localization in a high percentage of patients. However, this procedure has been adopted recently to detect hormone concentration in the small veins directly draining the parathyroid glands.

Potts, J. T.

1972-01-01

2

Vitamin D metabolites and bioactive parathyroid hormone levels during Spacelab 2  

NASA Technical Reports Server (NTRS)

The effect of an 8-day space flight (Spacelab mission 2) on plasma levels of the vitamin D and parathyroid hormones is investigated experimentally in four crew members. The results are presented in tables and graphs and briefly characterized. Parathyroid hormone levels remained normal throughout the flight, whereas vitamin D hormone levels increased significantly on day 1 but returned to normal by day 7.

Morey-Holton, Emily R.; Schnoes, Heinrich K.; Deluca, Hector F.; Phelps, Mary E.; Klein, Robert F.

1988-01-01

3

Vitamin D, parathyroid hormone and muscle impairment in myotonic dystrophies.  

PubMed

Parathyroid function in Myotonic Dystrophy (DM) patients has been poorly investigated. Parathyroid and muscle parameters were assessed in 31 male DM1 (44±2 years), 13 male DM2 (56±2 years) and 32 healthy controls. Hyperparathyroidism was diagnosed in 18% of patients without differences between DM types. In all DM patients, hyperparathyroidism was associated with normocalcemia but one with hypercalcemia. DM patients presented significantly higher PTH and lower vitamin D (25OHD) compared with controls, also considering seasonality. Severe vitamin D deficiency (25OHD<10 ng/ml) was diagnosed in 40% and hypovitaminosis D (25OHD<30 ng/ml) occurred in 88% of DM patients. About one-third of DM1 presented hypophosphatemia associated with elevated PTH levels. Serum 25OHD levels negatively correlated with PTH and with body fat mass. Considering DM1 patients, serum PTH levels positively correlated with CTG triplet repeats. Furthermore, PTH levels negatively correlated with total modified Medical Research Council (MRC) and positively with Muscular Impairment Rating Scale (MIRS). By contrast, in DM2 patients muscle assessment did not show any correlation with parathyroid function. In conclusion, we arrived at the following: 1) severe vitamin D deficiency is common in DM patients and it is associated with secondary hyperparathyroidism; 2) primary hyperparathyroidism, though rare, may occur; 3) increased adiposity in DM may be a risk factor for hypovitaminosis D; and 4) high serum PTH levels may indicate a muscle impairment, at least in DM1. PMID:23809192

Passeri, E; Bugiardini, E; Sansone, V A; Valaperta, R; Costa, E; Ambrosi, B; Meola, G; Corbetta, S

2013-08-15

4

Parathyroid hormone, calcitonin, and vitamin D 1974: Present status of physiological studies and analysis of calcium homeostasis  

NASA Technical Reports Server (NTRS)

The role of parathyroid hormone, calcitonin, and vitamin D in the control of calcium and bone metabolism was studied. Particular emphasis was placed on the physiological adaptation to weightlessness and, as a potential model for this purpose, on the immobilization characteristic of space flight or prolonged bed rest. The biosynthesis, control of secretion, and metabolism of these hormonal agents is considered.

Potts, J. T., Jr.; Swenson, K. G.

1975-01-01

5

Regulation by vitamin D metabolites of parathyroid hormone gene transcription in vivo in the rat.  

PubMed Central

In vitro 1,25-dihydroxycholecalciferol (1,25(OH)2D3) decreased levels of preproparathyroid(preproPTH) hormone mRNA. We have now pursued these studies in vivo in the rat. Rats were administered vitamin D metabolites i.p. and the levels of preproPTH mRNA were determined in excised parathyroid-thyroid glands by blot hybridization. PreproPTH mRNA levels were less than 4% of basal at 48 h after 100 pmol 1,25(OH)2D3, with no increase in serum calcium. Gel blots showed that 1,25(OH)2D3 decreased preproPTH mRNA levels without any change in its size (833 basepair). Microdissected parathyroids after 1,25(OH)2D3 (100 pmol) showed mRNA levels for preproPTH were 40 +/- 8% of controls, but for beta-actin were 100% of controls. The relative potencies of vitamin D metabolites were: 1,25(OH)2D3 greater than 24,25(OH)2D3 greater than 25(OH)D3 greater than vitamin D3. In vitro nuclear transcription showed that 1,25(OH)2D3-treated (100 pmol) rats' PTH transcription was 10% of control, while beta-actin was 100%. These results show that 1,25(OH)2D3 regulates PTH gene transcription. PTH stimulates 1,25(OH)2D3 synthesis, which then inhibits PTH synthesis, thus completing an endocrinological feedback loop. Images PMID:3771798

Silver, J; Naveh-Many, T; Mayer, H; Schmelzer, H J; Popovtzer, M M

1986-01-01

6

Dietary vitamin D intake is not associated with 25-hydroxyvitamin D3 or parathyroid hormone in elderly subjects, whereas the calcium-to-phosphate ratio affects parathyroid hormone.  

PubMed

This cross-sectional study investigates whether serum 25-hydroxyvitamin D3 [25(OH)D3] and intact parathyroid hormone (iPTH) are affected by vitamin D, calcium, or phosphate intake in 140 independently living elderly subjects from Germany (99 women and 41 men; age, 66-96 years). We hypothesized that habitual dietary intakes of vitamin D, calcium, and phosphate are not associated with 25(OH)D3 or iPTH and that body mass index confounds these associations. Serum 25(OH)D3 and iPTH were measured by an electrochemiluminescence immunoassay. Dietary intake was determined using a 3-day estimated dietary record. The median dietary intake levels of vitamin D, calcium, and phosphate were 3 ?g/d, 999 mg/d, and 1250 mg/d, respectively. Multiple regression analyses confirmed that dietary vitamin D and calcium did not affect 25(OH)D3 or iPTH; however, supplemental intakes of vitamin D and calcium were associated with 25(OH)D3 after adjustment for age, sex, body composition, sun exposure, physical activity, and smoking. In addition, phosphate intake and the calcium-to-phosphate ratio were associated with iPTH after multiple adjustments. In a subgroup analysis, calcium and vitamin D supplements, as well as phosphate intake, were associated with 25(OH)D3 and/or iPTH in normal-weight subjects only. Our results indicate that habitual dietary vitamin D and calcium intakes have no independent effects on 25(OH)D3 or iPTH in elderly subjects without vitamin D deficiency, whereas phosphate intake and the calcium-to-phosphate ratio affect iPTH. However, vitamin D and calcium supplements may increase 25(OH)D3 and decrease iPTH, even during the summer, but the impact of supplements may depend on body mass index. PMID:23890356

Jungert, Alexandra; Neuhäuser-Berthold, Monika

2013-08-01

7

Correlation of bone histology with parathyroid hormone, vitamin D3, and radiology in end-stage renal disease  

Microsoft Academic Search

Correlation of bone histology with parathyroid hormone, vitamin D3, and radiology in end-stage renal disease. We analyzed transiliac bone biopsy specimens from 30 end-stage renal failure patients, taken at the time of admission for CAPD training. Results were compared with values of iPTH, bone alkaline phosphatase, 1,25-dihydroxyvitamin D3, skeletal survey, quantitative computed tomography (QCT) and single photon absorptiometry (SPA) bone

Alastair J Hutchison; Rick W Whitehouse; Helen F Boulton; Judy E Adams; E Barbara Mawer; Tony J Freemont; Ram Gokal

1993-01-01

8

Effects of gastric bypass procedures on bone mineral density, calcium, parathyroid hormone, and vitamin D.  

PubMed

Weight loss after gastric bypass procedures has been well studied, but the long-term metabolic sequelae are not known. Data on bone mineral density (BMD), calcium, parathyroid hormone, and vitamin D were collected preoperatively and at yearly intervals after gastric bypass procedures. A total of 230 patients underwent preoperative BMD scans. Fifteen patients were osteopenic preoperatively, and three patients subsequently developed osteopenia postoperatively within the first year. No patient had or developed osteoporosis. At 1 year, total forearm BMD decreased by 0.55% (n = 91; P = .03) and radius BMD had increased overall by 1.85% (n = 23; P = .008); both total hip and lumbar spine BMD decreased by 9.27% (n = 22; P < .001) and 4.53% (n = 31; P < .001), respectively. By the second postoperative year, BMD in the total forearm had decreased an additional 3.62% (n = 14; P < .001), whereas radius BMD remained unchanged. Although total hip and lumbar spine BMD significantly decreased at 1 year, by year 2 both total hip and lumbar spine BMD only slightly decreased and were not significantly different from before the operation. Serum calcium decreased from 9.8 mg/dL to 9.2 during the first year (not significant [NS]) and then to 8.8 (NS) by the second year. Parathyroid hormone increased from 59.7 pg/mL (nl 10-65 pg/mL) preoperatively to 63.1 during year 1 (NS) and continued to increase to 64.7 by year 2 (NS). No difference was noted among levels of 25-hydroxy vitamin D preoperatively (25.2 ng/mL; nl 10-65 ng/mL), at 1 year (34.4), and at 2 years (35.4). Our data indicate that bone loss is highest in the first year after gastric bypass with stabilization, and that, in some cases, there is an increase in bone density after the first year. PMID:16269381

Johnson, Jason M; Maher, James W; Samuel, Isaac; Heitshusen, Deborah; Doherty, Cornelius; Downs, Robert W

2005-11-01

9

Regulation of parathyroid hormone gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat.  

PubMed Central

In vivo in the rat 1,25(OH)2D3 decreases and a low calcium increases PTH mRNA levels. We now report the effect of 3 and 8 wk of changes in dietary vitamin D and calcium on PTH mRNA levels. PTH mRNA levels were increased by 3 wk of calcium deficiency (five times), a vitamin D-deficient diet (two times), and combined deficiency (10 times), but not changed by high calcium. Vitamin D-deficient-diet rats' PTH mRNA did not decrease after a single large dose of 1,25(OH)2D3, but did decrease partially after repeated daily doses of 1,25(OH)2D3. Rats after a vitamin D-, calcium-deficient (-D-Ca) diet did not respond to changes in serum calcium at 1 h. Flow cytometry of isolated cells from parathyroid-thyroid tissue separated the smaller parathyroid from the larger thyroid cells and allowed an analysis of parathyroid cell number. In normal vitamin D/normal calcium (NDNCa) rats the parathyroid cells were 24.7 +/- 3.4% (n = 6) of the total cell number, whereas in -D-Ca rats they were 41.8 +/- 6.6% (n = 6) (P less than 0.05). That is, -D-Ca rats had 1.7 times the number of cells, whereas they had 10 times the amount of PTH mRNA, indicating the major contribution (6 times) of increased PTH gene expression per cell. Moreover, a calcium-deficient, more so than a vitamin D-deficient diet, amplifies the expression of the PTH gene, and vitamin D is necessary for an intact response of PTH mRNA to 1,25(OH)2D3 or calcium. Images PMID:2212016

Naveh-Many, T; Silver, J

1990-01-01

10

Regulation by vitamin D metabolites of messenger ribonucleic acid for preproparathyroid hormone in isolated bovine parathyroid cells.  

PubMed Central

We have recently determined that high calcium concentrations, in parallel with their suppressive effects on parathyroid hormone (PTH) secretion, reversibly and specifically decrease preproPTH mRNA in cultured bovine parathyroid cells. In order to determine whether vitamin D metabolites also regulate the content of preproPTH mRNA, we tested their effects on bovine parathyroid cells in the same culture system. Levels of preproPTH mRNA were determined by dot-blot hybridization or blot hybridization with a labeled cloned cDNA probe. Incubation with 1,25-dihydroxycholecalciferol at doses varying from 10 pM to 0.1 microM caused a direct decrease in mRNA down to 50% of control values at 48 hr. There was no evidence that 1,25-dihydroxycholecalciferol, even at the highest concentrations, had any toxic effects on cell number or viability or on total RNA or RNA synthesis. Levels of alpha-actin mRNA did not change in the same experiments, and the suppression of preproPTH mRNA was reversible. When the relative potency of various vitamin D metabolites in suppressing preproPTH mRNA was evaluated, 1,25-dihydroxycholecalciferol greater than 24,25-dihydroxycholecalciferol greater than 25-hydroxycholecalciferol greater than vitamin D3 (cholecalciferol). These effects were highly specific and suggest that vitamin D metabolites play an important role in regulating the production of PTH. Images PMID:3858880

Silver, J; Russell, J; Sherwood, L M

1985-01-01

11

Prospective associations of vitamin D status with ?-cell function, insulin sensitivity, and glycemia: the impact of parathyroid hormone status.  

PubMed

Previous studies have yielded conflicting findings on the relationship between low vitamin D (25-OH-D) and impaired glucose homeostasis. In this context, we hypothesized that combined assessment of 25-OH-D with its regulator parathyroid hormone (PTH) may be required for optimal evaluation of the impact of vitamin D status on glucose metabolism. Thus, we evaluated the prospective associations of 25-OH-D and PTH at 3 months postpartum with ?-cell function (Insulin Secretion-Sensitivity Index-2 [ISSI-2]), insulin sensitivity (Matsuda index), and glycemia at 12 months postpartum in 494 women undergoing serial metabolic characterization. Notably, 32% of those with prediabetes/diabetes mellitus at 12 months postpartum had both vitamin D deficiency and PTH in the highest tertile at 3 months postpartum. On multiple-adjusted linear regression analyses, vitamin D deficiency/insufficiency with PTH in the highest tertile at 3 months independently predicted poorer ?-cell function (P = 0.03) and insulin sensitivity (P = 0.01) and increased fasting (P = 0.03) and 2-h glucose (P = 0.002) at 12 months postpartum. In contrast, vitamin D deficiency/insufficiency with lower PTH did not predict these outcomes. In conclusion, only vitamin D deficiency/insufficiency with increased PTH is an independent predictor of ?-cell dysfunction, insulin resistance, and glycemia, highlighting the need for consideration of the PTH/25-OH-D axis when studying the impact of vitamin D status on glucose homeostasis. PMID:24875346

Kramer, Caroline K; Swaminathan, Balakumar; Hanley, Anthony J; Connelly, Philip W; Sermer, Mathew; Zinman, Bernard; Retnakaran, Ravi

2014-11-01

12

Vitamin D3 decreases parathyroid hormone in HIV-infected youth being treated with tenofovir: a randomized, placebo-controlled trial  

Technology Transfer Automated Retrieval System (TEKTRAN)

Objective: To determine the effect of vitamin D (VITD) supplementation on tubular reabsorption of phosphate (TRP), serum parathyroid hormone (PTH), bone alkaline phosphatase (BAP), and C telopeptide (CTX) in HIV-infected youth receiving and not receiving tenofovir-containing cART (TDF). Design: Ra...

13

Aluminum, parathyroid hormone, and osteomalacia  

SciTech Connect

Aluminum exposure in man is unavoidable. The occurrence of dialysis dementia, vitamin D-resistant osteomalacia, and hypochromic microcytic anemia in dialysis patients underscores the potential for aluminum toxicity. Although exposure via dialysate and hyperalimentation leads to significant tissue aluminum accumulation, the ubiquitous occurrence of aluminum and the severe pathology associated with large aluminum burdens suggest that smaller exposures via the gastrointestinal tract and lungs could represent an important, though largely unrecognized, public health problem. It is clear that some aluminum absorption occurs with the ingestion of small amounts of aluminum in the diet and medicines, and even greater aluminum absorption is seen in individuals consuming large amounts of aluminum present in antacids. Aluminum absorption is enhanced in the presence of elevated circulating parathyroid hormone. In addition, elevated PTH leads to the preferential deposition of aluminum in brain and bone. Consequently, PTH is likely to be involved in the pathogenesis of toxicities in those organs. PTH excess also seems to lead to the deposition of aluminum in the parathyroid gland. The in vitro demonstration that aluminum inhibits parathyroid hormone release is consistent with the findings of a euparathyroid state in dialysis patients with aluminum related vitamin D-resistant osteomalacia. Nevertheless, it seems likely that hyperparathyroidism is at least initially involved in the pathogenesis of aluminum neurotoxicity and osteomalacia; the increases in tissue aluminum stores are followed by suppression of parathyroid hormone release, which is required for the evolution of osteomalacia. Impaired renal function is not a prerequisite for increased tissue aluminum burdens, nor for aluminum-related organ toxicity. Consequently, it is likely that these diseases will be observed in populations other than those with chronic renal disease.

Burnatowska-Hledin, M.A.; Kaiser, L.; Mayor, G.H.

1983-01-01

14

A case report: Giant cystic parathyroid adenoma presenting with parathyroid crisis after Vitamin D replacement  

PubMed Central

Background Parathyroid adenoma with cystic degeneration is a rare cause of primary hyperparathyroidism. The clinical and biochemical presentation may mimic parathyroid carcinoma. Case presentation We report the case of a 55?year old lady, who had longstanding history of depression and acid peptic disease. Serum calcium eight months prior to presentation was slightly high, but she was never worked up. She was found to be Vitamin D deficient while being investigated for generalized body aches. A month after she was replaced with Vitamin D, she presented to us with parathyroid crisis. Her corrected serum calcium was 23.0?mg/dL. She had severe gastrointestinal symptoms and acute kidney injury. She had unexplained consistent hypokalemia until surgery. Neck ultrasound and CT scan revealed giant parathyroid cyst extending into the mediastinum. After initial medical management for parathyroid crisis, parathyroid cystic adenoma was surgically excised. Her serum calcium, intact parathyroid hormone, creatinine and potassium levels normalized after surgery. Conclusion This case of parathyroid crisis, with very high serum calcium and parathyroid hormone levels, is a rare presentation of parathyroid adenoma with cystic degeneration. This case also highlights that Vitamin D replacement may unmask subclinical hyperparathyroidism. Consistent hypokalemia until surgery merits research into its association with hypercalcemia. PMID:22840059

2012-01-01

15

Arterial Structure and Function in Mild Primary Hyperparathyroidism Is Not Directly Related to Parathyroid Hormone, Calcium, or Vitamin D  

PubMed Central

Objective Elevated levels of calcium and parathyroid hormone (PTH), characteristics of primary hyperparathyroidism (PHPT), may be associated with cardiovascular morbidity and mortality in the general population. We evaluated the possible vascular effects of these risk factors in patients with mild PHPT by using standard methods and new imaging techniques. Design A prospective case-control study. Subjects and Methods Forty-eight patients with mild PHPT without any known cardiovascular risk factors were studied at baseline and at one year after parathyroidectomy (PTX) in comparison with 48 healthy age- and gender-matched controls. We measured biochemical variables, augmentation index (AIx), aortic pulse wave velocity (PWVao), radial (IMTrad) and common carotid artery (IMTcca) intima media thicknesses, and the grayscale median (IM-GSM) of the latter. Results No significant differences were observed between PHPT patients and controls at baseline for AIx (28.6±12.2 vs. 27.7±12.8%), IMTrad (0.271±0.060 vs. 0.255±0.053 mm), IMTcca (0.688±0.113 vs. 0.680±0.135 mm), or IM-GSM (82.3±17.2 vs. 86.5±15.3), while PWVao was slightly higher in patients (8.68±1.50 vs. 8.13±1.55, p<0.05). Systolic blood pressure (SBP), calcium, and PTH were higher in patients compared with controls, and decreased after PTX, while vitamin D was lower in patients and increased after PTX. While AIx, PWVao, IMTrad, and IMTcca were related to SBP, neither correlated to vitamin D levels. Only PWVao correlated weakly to plasma PTH (r?=?0.29, p<0.01) and ionized calcium (r?=?0.22, p<0.05) but showed no relation when age and SBP were adjusted for. Conclusion We found normal arterial function despite high calcium, PTH, and low vitamin D levels, in patients with mild PHPT without cardiovascular risk factors. The cardiovascular risk associated with low vitamin D and/or high PTH and calcium levels may be explained by their coupling to blood pressure and other risk factors rather than direct effects on arterial structure. PMID:22815708

Ring, Margareta; Farahnak, Parastou; Gustavsson, Tomas; Nilsson, Inga-Lena; Eriksson, Maria J.; Caidahl, Kenneth

2012-01-01

16

Effects of vitamin D on parathyroid hormone and clinical outcomes in peritoneal dialysis: a narrative review.  

PubMed

Vitamin D deficiency is very prevalent in dialysis and peritoneal dialysis (PD) patients show lower levels of cholecalciferol (25(OH)D3) than hemodialysis patients. We conducted a systematic narrative review to assess the effects of vitamin D therapy on control of secondary hyperparathyroidism and clinical outcomes induced by vitamin D pleiotropic effects. Medline database was searched for cohort and intervention studies reporting data on vitamin D (all sterols including synthetic analogs) and peritoneal dialysis without language restriction. Two authors independently extracted data. Twenty-nine observational and eleven interventional studies were identified for inclusion (1,036 subjects). PTH levels decreased in twenty-nine studies, increased in one study and remained stable in ten studies. Thirty-three studies analyzed the oral route for vitamin D administration, ten the intraperitoneal, one the subcutaneous and one the intravenous. A significant decrease of peritonitis risk was observed in two studies. Proteinuria decreased in four studies and remained stable in one study. Peritoneal protein loss decreased in one study and was stable in two studies. Studies on the therapeutic effects of vitamin D in PD are limited and describe small population samples. Moreover, vitamin D compounds do not consistently reduce PTH levels. The administration of active vitamin D in PD may have interesting pleiotropic effects such as decreasing proteinuria and peritoneal protein loss. According to these effects, vitamin D could help to preserve residual renal function and ensure efficient peritoneal membrane dialysance. PMID:25012237

Russo, Roberto; Ruospo, Marinella; Cozzolino, Mario; De Nicola, Luca; Icardi, Andrea; Paoletti, Ernesto; Mazzaferro, Sandro

2014-10-01

17

Vitamin D Status among Thai School Children and the Association with 1,25-Dihydroxyvitamin D and Parathyroid Hormone Levels  

PubMed Central

In several low latitude countries, vitamin D deficiency is emerging as a public health issue. Adequate vitamin D is essential for bone health in rapidly growing children. In the Thai population, little is known about serum 25-hydroxyvitamin D [25(OH)D] status of infants and children. Moreover, the association between 25(OH)D and the biological active form of 1,25-dihydroxyvitamin D [1,25(OH)]2D is not clear. The specific aims of this study were to characterize circulating serum 25(OH)D, 1,25(OH)2D and their determinants including parathyroid hormone (PTH), age, sex, height and body mass index (BMI) in 529 school-aged Thai children aged 6–14 y. Adjusted linear regression analysis was performed to examine the impact of age and BMI, and its interaction with sex, on serum 25(OH)D concentrations and 1,25(OH)2D concentrations. Serum 25(OH)D, 1,25(OH)2D and PTH concentrations (geometric mean ± geometric SD) were 72.7±1.2 nmol/L, 199.1±1.3 pmol/L and 35.0±1.5 ng/L, respectively. Only 4% (21 of 529) participants had a serum 25(OH)D level below 50 nmol/L. There was statistically significant evidence for an interaction between sex and age with regard to 25(OH)D concentrations. Specifically, 25(OH)D concentrations were 19% higher in males. Moreover, females experienced a statistically significant 4% decline in serum 25(OH)D levels for each increasing year of age (P?=?0.001); no decline was seen in male participants with increasing age (P?=?0.93). When BMI, age, sex, height and serum 25(OH)D were individually regressed on 1,25(OH)2D, height and sex were associated with 1,25(OH)2D with females exhibiting statistically significantly higher serum 1,25(OH)2D levels compared with males (P<0.001). Serum 1,25(OH)2D among our sample of children exhibiting fairly sufficient vitamin D status were higher than previous reports suggesting an adaptive mechanism to maximize calcium absorption. PMID:25111832

Houghton, Lisa A.; Gray, Andrew R.; Harper, Michelle J.; Winichagoon, Pattanee; Pongcharoen, Tippawan; Gowachirapant, Sueppong; Gibson, Rosalind S.

2014-01-01

18

Relationships among vitamin D levels, parathyroid hormone, and calcium absorption in young adolescents  

Technology Transfer Automated Retrieval System (TEKTRAN)

BACKGROUND: Evidence suggests that vitamin D status in adults, as assessed by serum 25-hydroxyvitamin D (25-OHD), is positively associated with calcium absorption fraction and inversely associated with serum PTH. Few comparable pediatric data exist. OBJECTIVES: The objective of this study was to ev...

19

R990G Polymorphism of Calcium Sensing Receptor Gene Is Associated with High Parathyroid Hormone Levels in Subjects with Vitamin D Deficiency: A Cross-Sectional Study  

PubMed Central

Single nucleotide polymorphisms (SNPs), R990G and A986S of the calcium sensing receptor (CaSR) gene, are shown to influence response of parathyroid hormone (PTH) in subjects with optimal vitamin D levels. This cross-sectional study was conducted in subjects with vitamin D deficiency (VDD) to observe associations between CaSR polymorphisms, plasma iPTH, and serum calcium levels. Adult females (n = 140) with known VDD, intact parathyroid hormone (iPTH), and calcium levels were recruited for genotype analysis. The frequencies of the 986 alleles GG, GT, and TT were 68%, 25%, and 7%, respectively, whereas the frequencies of the 990 alleles AA, AG, and GG were 80%, 8.9%, and 11.1%, respectively. The subjects with GG genotype of R990G polymorphism had higher iPTH levels (148.65 versus 91.47 and 86.1?pg/mL for GG versus AA, AG, resp., P = 0.008) and lower calcium levels (8.4 versus 9.04 and 9.07?mg/dL for GG versus AA, AG, resp., P = 0.002). No such association of A986S polymorphism with plasma iPTH or serum calcium levels was observed in the present study. Patients with VDD bearing the GG genotype of R990G SNPs are prone to have higher iPTH levels and lower calcium.

Majid, Hafsa; Khan, Aysha Habib

2015-01-01

20

The Effect of Vitamin C on Parathyroid Hormone in Patients on Hemodialysis With Secondary Hyperparathyroidism: A Double Blind, Placebo-Controlled Study  

PubMed Central

Background Secondary hyperparathyroidism (SHPT) is a prevalent disorder in patients with chronic kidney disease. It is proffered that there is a contradictory relation between serum level of vitamin C and parathyroid hormone (PTH) in hemodialysis patients with secondary hyperparathyroidism. Objectives The goal of this study was to assess the effects of the supplemental vitamin C on parathyroid hormone among hemodialysis patients with secondary hyperparathyroidism. Patients and Methods This randomized, placebo-controlled, double-blind and parallel-group trial was conducted on 82 hemodialysis patients with serum levels of PTH more than 200 pg/mL. In intervention group, 250 mg vitamin C was injected three times a week for 8 weeks in a row immediately at the end of each dialysis session via the intravenous route. In the control group, same term of placebo saline was injected. Results The mean of serum PTH was 699.81 (± 318.8) and 596.03 (± 410.7) pg/mL in intervention and control groups respectively at baseline (reference range, 6 to 66 pg/mL), and at the end of study it changed to 441.4 and 424.6 in these groups. The values of serum Calcium and Phosphate did not significantly change during the study (8.4 ± 0.6 mg/dL versus 8.1 ± 0.8 mg/dL, P = 0.39; 5.89 ± 1.7 mg/dL versus 5.9 ± 1.9 mg/dL, P = 0.08, respectively). Conclusions This study finding does not warranted therapeutic effect of vitamin C on secondary hyperparathyroidism. PMID:24693502

Biniaz, Vajihe; Nemati, Eghlim; Tayebi, Ali; Sadeghi Shermeh, Mehdi; Ebadi, Abbas

2013-01-01

21

The impact of vitamin D status on the relative increase in fibroblast growth factor 23 and parathyroid hormone in chronic kidney disease.  

PubMed

Fibroblast growth factor (FGF) 23 is an important regulator of phosphaturia. Its serum level was found to increase before that of parathyroid hormone (PTH) in early chronic kidney disease (CKD) in some but not all previous studies. As vitamin D insufficiency is associated with elevated PTH, we determined the effect of vitamin D status on FGF23 and PTH levels in relation to glomerular filtration rate (GFR) in people with CKD stage 3. Serum intact FGF23, PTH, and 25(OH)vitamin D3 were measured in 1664 patients who were prospectively recruited from primary care. Mean or median values for key variables were an age of 73 years, estimated GFR (eGFR) of 53?ml/min per 1.73?m(2), PTH 46?pg/ml, FGF23 42?pg/ml, and 25(OH)vitamin D3 53?nmol/l. FGF23 and PTH concentrations were elevated in similar proportions of people with lower eGFR in the whole cohort. However, when 752 people with vitamin D insufficiency or deficiency were excluded, FGF23 was elevated in a greater proportion than PTH at all levels of eGFR. Conversely, among people with vitamin D insufficiency, PTH was elevated in a greater proportion than FGF23 at all GFR levels of ?40?ml/min per 1.73?m(2). In this cohort, we were able to triangulate the relationship between 25(OH)vitamin D3, PTH, and FGF23, showing that vitamin D status critically determines whether FGF23 or PTH becomes elevated first in the context of lower GFR. Future studies of FGF23 in people with CKD should routinely determine their vitamin D status. PMID:24429404

Taal, Maarten W; Thurston, Victoria; McIntyre, Natasha J; Fluck, Richard J; McIntyre, Christopher W

2014-08-01

22

Parathyroid hormone - Secretion and metabolism in vivo.  

NASA Technical Reports Server (NTRS)

Gel filtration and radioimmunoassay were used to determine the molecular size and immunochemical reactivity of parathyroid hormone present in gland extracts, in the general peripheral circulation, and in parathyroid effluent blood from patients with hyperparathyroidism, as well as from calves and from cattle. It was found that parathyroid hormone secreted from the parathyroids in man and cattle is at least as large as the molecule extracted from normal bovine glands. However, once secreted into the circulation the hormone is cleaved, and one or more fragments, immunologically, dissimilar to the originally secreted hormone, constitute the dominant form of circulating immunoreactive hormone.

Habener, J. F.; Powell, D.; Murray, T. M.; Mayer, G. P.; Potts, J. T., Jr.

1971-01-01

23

Parathyroid Hormone Levels and Cognition  

NASA Technical Reports Server (NTRS)

Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, p<.01). There was no significant group difference in ionized calcium levels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

2009-01-01

24

21 CFR 862.1545 - Parathyroid hormone test system.  

Code of Federal Regulations, 2012 CFR

... 2012-04-01 false Parathyroid hormone test system. 862.1545 Section 862...Test Systems § 862.1545 Parathyroid hormone test system. (a) Identification. A parathyroid hormone test system is a device intended to...

2012-04-01

25

Alterations in vitamin D metabolite, parathyroid hormone and fibroblast growth factor-23 concentrations in sclerostin-deficient mice permit the maintenance of a high bone mass.  

PubMed

Humans with mutations of the sclerostin (SOST) gene, and knockout animals in which the Sost gene has been experimentally deleted, exhibit an increase in bone mass. We review the mechanisms by which Sost knockout mice are able to accrete increased amounts of calcium and phosphorus required for the maintenance of a high bone mass. Recently published information from our laboratory, shows that bone mass is increased in Sost-deficient mice through an increase in osteoblast and a decrease in osteoclast activity, which is mediated by activation of ?-catenin and an increase in prostacyclin synthesis in osteocytes and osteoblasts. The increases in calcium and phosphorus retention required for enhanced bone mineral accretion are brought about by changes in the vitamin D endocrine system, parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23). Thus, in Sost knockout mice, concentrations of serum 1,25-dihydroxyvitamin D (1,25(OH)2D) are increased and concentrations of FGF-23 are decreased thereby allowing a positive calcium and phosphorus balance. Additionally, in the absence of Sost expression, urinary calcium is decreased, either through a direct effect of sclerostin on renal calcium handling, or through its effect on the synthesis of 1,25(OH)2D. Adaptations in vitamin D, PTH and FGF-23 physiology occur in the absence of sclerostin expression and mediate increased calcium and phosphorus retention required for the increase in bone mineralization. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. PMID:25446885

Ryan, Zachary C; Craig, Theodore A; McGee-Lawrence, Meghan; Westendorf, Jennifer J; Kumar, Rajiv

2014-11-22

26

Vitamin D3 Decreases Parathyroid Hormone in HIV-Infected Youth Being Treated With Tenofovir: A Randomized, Placebo-Controlled Trial  

PubMed Central

Background.?The study goal was to determine the effect of vitamin D (VITD) supplementation on tubular reabsorption of phosphate (TRP), parathyroid hormone (PTH), bone alkaline phosphatase (BAP), and C-telopeptide (CTX) in youth infected with human immunodeficiency virus (HIV) receiving and not receiving combination antiretroviral therapy (cART) containing tenofovir disoproxil fumarate (TDF). Methods.?This randomized, double-blind, placebo-controlled multicenter trial enrolled HIV-infected youth 18–25 years based on stable treatment with cART containing TDF (n = 118) or no TDF (noTDF; n = 85), and randomized within those groups to vitamin D3, 50 000 IU (n = 102) or placebo (n = 101), administered at 0, 4, and 8 weeks. Outcomes included change in TRP, PTH, BAP, and CTX from baseline to week 12 by TDF/noTDF; and VITD/placebo. Results.?At baseline, VITD and placebo groups were similar except those on TDF had lower TRP and higher PTH and CTX. At week 12, 95% in the VITD group had sufficient serum 25-hydroxy vitamin D (25-OHD; ?20 ng/mL), increased from 48% at baseline, without change in placebo (P < .001). PTH decreased in the TDF group receiving VITD (P = .031) but not in the noTDF group receiving VITD, or either placebo group. The decrease in PTH with VITD in those on TDF occurred with insufficient and sufficient baseline 25-OHD (mean PTH change, ?7.9 and ?6.2 pg/mL; P = .031 and .053, respectively). Conclusions.?In youth on TDF, vitamin D3 supplementation decreased PTH, regardless of baseline 25-OHD concentration. Clinical Trials Registration.?NCT00490412. PMID:22267714

Stephensen, Charles B.; Hazra, Rohan; Flynn, Patricia M.; Wilson, Craig M.; Rutledge, Brandy; Bethel, James; Pan, Cynthia G.; Woodhouse, Leslie R.; Van Loan, Marta D.; Liu, Nancy; Lujan-Zilbermann, Jorge; Baker, Alyne; Kapogiannis, Bill G.; Mulligan, Kathleen

2012-01-01

27

Parathyroid hormone levels predict posttotal thyroidectomy hypoparathyroidism.  

PubMed

We hypothesized that parathyroid hormone (PTH) determination would be the most effective strategy to identify posttotal thyroidectomy hypoparathyroidism (PTTHP) compared with other clinical and laboratory parameters. We retrospectively reviewed our recent experience with total thyroidectomy. We recorded demographics, malignancy, thyroid weight, parathyroid autotransplantation, hospital stay, use of postoperative calcium and hormonally active vitamin D3 (calcitriol), and postoperative serum calcium and PTH levels. Patients were divided into two groups depending on whether supplemental calcitriol was required to maintain eucalcemia and therefore reflecting the diagnosis of PTTHP. From October 2010 to June 2013, a total of 202 total thyroidectomies were performed. Twenty-four patients (12%) developed PTTHP and required calcitriol replacement. Logistic regression analysis revealed that only postoperative calcium levels (P = 0.02) and PTH levels (P < 0.0001) statistically significantly predicted PTTHP. Twenty-two of 29 patients with PTH 13 pg/mL or less had PTTHP. Only two of 173 patients with a PTH level greater than 13 pg/mL were diagnosed with PTTHP. We recommend using PTH levels after total thyroidectomy to determine which patients will have hypoparathyroidism requiring calcitriol therapy. An early determination of PTTHP allows for prompt management that can shorten hospital stay and improve outcomes. PMID:25105405

Rivere, Amy E; Brooks, Ashton J; Hayek, Genevieve A; Wang, Heng; Corsetti, Ralph L; Fuhrman, George M

2014-08-01

28

Calcium and vitamin D supplementation maintains parathyroid hormone and improves bone density during initial military training: a randomized, double-blind, placebo controlled trial.  

PubMed

Calcium and vitamin D are essential nutrients for bone health. Periods of activity with repetitive mechanical loading, such as military training, may result in increases in parathyroid hormone (PTH), a key regulator of Ca metabolism, and may be linked to the development of stress fractures. Previous studies indicate that consumption of a Ca and vitamin D supplement may reduce stress fracture risk in female military personnel during initial military training, but circulating markers of Ca and bone metabolism and measures of bone density and strength have not been determined. This randomized, double-blind, placebo-controlled trial sought to determine the effects of providing supplemental Ca and vitamin D (Ca+Vit D, 2000mg and 1000IU/d, respectively), delivered as 2 snack bars per day throughout 9weeks of Army initial military training (or basic combat training, BCT) on PTH, vitamin D status, and measures of bone density and strength in personnel undergoing BCT, as well as independent effects of BCT on bone parameters. A total of 156 men and 87 women enrolled in Army BCT (Fort Sill, OK; 34.7°N latitude) volunteered for this study. Anthropometric, biochemical, and dietary intake data were collected pre- and post-BCT. In addition, peripheral quantitative computed tomography was utilized to assess tibia bone density and strength in a subset of volunteers (n=46). Consumption of supplemental Ca+Vit D increased circulating ionized Ca (group-by-time, P=0.022), maintained PTH (group-by-time, P=0.032), and increased the osteoprotegerin:RANKL ratio (group-by-time, P=0.006). Consistent with the biochemical markers, Ca+Vit D improved vBMD (group-by-time, P=0.024) at the 4% site and cortical BMC (group-by-time, P=0.028) and thickness (group-by-time, P=0.013) at the 14% site compared to placebo. These data demonstrate the benefit of supplemental Ca and vitamin D for maintaining bone health during periods of elevated bone turnover, such as initial military training. This trial was registered with ClincialTrials.gov, NCT01617109. PMID:25118085

Gaffney-Stomberg, Erin; Lutz, Laura J; Rood, Jennifer C; Cable, Sonya J; Pasiakos, Stefan M; Young, Andrew J; McClung, James P

2014-11-01

29

Biochemical markers of bone turnover, intact serum parathyroid hormone and renal calcium excretion in patients with pseudohypoparathyroidism and hypoparathyroidism before and during vitamin D treatment  

Microsoft Academic Search

In addition to the well-documented hyporesponsiveness of the kidney, resistance to parathyroid hormone (PTH) has been postulated for bone in pseudohypoparathyroidism type I (PHP). In some of these patients reduced bone density and even frank osteitis fibrosa suggest osteoclastic overactivity. To address the possibility that the skeletal system of patients with PHP may be affected by their increased PTH secretion

K. Kruse; U. Kracht; K. Wohlfart; U. Kruse

1989-01-01

30

Magnesium modulates parathyroid hormone secretion and upregulates parathyroid receptor expression at moderately low calcium concentration  

PubMed Central

Background The interest on magnesium (Mg) has grown since clinical studies have shown the efficacy of Mg-containing phosphate binders. However, some concern has arisen for the potential effect of increased serum Mg on parathyroid hormone (PTH) secretion. Our objective was to evaluate the direct effect of Mg in the regulation of the parathyroid function; specifically, PTH secretion and the expression of parathyroid cell receptors: CaR, the vitamin D receptor (VDR) and FGFR1/Klotho. Methods The work was performed in vitro by incubating intact rat parathyroid glands in different calcium (Ca) and Mg concentrations. Results Increasing Mg concentrations from 0.5 to 2 mM produced a left shift of PTH–Ca curves. With Mg 5 mM, the secretory response was practically abolished. Mg was able to reduce PTH only if parathyroid glands were exposed to moderately low Ca concentrations; with normal–high Ca concentrations, the effect of Mg on PTH inhibition was minor or absent. After 6-h incubation at a Ca concentration of 1.0 mM, the expression of parathyroid CaR, VDR, FGFR1 and Klotho (at mRNA and protein levels) was increased with a Mg concentration of 2.0 when compared with 0.5 mM. Conclusions Mg reduces PTH secretion mainly when a moderate low calcium concentration is present; Mg also modulates parathyroid glands function through upregulation of the key cellular receptors CaR, VDR and FGF23/Klotho system. PMID:24103811

Rodríguez-Ortiz, Maria E.; Canalejo, Antonio; Herencia, Carmen; Martínez-Moreno, Julio M.; Peralta-Ramírez, Alan; Perez-Martinez, Pablo; Navarro-González, Juan F.; Rodríguez, Mariano; Peter, Mirjam; Gundlach, Kristina; Steppan, Sonja; Passlick-Deetjen, Jutta; Muñoz-Castañeda, Juan R.; Almaden, Yolanda

2014-01-01

31

Skeletal responsiveness to parathyroid hormone in pseudohypoparathyroidism  

Microsoft Academic Search

Background: Although there have been some case reports suggesting that bone in patients with pseudohypoparathyroidism (PHP) might respond to parathyroid hormone (PTH), no information is available as to whether serum PTH concentration is related to bone metabolic markers or to bone mineral density (BMD) in PHP. Objective: To address these relationships, by comparing intact serum PTH, bone metabolic markers and

Masanori Kanatani; Toshitsugu Sugimoto; Hiroshi Kaji; Kazuto Ikeda; Kazuo Chihara

2001-01-01

32

No association between vitamin D deficiency and parathyroid hormone, bone density and bone turnover in a large cohort of HIV-infected men on tenofovir  

PubMed Central

Introduction Combination antiretroviral therapy (cART) may affect vitamin D [25(OH)D], parathyroid hormone (PTH), bone mineral density (BMD) and bone turnover (BT). Reduced BMD and secondary hyperparathyroidism have been reported with tenofovir (TDF). We investigated the associations between TDF and bone markers, especially in 25(OH)D-deficient patients. Materials and Methods In a single-centre longitudinal study investigating BMD in HIV-positive men, serum 25(OH)D, calcium, phosphate, PTH and alkaline phosphatase (ALP) were measured. Lumbar spine, non-dominant total hip and non-dominant femoral neck BMD (g/cm2) were measured using dual-energy X-ray absorptiometry. BT was assessed by serum type 1 procollagen (P1NP) and carboxy-terminal collagen cross-links (CTX). Mann–Whitney U tests compared serum markers and BT, and t-tests compared BMD according to TDF in all and 25(OH)D-deficient patients. Results A total of 422 men were recruited: mean age 47 (SD 9.8) years, 94% white ethnicity, 93% MSM, diagnosed HIV positive for median 9.6 (IQR 5.0,15.5) years, median CD4 547 (IQR 411,696) cells/µL, HIV RNA <40 copies/mL in 87% (96% of those on cART). 25(OH)D (nmol/L) was normal (>75), insufficient (50–75), deficient (25–50) and severely deficient (<25) in 14%, 29%, 50% and 7%, respectively. Of 381 men on cART, 77% were currently on TDF. TDF was not associated with median calcium (p=0.69) or phosphate (p=0.52), but patients had higher (but normal) median ALP [81 (IQR 69,103) vs. 73 (IQR 60,89) IU/L, p=0.005) compared to non-TDF cART. There was no difference in the association between vitamin D and PTH according to whether someone currently was (r=0.11, p=0.06, Figure 1) or was not using TDF (r=0.12, p=0.29, Figure 1). TDF was also not associated with PTH, BMD or BT in either all patients on cART (Table 1a) or in patients with 25(OH)D deficiency (Table 1b). Conclusions In this largely TDF-experienced cohort of HIV-positive men, there was no association between TDF and 25(OH)D deficiency, hyperparathyroidism, reduced BMD or increased BT, although patients on TDF had higher but normal ALP. We found no evidence to support additional monitoring of bone markers in patients on TDF regardless of 25(OH)D status. PMID:25394075

Samarawickrama, Amanda; Jose, Sophie; Sabin, Caroline; Walker-Bone, Karen; Fisher, Martin; Gilleece, Yvonne

2014-01-01

33

Serum parathyroid hormone level is associated with body mass  

Microsoft Academic Search

Abstract Objective: To study whether,serum,parathyroid,hormone,(PTH) and,serum,calcium,are associated with body mass index (BMI), and their predicting role in obesity. Design: Population based, cross-sectional study. Methods: In 2001 a population-based health survey was held in Tromsø, North Norway. Question- naires on medical,history and,life-style factors were completed,and,anthropometric,data were col- lected. Calcium,and,vitamin,D intakes and,a physical,activity score were,calculated. Serum calcium,and PTH were,measured,in a subset of

Clinical S Tudy; Elena Kamycheva; Johan Sundsfjord; Rolf Jorde

34

25-Hydroxyvitamin D, parathyroid hormone, and functional recovery after hip fracture in elderly patients  

Microsoft Academic Search

There is increasing interest in the effects of vitamin D and parathyroid hormone (PTH) on extraskeletal tissues, including\\u000a the muscle. These effects may explain impairment in functional ability found in vitamin D-deficient subjects. Our aim was\\u000a to investigate the roles of vitamin D and PTH in affecting the ability to perform activities of daily living after hip fracture.\\u000a We studied

Marco Di Monaco; Fulvia Vallero; Roberto Di Monaco; Rosa Tappero; Alberto Cavanna

2006-01-01

35

Suppression of Serum Parathyroid Hormone Levels by Intravenous Alphacalcidol in Uremic Patients on Maintenance Hemodialysis  

Microsoft Academic Search

Seven patients on chronic hemodialysis were given alphacalcidol (1?-OH-vitamin D3) intravenously in a pilot study during 3 months. Before treatment all patients had serum calcium values within the normal range, but elevated levels of parathyroid hormone (PTH). When serum calcium was raised above the normal range by treatment with alphacalcidol, all patients displayed marked suppression of PTH levels with a

Lars Lind; Bo Wengle; Leif Wide; Ulf Wrege; Sverker Ljunghall

1988-01-01

36

Linear growth in relation to the circulating concentrations of insulin-like growth factor I, parathyroid hormone, and 25-hydroxy vitamin D in children with nutritional rickets before and after treatment: endocrine adaptation to vitamin D deficiency  

Microsoft Academic Search

The objective of the study was to determine the degree of linear growth retardation of patients with vitamin D deficiency rickets at presentation and the magnitude of catch-up growth in relation to their calcium (Ca) homeostasis and hormones affecting it before and after treatment. This prospective study recorded the anthropometric data and measured the circulating 25-hydroxy vitamin D (25-OH-D), insulin-like

Ashraf T. Soliman; Fauzia Al Khalaf; Noura AlHemaidi; Maryam Al Ali; Mahmoud Al Zyoud; Khaled Yakoot

2008-01-01

37

The Role of Intraoperative Measurement of Parathyroid Hormone in Parathyroid Surgery  

Microsoft Academic Search

Technological developments have significantly contributed to the rapid evolution of the surgical management of parathyroid disorders. The ability to physiologically determine the intraoperative status of the patient is now possible through the assessment of changing levels of intact parathyroid hormone (PTH) during surgery. In most patients with primary hyperparathyroidism, this method provides biochemical confirmation of hyperfunctional gland removal, and is

Phillip K. Pellitteri

2008-01-01

38

Parathyroid hormone and parathyroid hormone type-1 receptor accelerate myocyte differentiation  

PubMed Central

The ZHTc6-MyoD embryonic stem cell line expresses the myogenic transcriptional factor MyoD under the control of a tetracycline-inducible promoter. Following induction, most of the ZHTc6-MyoD cells differentiate to myotubes. However, a small fraction does not differentiate, instead forming colonies that retain the potential for myocyte differentiation. In our current study, we found that parathyroid hormone type 1 receptor (PTH1R) expression in colony-forming cells at 13 days after differentiation was higher than that in the undifferentiated ZHTc6-MyoD cells. We also found that PTH1R expression was required for myocyte differentiation, and that parathyroid hormone accelerated the differentiation. Our analysis of human and mouse skeletal muscle tissues showed that most cells expressing PTH1R also expressed Pax7 and CD34, which are biomarkers of satellite cells. Furthermore, we found that parathyroid hormone treatment significantly improved muscle weakness in dystrophin-deficient mdx mice. This is the first report indicating that PTH1R and PTH accelerate myocyte differentiation. PMID:24919035

Kimura, Shigemi; Yoshioka, Kowasi

2014-01-01

39

Therapy of Hypoparathyroidism by Replacement with Parathyroid Hormone  

PubMed Central

Hypoparathyroidism (HypoPT) is a state of hypocalcemia due to inappropriate low levels of parathyroid hormone (PTH). HypoPT is normally treated by calcium supplements and activated vitamin D analogues. Although plasma calcium is normalized in response to conventional therapy, quality of life (QoL) seems impaired and patients are at increased risk of renal complications. A number of studies have suggested subcutaneous injections with PTH as an alternative therapy. By replacement with the missing hormone, urinary calcium may be lowered and QoL may improve. PTH replacement therapy (PTH-RT) possesses, nevertheless, a number of challenges. If PTH is injected only once a day, fluctuations in calcium levels may occur resulting in hypercalcemia in the hours following an injection. Twice-a-day injections seem to cause less fluctuation in plasma calcium but do stimulate bone turnover to above normal. Most recently, continuous delivery of PTH by pump has appeared as a feasible alternative to injections. Plasma calcium levels do not fluctuate, urinary calcium is lowered, and bone turnover is only stimulated modestly (into the normal range). Further studies are needed to assess the long-term effects. If beneficial, it seems likely that standard treatment of HypoPT in the future will change into replacement therapy with the missing hormone. PMID:25101193

2014-01-01

40

Negative regulation of parathyroid hormone-related protein expression by steroid hormones  

SciTech Connect

Highlights: {yields} Steroid hormones repress expression of PTHrP in the cell lines where the corresponding nuclear receptors are expressed. {yields} Nuclear receptors are required for suppression of PTHrP expression by steroid hormones, except for androgen receptor. {yields} Androgen-induced suppression of PTHrP expression appears to be mediated by estrogen receptor. -- Abstract: Elevated parathyroid hormone-related protein (PTHrP) is responsible for humoral hypercalcemia of malignancy (HHM), which is of clinical significance in treatment of terminal patients with malignancies. Steroid hormones were known to cause suppression of PTHrP expression. However, detailed studies linking multiple steroid hormones to PTHrP expression are lacking. Here we studied PTHrP expression in response to steroid hormones in four cell lines with excessive PTHrP production. Our study established that steroid hormones negatively regulate PTHrP expression. Vitamin D receptor, estrogen receptor {alpha}, glucocorticoid receptor, and progesterone receptor, were required for repression of PTHrP expression by the cognate ligands. A notable exception was the androgen receptor, which was dispensable for suppression of PTHrP expression in androgen-treated cells. We propose a pathway(s) involving nuclear receptors to suppress PTHrP expression.

Kajitani, Takashi; Tamamori-Adachi, Mimi [Department of Biochemistry, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605 (Japan)] [Department of Biochemistry, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605 (Japan); Okinaga, Hiroko [Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605 (Japan)] [Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605 (Japan); Chikamori, Minoru; Iizuka, Masayoshi [Department of Biochemistry, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605 (Japan)] [Department of Biochemistry, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605 (Japan); Okazaki, Tomoki, E-mail: okbgeni@med.teikyo-u.ac.jp [Department of Biochemistry, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605 (Japan)] [Department of Biochemistry, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605 (Japan)

2011-04-15

41

Parathyroid Carcinoma: Current Understanding and New Insights into Gene Expression and Intraoperative Parathyroid Hormone Kinetics  

PubMed Central

Parathyroid carcinoma is an indolent but ultimately life-threatening malignancy. Due to the lack of definitive diagnostic markers and overlapping clinical features of benign primary hyperparathyroidism (PHPT), this disease is often misdiagnosed as parathyroid adenoma. Therefore, a high index of suspicion preoperatively and early intraoperative recognition with en bloc surgical resection are crucial for favorable outcome. Owing to the rarity of the disease, little is known about the molecular pathogenesis of parathyroid carcinoma. Here, we review the literature to present current understanding of the disease and provide new information on gene expression and use of intraoperative parathyroid hormone (PTH) monitoring in the surgical management of this rare malignancy. Specifically, using microarray transcriptome analysis of an unequivocal case of parathyroid carcinoma and a biopsy from the same patient's normal parathyroid gland, we identify APP, CDH1, KCNJ16, and UCHL1 as differentially expressed genes in parathyroid carcinoma. Further, using case records from four cases of unequivocal parathyroid carcinoma, we compared intraoperative PTH kinetics of these patients to 475 patients with benign PHPT, and show that intraoperative PTH monitoring is accurate in predicting postoperative normocalcemia in initial en bloc operations for parathyroid carcinoma. PMID:20051478

Abdelgadir Adam, Mohamed; Untch, Brian R.

2010-01-01

42

Circulating parathyroid hormone and calcitonin in rats after spaceflight  

NASA Technical Reports Server (NTRS)

Parathyroid hormone and calcithonin, two major calcium-regulating hormones, were measured in the plasma of five experimental groups of rats to evaluate postflight calcium homeostasis after the 14-day Cosmos 2044 flight. Parathyroid hormone values were slightly higher in the flight animals (F) than in the appropriate cage and diet controls (S) (44 +/- 21 vs 21 +/- 4 pg/ml, P less than 0.05), but they were the same as in the vivarium controls (V), which had different housing and feeding schedules. The difference in F and V (22 +/- 11 vs 49 +/- 16 pg/ml, P less than 0.05) was most likely due to failure of circulating calcitonin in F to show the normal age-dependent increase which was demonstrated in age-matched controls in a separate experiment. Basal values for parathyroid hormone and calcitonin were unchanged after 2 wk of hindlimb suspension, a flight simulation model, in age-matched and younger rats. From a time course experiment serum calcium was higher and parathyroid hormone lower after 4 wk than in ambulatory controls. Postflight circulating levels of parathyroid hormone appear to reflect disturbances in calcium homeostasis from impaired renal function of undetermined cause, whereas levels of calcitonin reflect depression of a normal growth process.

Arnaud, Sara B.; Fung, Paul; Popova, Irina A.; Morey-Holton, Emily R.; Grindeland, Richard E.

1992-01-01

43

Use of parathyroid hormone in hypoparathyroidism  

PubMed Central

Hypoparathyroidism is a disorder characterized by hypocalcemia, deficient PTH, and abnormal bone remodeling. Standard treatment of hypoparathyroidism consists of oral calcium and vitamin D supplementation. However, maintaining serum calcium levels can be a challenge. In addition, concerns exist regarding hypercalciuria and ectopic calcifications that can be associated with such treatment. Hypoparathyroidism is the only classic endocrine deficiency disease for which the missing hormone, PTH, is not yet an approved treatment. This review focuses on the use of PTH in the treatment of hypoparathyroidism, in the form of teriparatide [PTH(1-34)] and the full-length molecule, PTH(1-84). Studies in hypoparathyroid subjects demonstrate that PTH(1-34) and PTH(1-84) lower or abolish supplemental calcium and vitamin D requirements as well as increase markers of bone turnover. Densitometric and histomorphometric studies in some subjects treated with PTH(1-34) and PTH(1-84) show an improvement in bone-remodeling dynamics and return of bone metabolism toward normal levels. Given the chronic nature of hypoparathyroidism, and the expectation that PTH will be used for extended periods of time in hypoparathyroidism, further studies are needed to determine the long-term safety of PTH therapy in this population. PMID:24445125

Cusano, N.E.; Rubin, M.R.; Irani, D.; Sliney, J.; Bilezikian, J.P.

2015-01-01

44

Fibroblast growth factor 23 and parathyroid hormone after treatment with active vitamin D and sevelamer carbonate in patients with chronic kidney disease stage 3b, a randomized crossover trial  

PubMed Central

Background Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that is secreted from bone and serum level increases as renal function declines. Higher levels of FGF23 are associated with increased mortality in hemodialysis-patients and in patients with chronic kidney disease (CKD) stage 2-4. The use of active vitamin D and phosphate binders as recommended in international guidelines, may affect the level of FGF23 and thereby clinical outcome. We investigated the effects of a phosphate binder and active vitamin D on the serum levels of intact FGF23 (iFGF23) and intact parathyroid hormone (iPTH) in patients with CKD stage 3b (glomerular filtration rate (GFR) 30–44 ml/min/1.73 m2). Methods Seven women and 14 men were included, mean age 65.6?±?12.2?years. They were randomized in a 1:1 ratio to receive one of two treatment sequences. Group-1 (the alphacalcidol-sevelamer carbonate group): alphacalcidol 0.25??g once daily for two weeks followed by sevelamer carbonate 800?mg TID with meals for two weeks after a two-week washout period. Group-2 (the sevelamer carbonate-alphacalcidol group): vice versa. Nineteen patients completed the study. The 25-hydroxyvitamin D level at baseline was 97.6?±?25.0?nmol/l. Results There were no treatment effects on the iFGF23 and iPTH levels overall. In group-1 the iFGF23 level was higher after treatment with alphacalcidol compared with sevelamer carbonate (mean 105.8?±?41.6 vs. 79.1?±?36.5?pg/ml, p?=?0.047 (CI: 0.4-52.9), and the iPTH level was lower (median: 26.5, range: 14.6-55.2 vs. median 36.1, range 13.4-106.9?pg/ml, p?=?0.011). In group-2 the iFGF23 level increased non-significantly after treatment with sevelamer carbonate and throughout the washout period. Conclusions In this crossover trial with alphacalcidol and sevelamer carbonate in patients with CKD stage 3b, the levels of iFGF23 were not significantly different after the two treatments. However, in the group of patients initiating therapy with sevelamer carbonate the iFGF23 levels seemed to increase while this response was mitigated in the group of patients given alphacalcidol followed by sevelamer carbonate. This may have therapeutic implications on choice of first line therapy. The number of patients is small and this conclusion is in part based on subgroup analysis. It is therefore important that these results are confirmed in larger studies. Trial registration Trial Registration Number: European Clinical Trial Database (EudraCT) 2010-020415-36 and Clinical Trials.gov NCT01231438 PMID:22742720

2012-01-01

45

Aluminum posttranscriptional regulation of parathyroid hormone synthesis: A role for the calcium-sensing receptor  

Microsoft Academic Search

Aluminum posttranscriptional regulation of parathyroid hormone synthesis: A role for the calcium-sensing receptor.BackgroundCalcium regulates parathyroid hormone (PTH) gene expression by a posttranscriptional mechanism, as well as parathyroid gland growth through the activation of the calcium-sensing receptor. Aluminum decreases both parathyroid cell proliferation and PTH levels by an unknown mechanism.MethodsTo investigate the possible role of calcium-sensing receptor in the aluminum-induced PTH

IGNACIO GONZÁLEZ-SUÁREZ; DANIEL ÁLVAREZ-HERNÁNDEZ; NATALIA CARRILLO-LÓPEZ; MANUEL NAVES-DÍAZ; JOSÉ LUIS FERNÁNDEZ-MARTÍN; Jorge B. Cannata-Andia; Jorge B. Cannata Andía

2005-01-01

46

Calcitriol, calcidiol, parathyroid hormone, and fibroblast growth factor-23 interactions in chronic kidney disease  

PubMed Central

Objective To review the inter-relationships between calcium, phosphorus, parathyroid hormone (PTH), parent and activated vitamin D metabolites (vitamin D, 25(OH)-vitamin D, 1,25(OH)2-vitamin D, 24,25(OH)2-vitamin D), and fibroblast growth factor-23 (FGF-23) during chronic kidney disease (CKD) in dogs and cats. Data Sources Human and veterinary literature. Human Data Synthesis Beneficial effects of calcitriol treatment during CKD have traditionally been attributed to regulation of PTH but new perspectives emphasize direct renoprotective actions independent of PTH and calcium. It is now apparent that calcitriol exerts an important effect on renal tubular reclamation of filtered 25(OH)-vitamin D, which may be important in maintaining adequate circulating 25(OH)-vitamin D. This in turn may be vital for important pleiotropic actions in peripheral tissues through autocrine/paracrine mechanisms that impact the health of those local tissues. Veterinary Data Synthesis Limited information is available reporting the benefit of calcitriol treatment in dogs and cats with CKD. Conclusions A survival benefit has been shown for dogs with CKD treated with calcitriol compared to placebo. The concentrations of circulating 25(OH)-vitamin D have recently been shown to be low in people and dogs with CKD and are related to survival in people with CKD. Combination therapy for people with CKD using both parental and activated vitamin D compounds is common in human nephrology and there is a developing emphasis using combination treatment with activated vitamin D and renin-angiotensin-aldosterone-system (RAAS) inhibitors. PMID:23566108

Brito Galvao, Joao F; Nagode, Larry A; Schenck, Patricia A; Chew, Dennis J

2013-01-01

47

Structural Basis for Antibody Discrimination between Two Hormones That Recognize the Parathyroid Hormone Receptor  

SciTech Connect

Parathyroid hormone-related protein (PTHrP) plays a vital role in the embryonic development of the skeleton and other tissues. When it is produced in excess by cancers it can cause hypercalcemia, and its local production by breast cancer cells has been implicated in the pathogenesis of bone metastasis formation in that disease. Antibodies have been developed that neutralize the action of PTHrP through its receptor, parathyroid hormone receptor 1, without influencing parathyroid hormone action through the same receptor. Such neutralizing antibodies against PTHrP are therapeutically effective in animal models of the humoral hypercalcemia of malignancy and of bone metastasis formation. We have determined the crystal structure of the complex between PTHrP (residues 1-108) and a neutralizing monoclonal anti-PTHrP antibody that reveals the only point of contact is an {alpha}-helical structure extending from residues 14-29. Another striking feature is that the same residues that interact with the antibody also interact with parathyroid hormone receptor 1, showing that the antibody and the receptor binding site on the hormone closely overlap. The structure explains how the antibody discriminates between the two hormones and provides information that could be used in the development of novel agonists and antagonists of their common receptor.

McKinstry, William J.; Polekhina, Galina; Diefenbach-Jagger, Hannelore; Ho, Patricia W.M.; Sato, Koh; Onuma, Etsuro; Gillespie, Matthew T.; Martin, T. John; Parker, Michael W.; (SVIMR-A); (Chugai); (Melbourne)

2009-08-18

48

Circulating levels of biologically active parathyroid hormone in rheumatic diseases.  

PubMed Central

There has been doubt as to whether elevated levels of parathyroid hormone, reported previously by radioimmunoassay, reflect increased concentrations of the biologically active hormone. The application of a recently developed, highly sensitive bioassay has shown considerable disparity between bioactivity and immunoreactivity in 5 rheumatic conditions and in normal subjects. Six patients with chondrocalcinosis had elevated levels; 3 of these did not have hypercalcaemia or any obvious cause other than possible subclinical hyperparathyroidism. One patient, assayed during an acute episode, had an elevated concentration of the hormone which reverted to normal when she was asymptomatic. Most patients with osteoarthrosis (13 our of 15) had low normal levels; 2 showed unexplained slightly elevated concentrations. Of 6 patients with haemochromatosis 3 had elevated levels, though this may have been related to the associated presence of diabetes mellitus. A third of patients with ankylosing spondylitis (10 out of 30) showed elevated parathyroid hormone levels but without hypercalcaemia. A number of spondylitic patients also showed anomalous results in this assay, possibly due to the presence of an antagonist. This would be consistent with the absence of clinical or biochemical evidence of hyperparathyroidism. PMID:6983329

Dunham, J; Bourke, B E; Bitensky, L; Chayen, J; Loveridge, N; Scott, J T

1982-01-01

49

Vitamin D: a pleiotropic hormone.  

PubMed

The secosteroid hormone 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is the natural ligand for the vitamin D receptor, a member of the nuclear receptor superfamily. Upon binding of the ligand, the vitamin D receptor heterodimerizes with the retinoid X receptor and binds to vitamin D response elements in the promoter region of target genes to induce/repress their expression. The target genes that have been identified so far are heterogeneous in nature and reflect the great spectrum of biological activities of 1,25(OH)(2)D(3). Within the last two decades, the receptor has been shown to be present not only in classical target tissues such as bone, kidney, and intestine, but also in many other nonclassical tissues, for example, in the immune system (T and B cells, macrophages, and monocytes), in the reproductive system (uterus, testis, ovary, prostate, placenta, and mammary glands), in the endocrine system (pancreas, pituitary, thyroid, and adrenal cortex), in muscles (skeletal, smooth, and heart muscles), and in brain, skin, and liver. Besides the almost universal presence of vitamin D receptors, different cell types (for example, keratinocytes, monocytes, bone, placenta) are capable of metabolizing 25-hydroxyvitamin D(3) to 1,25(OH)(2)D(3) by the enzyme 25(OH)D(3)-1alpha-hydroxylase, encoded by CYP27B1. The combined presence of CYP27B1 and the specific receptor in several tissues introduced the idea of a paracrine/autocrine role for 1,25(OH)(2)D(3). Moreover, it has been demonstrated that 1,25(OH)(2)D(3) can induce differentiation and inhibit proliferation of normal and malignant cells. Moreover, vitamin D deficiency is associated with an increased risk for nearly all major human diseases such as cancer, autoimmune diseases, cardiovascular, and metabolic diseases. In addition to the treatment of bone disorders with 1,25(OH)(2)D(3), these newly discovered functions open perspectives for the use of 1,25(OH)(2)D(3) as an immune modulator (for example, for the treatment of autoimmune diseases or prevention of graft rejection), inhibitor of cell proliferation, and inducer of cell differentiation (cancer). PMID:20182414

Verstuyf, Annemieke; Carmeliet, Geert; Bouillon, Roger; Mathieu, Chantal

2010-07-01

50

Adrenocorticotrophic hormone causes an increase in cortisol, but not parathyroid hormone, in dogs.  

PubMed

Dogs with spontaneous disorders of glucocorticoid production often have marked disturbances in calcium homeostasis. For example, hypercalcaemia is frequently observed in dogs with hypoadrenocorticism and secondary hyperparathyroidism is a common feature of canine hyperadrenocorticism. The mechanism(s) by which glucocorticoids modulate calcium homeostasis in dogs remains ill-defined. The hypothesis of this study is that a marked increase in serum cortisol concentrations would lead to an immediate negative calcium balance state which would drive a compensatory increase in parathyroid hormone (PTH) concentrations. This hypothesis was investigated by measuring serum cortisol and plasma PTH concentration in 19 dogs before and after administration of adrenocorticotrophic (ACTH) hormone. Post ACTH administration, there was a significant increase in serum cortisol, but not PTH, concentrations. The results of this study do not support the hypothesis that an increase in endogenous glucocorticoids influences calcium balance sufficiently to cause an immediate, compensatory increase in parathyroid hormone concentration. PMID:25544698

Kilpatrick, Scott; Gow, Adam G; Evans, Helen; Mellanby, Richard J

2015-02-01

51

Osteoblast hydraulic conductivity is regulated by calcitonin and parathyroid hormone  

NASA Technical Reports Server (NTRS)

It is our hypothesis that osteoblasts play a major role in regulating bone (re)modeling by regulating interstitial fluid (ISF) flow through individual bone compartments. We hypothesize that osteoblasts of the blood-bone membrane lining the bone surfaces are capable of regulating transosseous fluid flow. This regulatory function of the osteoblasts was tested in vitro by culturing a layer of rat calvarial osteoblasts on porous membranes. Such a layer of osteoblasts subjected to 7.3 mm Hg of hydrostatic pressure posed a significant resistance to fluid flow across the cell layer similar in magnitude to the resistance posed by endothelial monolayers in vitro. The hydraulic conductivity, the volumetric fluid flux per unit pressure drop, of the osteoblast layer was altered in response to certain hormones. Hydraulic conductivity decreased approximately 40% in response to 33 nM parathyroid hormone, while it exhibited biphasic behavior in response to calcitonin: increased 40% in response to 100 nM calcitonin and decreased 40% in response to 1000 nM calcitonin. Further, activation of adenylate cyclase by forskolin dramatically increased the hydraulic conductivity, while elevation of intracellular calcium, [Ca2+]i, by the calcium ionophore A23187 initially decreased the hydraulic conductivity at 5 minutes before increasing conductivity by 30 minutes. These results suggest that cyclic adenosine monophosphate (cAMP) and [Ca2+]i may mediate changes in the osteoblast hydraulic conductivity. The increase in hydraulic conductivity in response to 100 nM calcitonin and the decrease in response to PTH suggest that the stimulatory and inhibitory effects on bone formation of calcitonin and parathyroid hormone, respectively, may be due in part to alterations in bone fluid flow.

Hillsley, M. V.; Frangos, J. A.

1996-01-01

52

Modifications of position 12 in parathyroid hormone and parathyroid hormone related protein: toward the design of highly potent antagonists.  

PubMed

Truncated N-terminal fragments of parathyroid hormone (PTH), [Tyr34]bovine PTH(7-34)NH2, and parathyroid hormone related protein (PTHrP), PTHrP(7-34)NH2, inhibit [Nle8,18,[125I]iodo-Tyr34]-bPTH(1-34)NH2 binding and PTH-stimulated adenylate cyclase in bone and kidney assays. However, the receptor interactions of these peptides are 2-3 orders of magnitude weaker than those of their agonist counterparts. To produce an antagonist with increased receptor-binding affinity but lacking agonist-like properties, structure-function studies were undertaken. Glycine at position 12 (present in all homologues of PTH and in PTHrP), which is predicted in both hormones to participate in a beta-turn, was examined by substituting conformational reporters, such as D- or L-Ala, Pro, and alpha-aminoisobutyric acid (Aib), in both agonist and antagonist analogues. Except for N-substituted amino acids, which substantially diminished potency, substitutions were well tolerated, indicating that this site can accept a wide latitude of modifications. To augment receptor avidity, hydrophobic residues compatible with helical secondary structure were introduced. Incorporation of the nonnatural amino acids D-Trp, D-alpha-naphthylalanine (D-alpha-Nal), or D-beta-Nal into either [Tyr34]bPTH(7-34)NH2 or [Nle8,18,Tyr34]bPTH(7-34)NH2 resulted in antagonists that were about 10-fold more active than their respective 7-34 parent compound. Similarly, [D-Trp12]PTHrP(7-34)NH2 was 6 times more potent than the unsubstituted peptide but retained partial agonistic properties, although markedly reduced, similar to PTHrP(7-34)NH2. The antagonistic potentiating effect was configurationally specific.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2334716

Chorev, M; Goldman, M E; McKee, R L; Roubini, E; Levy, J J; Gay, C T; Reagan, J E; Fisher, J E; Caporale, L H; Golub, E E

1990-02-13

53

Influence of parathyroid hormone on bone cell ultrastructure  

SciTech Connect

A study in rats demonstrated that morphologic changes in the bone osteocytes and osteoblasts are produced following parathyroid hormone (PTH) injection into thyroparathyroidectomized animals. It further showed that similar changes occur in normal rats as the result of extended fasting. The most significant morphologic alterations involved surface microvilli and blebs as determined by scanning electron microscopy. Transmission electron microscopy studies showed alterations in the cisternae of the rough endoplasmic reticulum. Additionally, cell shape varied markedly from the control cuboidal morphology. These morphologic changes occurred during peak periods of plasma calcium change and returned to control morphology as plasma calcium levels normalized. The study supports the concept that osteocytes and lining cells on the surface of bone play a role in maintenance of plasma calcium concentrations. (JMT)

Matthews, J.L. (Baylor Univ. Medical Center, Dallas, TX); Talmage, R.V.

1981-05-01

54

Lack of a direct effect of 1,25-dihydroxycholecalciferol on parathyroid hormone secretion by normal bovine parathyroid glands.  

PubMed

Because of differing reports of an effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on parathyroid hormone (PTH) secretion, the present studies were performed in vitro using bovine parathyroid gland slices and isolated parathyroid cells. Both COOH-terminal and NH2-terminal RIAs for PTH were employed. No effect of 1,25(OH)2D3 on PTH secretion was found during a 4-h incubation of parathyroid slices in variable external calcium concentrations. The results from dual RIA measurements also showed no effect of 1,25(OH)2D3 on PTH secretion by isolated parathyroid cells during 90- to 150-min incubations with variable calcium concentrations. In addition, extensive analysis by polyacrylamide gel electrophoresis showed no effect of 1,25(OH)2D3 on cAMP generation. Whereas calcium inhibited and isoproterenol stimulated the production of cAMP, 1,25(OH)2D3 had no effect. We conclude that 1,25(OH)2D3 does not affect parathyroid gland function acutely in vitro. PMID:6893023

Golden, P; Greenwalt, A; Martin, K; Bellorin-Font, E; Mazey, R; Klahr, S; Slatopolsky, E

1980-08-01

55

The effect of continuous infusion of human parathyroid hormone on bone architecture in female mice  

E-print Network

This research sought to create an animal model of secondary hyperparathyroidism through continuous infusion of parathyroid hormone (PTH) in adult female mice, and to subsequently study the catabolic effects of PTH. Osmotic ...

Eisenberg, Rahel E. (Rahel Esther)

2009-01-01

56

Use of Reference Data in the Interpretation of Parathyroid Hormone Measurements  

PubMed Central

This report describes the development of a reporting aid for parathyroid hormone measurements. The system is based on a combination of practice statements from experienced endocrinologists and data collected from 1576 medical records. The PTH test results are categorized into compartments based on the concentration of creatinine, calcium and parathyroid hormone. Within compartments, the relative frequency of various diagnoses are tabulated along with information on how additional clinical parameters and laboratory tests affect the relative frequencies.

Klee, George; Cox, Catherine; Purnell, Don; Kao, Pai

1984-01-01

57

Structural characterization of amyloid fibrils from the human parathyroid hormone.  

PubMed

Amyloid deposits are common in various tissues as a consequence of misfolded proteins. However, secretory protein and peptides are often stored in membrane coated granules as functional amyloids. In this article, we present a detailed characterization of in vitro generated amyloid fibrils from human parathyroid hormone (hPTH(1-84)). Fully mature fibrils could be obtained after a short lag phase within less than one hour at 65°C. These fibrils showed all characteristic of a cross-? structure. Protease cleavage combined with mass spectrometry identified the central region of the peptide hormone involved in the fibril core formation. EGCG, an inhibitor of amyloid fibril formation, showed binding to residues in the peptide monomers corresponding to the later fibril core and thus explaining the inhibition of the fibril growth. Conformational and dynamic studies by solid-state NMR further corroborated the cross-? core of the fibrils, but also identified highly mobile segments with a random coil structure not belonging to the rigid fibril core. PMID:25554227

Gopalswamy, Mohanraj; Kumar, Amit; Adler, Juliane; Baumann, Monika; Henze, Mathias; Kumar, Senthil T; Fändrich, Marcus; Scheidt, Holger A; Huster, Daniel; Balbach, Jochen

2015-04-01

58

Parathyroid hormone, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentration in elderly patients.  

PubMed

In 50 patients of a geriatric hospital (33 women, aged 65-96 years, mean age 80 years, and 17 men, aged 68-91, mean age 78.3 years) calcium, albumin, phosphate, urea, creatinine, parathyroid hormone, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were determined. Forty patients with serum creatinine levels up to 1.4 mg/dl (124 mumols/l) and 10 patients with creatinine concentrations greater than or equal to 1.5 mg/dl (132 mumols/l) were evaluated. In patients with normal creatinine, a positive correlation was found between parathyroid hormone and age (r = 0.41; P less than 0.01). In patients with elevated creatinine, negative correlations were found in 1,25-dihydroxyvitamin D and calcium (r = -0.724; P less than 0.05), 1,25-dihydroxyvitamin D and creatinine (r = -0.79; P less than 0.01) and 1,25-dihydroxyvitamin D and phosphate (r = -0.87; P less than 0.002). The best correlation was observed in patients with elevated serum creatinine for 1,25-dihydroxyvitamin D and phosphate (r = -0.91; P less than 0.001). The results suggest that low levels of calcium and phosphate stimulate the 1-hydroxylation of 25-hydroxyvitamin D even in advanced age and that the calcium metabolism of these patients is frequently disturbed. Nineteen patients had low levels of 25-hydroxyvitamin D, indicating an insufficient supply of vitamin D or rare exposure to sunlight. In 49 of 50 patients, one ore more of the parameters of calcium metabolism were outside the normal range. PMID:2348646

Oster, P; Müller, T; Schmidt-Gayk, H; Schlierf, G

1990-04-17

59

High Prevalence of Low Femoral Bone Mineral Density in Elderly Women Living in Nursing Homes or Community-Dwelling: A Plausible Role of Increased Parathyroid Hormone Secretion  

Microsoft Academic Search

:   The present study was designed to visit elderly women living in nursing homes and to compare their femoral neck bone mineral\\u000a density (BMD) and circulating levels of parathyroid hormone (PTH) and 25-OH vitamin D (25-OHD) with those of subjects living\\u000a at home, in the immediate vicinity of the nursing homes. Of 1483 women, aged 70 years and older, who

J.-Y. Reginster; R. Deroisy; H. Pirenne; I. Frederick; W. Dewe; A. Albert; J. Collette; S. X. Zheng; C. Gosset

1999-01-01

60

Synthesis of fully active biotinylated analogues of parathyroid hormone and parathyroid hormone-related protein as tools for the characterization of parathyroid hormone receptors.  

PubMed

The synthesis, purification, and characterization of biotinylated analogues of parathyroid hormone (PTH) and PTH-related protein (PTHrP) are described. A novel methodology was developed which allowed the selective biotinylation during solid-phase synthesis of either the Lys13 or Lys26 residue in PTH/PTHrP sequences. Incorporation of orthogonally protected N alpha-Boc-Lys(N epsilon-Fmoc) at a selected position in the sequence, followed by selective side-chain deprotection and biotinylation of the epsilon-amino group, permitted modification of the specific lysine only. Biotinylated analogues of [Nle8,18,Tyr34]bPTH(1-34)NH2 (analogue 1a) were prepared by modification of Lys13 with a biotinyl group (analogue 1) or a biotinyl-epsilon-aminohexanoyl group (analogue 2) or at Lys26 with a biotinyl-epsilon-aminohexanoyl group (analogue 3). A biotinylated PTHrP antagonist [Leu11,D-Trp12,Lys13(N epsilon-(biotinyl-beta-Ala))]PTHrP(7-34)NH2 (analogue 5), was also prepared. In a different synthetic approach, selective modification of the thiol group of [Cys35]PTHrP(1-35)NH2, in solution, with N-biotinyl-N'-(6-maleimidohexanoyl)hydrazide, resulted in analogue 4. The high affinities of the biotinylated analogues for PTH receptors present in human osteosarcoma B-10 cells or in porcine renal cortical membranes (PRCM), were comparable to those of the underivatized parent peptides. The analogues were also highly potent in stimulation of cAMP formation (analogues 1-4) or inhibition of PTH-stimulated adenylyl cyclase (analogue 5) in B-10 cells. The most potent analogue (analogue 1) had potencies in B-10 cells (Kb = 1.5 nM, Km = 0.35 nM) and in porcine renal membranes (Kb = 0.70 nM) identical or similar to those of its parent peptide, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1314656

Roubini, E; Duong, L T; Gibbons, S W; Leu, C T; Caulfield, M P; Chorev, M; Rosenblatt, M

1992-04-28

61

Catabolic and anabolic actions of parathyroid hormone on the skeleton  

PubMed Central

PTH, an 84-amino acid peptide hormone synthesized by the parathyroid glands, is essential for the maintenance of calcium homeostasis. While in its traditional metabolic role, PTH helps to maintain the serum calcium concentration within narrow, normal limits and participates as a determinant of bone remodeling, more specific actions, described as catabolic and anabolic are also well known. Clinically, the catabolic effect of PTH is best represented by primary hyperparathyroidism (PHPT), while the osteoanabolic effect of PTH is best seen when PTH or its biological aminoterminal fragment [PTH(1–34)] is used as a therapy for osteoporosis. These dual functions of PTH are unmasked under very specific pathological (PHPT) or therapeutic conditions. At the cellular level, PTH favors bone resorption, mostly by affecting the receptor activator of nuclear factor ?-B (RANK) ligand (RANKL)-osteoprotegerin-RANK system, leading to an increase in osteoclast formation and activity. Increased bone formation due to PTH therapy is explained best by its ability to enhance osteoblastogenesis and/or osteoblast survival. The PTH-induced bone formation is mediated, in part, by a decrease in SOST/sclerostin expression in osteocytes. This review focuses on the dual anabolic and catabolic actions of PTH on bone, situations where one is enhanced over the other, and the cellular and molecular mechanisms by which these actions are mediated. PMID:21946081

Silva, B.C.; Costa, A.G.; Cusano, N.E.; Kousteni, S.; Bilezikian, J.P.

2015-01-01

62

Parathyroid hormone-related protein is required for tooth eruption  

PubMed Central

Parathyroid hormone (PTH)-related protein (PTHrP)-knockout mice die at birth with a chondrodystrophic phenotype characterized by premature chondrocyte differentiation and accelerated bone formation, whereas overexpression of PTHrP in the chondrocytes of transgenic mice produces a delay in chondrocyte maturation and endochondral ossification. Replacement of PTHrP expression in the chondrocytes of PTHrP-knockout mice using a procollagen II-driven transgene results in the correction of the lethal skeletal abnormalities and generates animals that are effectively PTHrP-null in all sites other than cartilage. These rescued PTHrP-knockout mice survive to at least 6 months of age but are small in stature and display a number of developmental defects, including cranial chondrodystrophy and a failure of tooth eruption. Teeth appear to develop normally but become trapped by the surrounding bone and undergo progressive impaction. Localization of PTHrP mRNA during normal tooth development by in situ hybridization reveals increasing levels of expression in the enamel epithelium before the formation of the eruption pathway. The type I PTH/PTHrP receptor is expressed in both the adjacent dental mesenchyme and in the alveolar bone. The replacement of PTHrP expression in the enamel epithelium with a keratin 14-driven transgene corrects the defect in bone resorption and restores the normal program of tooth eruption. PTHrP therefore represents an essential signal in the formation of the eruption pathway. PMID:9751753

Philbrick, William M.; Dreyer, Barbara E.; Nakchbandi, Inaam A.; Karaplis, Andrew C.

1998-01-01

63

Biological activity of parathyroid hormone antagonists substituted at position 13.  

PubMed

Lysine occupies position 13 in the parathyroid hormone (PTH) antagonist, [Nle8,18,Tyr34]bPTH(7-34)NH2. Acylation of the epsilon-amino group in lysine 13 by a hydrophobic moiety is well tolerated in terms of bioactivity: the analog [Nle8,18, D-Trp12,Lys 13 (epsilon-3-phenylpropanoyl),Tyr34]bPTH(7-34)NH2 is equivalent to the parent peptide in its affinity for PTH receptors and its ability to inhibit PTH-stimulated adenylate cyclase in both kidney- and bone-based assays. Truncation of this peptide by deletion of phenylalanyl7 with concomitant removal of the amino-terminal alpha-amino group yielded the analog desamino[Nle8,18,D-Trp12,Lys13 (epsilon-3-phenylpropanoyl),Tyr34]bPTH(8-34)NH2, an antagonist of high potency in vitro (Kb = 4 and 9 nM, Ki = 73 and 3.5 nM in kidney- and bone-based assays, respectively). Also this analog is potentially stable to aminopeptidases present in many biological systems. PMID:1647004

Chorev, M; Roubini, E; McKee, R L; Gibbons, S W; Reagan, J E; Goldman, M E; Caulfield, M P; Rosenblatt, M

1991-01-01

64

Parathyroid hormone is not an inhibitor of lipoprotein lipase activity.  

PubMed

The reduced lipoprotein lipase (LPL) activities in uraemia are reflected by increased serum triglyceride concentrations and reduced HDL cholesterol concentrations. Both hyperparathyroidism and circulating inhibitor(s) of LPL have been associated with the disturbances of lipid metabolism in uraemia. The aim of the present study was to investigate if parathyroid hormone (PTH) had an inhibitory effect on LPL activity. Plasma post-heparin LPL activities, plasma LPL inhibitory activities, serum PTHintact and serum PTHC-terminal concentrations were analysed in 20 patients on haemodialysis and 20 healthy controls. The effects of purified, human PTHintact and a carboxyterminal fragment of PTH (PTH39-84) on LPL activities in post-heparin plasma from healthy individuals and on the enzyme activity of purified, bovine milk LPL, activated with apolipoprotein CII, were studied. Patients had significantly higher plasma LPL inhibitory activities than controls, but there was no correlation between plasma LPL inhibitory activities and serum PTH concentrations. Neither PTHintact nor PTH39-84 had a significant effect on LPL activities in vitro. Thus there was no evidence of a direct inhibition of LPL activity by PTH under the present in-vivo or in-vitro conditions. PMID:7870347

Arnadottir, M; Nilsson-Ehle, P

1994-01-01

65

Vitamin D, steroid hormones, and autoimmunity.  

PubMed

The endogenous serum metabolite of vitamin D (calcitriol, 1,25(OH)2 D3 ) is considered a true steroid hormone (D hormone), and like glucocorticoids (GCs) and gonadal hormones, may exert several immunomodulatory activities. Serum vitamin D deficiency (25(OH) D), and therefore reduced 1,25(OH)2 D3 availability, is considered a risk factor for several chronic/inflammatory or autoimmune conditions, including infectious diseases, type 1 diabetes, multiple sclerosis, and especially autoimmune rheumatic diseases (ARD). In ARD in particular, 1,25(OH)2 D3 regulates both innate and adaptive immunity, potentiating the innate response (antimicrobial activity) but reducing adaptive immunity (antigen presentation, T and B cell activities). Regarding a possible synergism between vitamin D and GCs, several studies show that 1,25(OH)2 D3 has significant additive effects on dexamethasone-mediated inhibition of human lymphocyte and monocyte proliferation. Conversely, vitamin D deficiency seems to play a role in increasing autoantibody production by B cells, and seasonal vitamin D declines may trigger flares in ARD, as recently shown. Finally, 1,25(OH)2 D3 seems to reduce aromatase activity and limit the negative effects related to increased peripheral estrogen metabolism (cell proliferation, B cell overactivity). PMID:24739090

Cutolo, Maurizio; Paolino, Sabrina; Sulli, Alberto; Smith, Vanessa; Pizzorni, Carmen; Seriolo, Bruno

2014-05-01

66

[Parathyroid hormone values in thyroid gland surgeries by harmonic scalpel and by conventional methods].  

PubMed

We have examined if there are any differences in intraoperative and early postoperative concentrations of parathyroid hormone between the first group of patients, who had thyroidectomy surgery performed by harmonic scalpel, and the second group of patients operated on by standard techniqes with the use of electrocoagulation and ligature as primary hemostatic procedures. All the patients having total thyroidectomy had their blood taken in four measurement points; immediately after the induction anesthesia, 10 minutes after the first thyroid gland lobe removal, 10 minutes after total thyroid gland removal and 24 hours after the surgery. The blood samples were used to determine concentrations of the parathyroid hormone by an immunoradiometric test. The concentration comparison of parathyroid hormone between the first and the second group has not shown statistically significant difference for any of the four measurement points. The concentration comparison of parathyroid hormone within the same groups in relation to preoperational values (the first measurement point) has shown that in both groups the parathyroid hormone concentration, in all three post-incision measurement points, has been significantly lower in relation to the concentration measured before the surgery (p < 0.0005). PMID:24490330

Grabovac, Stjepan; Prgomet, Drago; Janjanin, Sasa; Hadzibegovi?, Ana Dani?

2013-01-01

67

Suppression of serum parathyroid hormone levels by intravenous alphacalcidol in uremic patients on maintenance hemodialysis. A pilot study.  

PubMed

Seven patients on chronic hemodialysis were given alphacalcidol (1 alpha-OH-vitamin D3) intravenously in a pilot study during 3 months. Before treatment all patients had serum calcium values within the normal range, but elevated levels of parathyroid hormone (PTH). When serum calcium was raised above the normal range by treatment with alphacalcidol, all patients displayed marked suppression of PTH levels with a mean reduction of 40 +/- 20% (SD; p less than 0.01). When the dose of alphacalcidol was reduced so that the serum calcium values were kept at the upper limit of the normal range, a partial return towards pretreatment values of PTH was seen but the levels were still lowered (p less than 0.05). Thus, intravenous administration of the vitamin D compound appeared to be useful for the management of secondary hyperparathyroidism in patients on dialysis. A direct effect of alphacalcidol on the parathyroid glands could, however, not be distinguished from the calcemic action. PMID:3362275

Lind, L; Wengle, B; Wide, L; Wrege, U; Ljunghall, S

1988-01-01

68

Calcium-sensing receptor activation in chronic kidney disease: effects beyond parathyroid hormone control.  

PubMed

Secondary hyperparathyroidism (SHPT) is an important complication of advanced chronic kidney disease (CKD). Cinacalcet, an allosteric modulator of the calcium-sensing receptor (CaSR) expressed in parathyroid glands, is the only calcimimetic approved to treat SHPT in patients on dialysis. By enhancing CaSR sensitivity for plasma extracellular calcium (Ca(2+)0), cinacalcet reduces serum parathyroid hormone, Ca(2+)0, and serum inorganic phosphorous concentrations, allowing better control of SHPT and CKD-mineral and bone disorders. Of interest, the CaSR also is expressed in a variety of tissues where its activation regulates diverse cellular processes, including secretion, apoptosis, and proliferation. Thus, the existence of potential off-target effects of cinacalcet cannot be neglected. This review summarizes our current knowledge concerning the potential role(s) of the CaSR expressed in various tissues in CKD-related disorders, independently of parathyroid hormone control. PMID:25498383

Massy, Ziad A; Hénaut, Lucie; Larsson, Tobias E; Vervloet, Marc G

2014-11-01

69

Temporal trends and determinants of longitudinal change in 25-hydroxyvitamin D and parathyroid hormone levels.  

PubMed

Vitamin D is essential for facilitating calcium absorption and preventing increases in parathyroid hormone (PTH), which can augment bone resorption. Our objectives were to examine serum levels of 25-hydroxyvitamin D [25(OH)D] and PTH, and factors related to longitudinal change in a population-based cohort. This is the first longitudinal population-based study looking at PTH and 25(OH)D levels. We analyzed 3896 blood samples from 1896 women and 829 men in the Canadian Multicentre Osteoporosis Study over a 10-year period starting in 1995 to 1997. We fit hierarchical models with all available data and adjusted for season. Over 10 years, vitamin D supplement intake increased by 317 (95% confidence interval [CI] 277 to 359) IU/day in women and by 193 (135 to 252) IU/day in men. Serum 25(OH)D (without adjustment) increased by 9.3 (7.3 to 11.4) nmol/L in women and by 3.5 (0.6 to 6.4) nmol/L in men but increased by 4.7 (2.4 to 7.0) nmol/L in women and by 2.7 (-0.6 to 6.2) nmol/L in men after adjustment for vitamin D supplements. The percentage of participants with 25(OH)D levels <50 nmol/L was 29.7% (26.2 to 33.2) at baseline and 19.8% (18.0 to 21.6) at year 10 follow-up. PTH decreased over 10 years by 7.9 (5.4 to 11.3) pg/mL in women and by 4.6 (0.2 to 9.0) pg/mL in men. Higher 25(OH)D levels were associated with summer, younger age, lower body mass index (BMI), regular physical activity, sun exposure, and higher total calcium intake. Lower PTH levels were associated with younger age and higher 25(OH)D levels in both women and men and with lower BMI and participation in regular physical activity in women only. We have observed concurrent increasing 25(OH)D levels and decreasing PTH levels over 10 years. Secular increases in supplemental vitamin D intake influenced both changes in serum 25(OH)D and PTH levels. PMID:22407786

Berger, Claudie; Greene-Finestone, Linda S; Langsetmo, Lisa; Kreiger, Nancy; Joseph, Lawrence; Kovacs, Christopher S; Richards, J Brent; Hidiroglou, Nick; Sarafin, Kurtis; Davison, K Shawn; Adachi, Jonathan D; Brown, Jacques; Hanley, David A; Prior, Jerilynn C; Goltzman, David

2012-06-01

70

Impact of calcium and vitamin D insufficiencies on serum parathyroid hormone and bone mineral density: analysis of the 4th & 5th Korean National Health and Nutrition Examination Survey  

Technology Transfer Automated Retrieval System (TEKTRAN)

The relative contributions of calcium and vitamin D to calcium metabolism and bone mineral density (BMD) have been examined previously, but not in a population with very low calcium intake. To determine the relative importance of dietary calcium intake and serum 25-hydroxyvitamin D [25(OH)D] concent...

71

Gamma Probe Guided Minimally Invasive Parathyroidectomy without Quick Parathyroid Hormone Measurement in the Cases of Solitary Parathyroid Adenomas  

PubMed Central

Objective: In this study, our aim was to study the efficiency of gamma probe guided minimally invasive parathyroidectomy (GP-MIP), conducted without the intra-operative quick parathyroid hormone (QPTH) measurement in the cases of solitary parathyroid adenomas (SPA) detected with USG and dual phase 99mTc-MIBI parathyroid scintigraphy (PS) in the preoperative period. Material and Methods: This clinical study was performed in 31 SPA patients (27 female, 4 male; mean age 51±11years) between February 2006 and January 2009. All patients were operated within 30 days after the detection of the SPA with dual phase 99mTc-MIBI PS and USG. The GP-MIP was done 90-120 min after the iv injection of 740 MBq 99mTc-MIBI. In all cases, except 1 patient, the GP-MIP was performed under local anesthesia; due to the enormity of size of SPA, then general anesthesia is chosen. Results: The operation time was 30-60 min, mean 38,2±7 min. In the first postoperative day, there was a more than 50% decrease in PTH levels in all patients and all but one had normal serum calcium levels. Transient hypocalcemia was detected in one patient. Conclusion: GP-MIP without intra-operative QPTH measurement is a suitable method in the surgical treatment of SPA detected by dual phase 99mTc-MIBI PS and USG. Conflict of interest:None declared. PMID:23610724

Karya?ar, Sava?; Karya?ar, Sevda S; Yalç?n, Orhan; Yüney, Enis; Mülaz?mo?lu, Mehmet; Özpaçac?, Tevfik; Karatepe, O?uzhan; Özdenkaya, Ya?ar

2013-01-01

72

Parathyroid Hormone Effect on the Fragility of Human Young and Old Red Blood Cells in Uremia  

Microsoft Academic Search

Parathyroid hormone (PTH) is elevated in patients with chronic renal failure (CRF) and was suggested to be one of the factors responsible for the anemic syndrome of these patients because it raises the osmotic fragility of the red blood cells (RBC). In the present study, the youngest and oldest RBC were separated from circulating erythrocytes by high-speed centrifugation. The age

T. Malachi; E. Bogin; U. Gafter; J. Levi

1986-01-01

73

Plasma calcitonin and parathyroid hormone levels in growing pigs on different diets. I. —  

E-print Network

Plasma calcitonin and parathyroid hormone levels in growing pigs on different diets. I. — High phosphorus diet A. POINTILLART J. M. GAREL L. GUEGUEN Colette COLIN Station de Recherches de pigs were fed a control diet containing 0.6 p. 100 phosphorus and then given a high phosphorus diet

Paris-Sud XI, Université de

74

Preoperative Localization and Intraoperative Parathyroid Hormone Assay in Korean Patients with Primary Hyperparathyroidism  

PubMed Central

Background The intraoperative parathyroid hormone (IOPTH) assay is widely used in patients with primary hyperparathyroidism (PHPT). We investigated the usefulness of the IOPTH assay in Korean patients with PHPT. Methods We retrospectively reviewed the data of 33 patients with PHPT who underwent parathyroidectomy. Neck ultrasonography (US) and 99mTc-sestamibi scintigraphy (MIBI scan) were performed preoperatively and IOPTH assays were conducted. Results The sensitivity of neck US and MIBI scans were 91% and 94%, respectively. A 50% decrease in parathyroid hormone (PTH) levels 10 minutes after excision of the parathyroid gland was obtained in 91% (30/33) of patients and operative success was achieved in 97% (32/33) of patients. The IOPTH assay was 91% true-positive, 3% true-negative, 0% false-positive, and 6% false-negative. The overall accuracy of the IOPTH assay was 94%. In five cases with discordant neck US and MIBI scan results, a sufficient decrease in IOPTH levels helped the surgeon confirm the complete excision of the parathyroid gland with no additional neck exploration. Conclusion The IOPTH assay is an accurate tool for localizing hyperfunctioning parathyroid glands and is helpful for evaluating cases with discordant neck US and MIBI scan results. PMID:25325266

Cho, Eirie; Chang, Jung Mi; Yoon, Seok Young; Lee, Gil Tae; Ku, Yun Hyi; Kim, Hong Il; Lee, Myung-Chul; Lee, Guk Haeng

2014-01-01

75

DLC1-dependent parathyroid hormone–like hormone inhibition suppresses breast cancer bone metastasis  

PubMed Central

Bone metastasis is a frequent complication of breast cancer that is often accelerated by TGF-? signaling; however, little is known about how the TGF-? pathway is regulated during bone metastasis. Here we report that deleted in liver cancer 1 (DLC1) is an important regulator of TGF-? responses and osteolytic metastasis of breast cancer cells. In murine models, breast cancer cells lacking DLC1 expression exhibited enhanced capabilities of bone metastasis. Knockdown of DLC1 in cancer cells promoted bone metastasis, leading to manifested osteolysis and accelerated death in mice, while DLC1 overexpression suppressed bone metastasis. Activation of Rho-ROCK signaling in the absence of DLC1 mediated SMAD3 linker region phosphorylation and TGF-?–induced expression of parathyroid hormone–like hormone (PTHLH), leading to osteoclast maturation for osteolytic colonization. Furthermore, pharmacological inhibition of Rho-ROCK effectively reduced PTHLH production and breast cancer bone metastasis in vitro and in vivo. Evaluation of clinical breast tumor samples revealed that reduced DLC1 expression was linked to elevated PTHLH expression and organ-specific metastasis to bone. Overall, our findings define a stroma-dependent paradigm of Rho signaling in cancer and implicate Rho–TGF-? crosstalk in osteolytic bone metastasis. PMID:24590291

Wang, Yufeng; Lei, Rong; Zhuang, Xueqian; Zhang, Ning; Pan, Hong; Li, Gang; Hu, Jing; Pan, Xiaoqi; Tao, Qian; Fu, Da; Xiao, Jianru; Chin, Y. Eugene; Kang, Yibin; Yang, Qifeng; Hu, Guohong

2014-01-01

76

Parathyroid hormone may maintain bone formation in hibernating black bears (Ursus americanus) to prevent disuse osteoporosis.  

PubMed

Mechanical unloading of bone causes an imbalance in bone formation and resorption leading to bone loss and increased fracture risk. Black bears (Ursus americanus) are inactive for up to six months during hibernation, yet bone mineral content and strength do not decrease with disuse or aging. To test whether hibernating bears have biological mechanisms to prevent disuse osteoporosis, we measured the serum concentrations of hormones and growth factors involved in bone metabolism and correlated them with the serum concentration of a bone formation marker (osteocalcin). Serum was obtained from black bears over a 7-month duration that included periods of activity and inactivity. Both resorption and formation markers increased during hibernation, suggesting high bone turnover occurred during inactivity. However, bone formation appeared to be balanced with bone resorption. The serum concentration of parathyroid hormone (PTH) was higher in the hibernation (P=0.35) and post-hibernation (P=0.006) seasons relative to pre-hibernation levels. Serum leptin was lower (P<0.004) post-hibernation relative to pre-hibernation and hibernation periods. Insulin-like growth factor I (IGF-I) decreased (P<0.0001) during hibernation relative to pre-hibernation and reached its highest value during remobilization. There was no difference (P=0.64) in 25-OH vitamin D between the three seasons. Serum osteocalcin (bone formation marker) was significantly correlated with PTH, but not with leptin, IGF-I or 25-OH vitamin D. Osteocalcin and PTH were positively correlated when samples from all seasons were pooled and when only hibernation samples were considered, raising the possibility that the anabolic actions of PTH help maintain bone formation to prevent disuse osteoporosis. Prostaglandin E(2) (PGE(2)) release from MC3T3 osteoblastic cells was significantly affected by treatment with bear serum from different seasons (i.e. hibernation versus active periods). The seasonal changes in PGE(2) release showed trends similar to the seasonal changes in serum IGF-I. Since both PGE(2) and IGF-I are associated with collagenous bone formation, it is possible that seasonal changes in a circulating factor influence IGF-I levels in vivo in bears and PGE(2) release in osteoblastic cells in vitro. The significant decrease in serum leptin following arousal from hibernation may promote bone formation during remobilization, assuming there is a similar decrease in intracerebroventricular leptin. These findings support the idea that seasonal changes in the concentration of circulating molecules help regulate bone formation activity and may be important for preventing disuse osteoporosis in bears. PMID:16621944

Donahue, Seth W; Galley, Sarah A; Vaughan, Michael R; Patterson-Buckendahl, Patricia; Demers, Laurence M; Vance, Josef L; McGee, Meghan E

2006-05-01

77

Is serum phosphorus control related to parathyroid hormone control in dialysis patients with secondary hyperparathyroidism?  

PubMed Central

Background Elevated serum phosphorus (P) levels have been linked to increased morbidity and mortality in dialysis patients with secondary hyperparathyroidism (SHPT) but may be difficult to control if parathyroid hormone (PTH) is persistently elevated. We conducted a post hoc analysis of data from an earlier interventional study (OPTIMA) to explore the relationship between PTH control and serum P. Methods The OPTIMA study randomized dialysis patients with intact PTH (iPTH) 300–799?pg/mL to receive conventional care alone (vitamin D and/or phosphate binders [PB]; n?=?184) or a cinacalcet-based regimen (n?=?368). For patients randomized to conventional care, investigators were allowed flexibility in using a non-cinacalcet regimen (with no specific criteria for vitamin D analogue dosage) to attain KDOQI™ targets for iPTH, P, Ca and Ca x P. For those assigned to the cinacalcet-based regimen, dosages of cinacalcet, vitamin D sterols, and PB were optimized over the first 16?weeks of the study, using a predefined treatment algorithm. The present analysis examined achievement of serum P targets (?4.5 and ?5.5?mg/dL) in relation to achievement of iPTH ?300?pg/mL during the efficacy assessment phase (EAP; weeks 17–23). Results Patients who achieved iPTH???300?pg/mL (or a reduction of ?30% from baseline) were more likely to achieve serum P targets than those who did not, regardless of treatment group. Of those who did achieve iPTH???300?pg/mL, 43% achieved P ?4.5?mg/dL and 70% achieved P ?5.5?mg/dL, versus 21% and 46% of those who did not achieve iPTH???300?pg/mL. Doses of PB tended to be higher in patients not achieving serum P targets. Patients receiving cinacalcet were more likely to achieve iPTH ?300?pg/mL than those receiving conventional care (73% vs 23% of patients). Logistic regression analysis identified lower baseline P, no PB use at baseline and cinacalcet treatment to be predictors of achieving P ?4.5?mg/dL during EAP in patients above this threshold at baseline. Conclusions This post hoc analysis found that control of serum P in dialysis patients was better when serum PTH levels were lowered effectively, regardless of treatment received. Trial registration Clinicaltrials.gov identifier NCT00110890 PMID:22863242

2012-01-01

78

Serum Levels of Parathyroid Hormone and Parathyroid?related Peptide in Psoriasis  

Microsoft Academic Search

Psoriasis is a common skin disorder that may be triggered by hormonal disturbances, among other factors. Some studies have demonstrated an elevation of serum para- thyroid hormone (PTH) levels in psoriasis and several other diseases of keratinization of unknown aetiology. PTH-related peptide (PTH-rp), on the other hand, is a potent inhibitor of epidermal cell growth factor and is not expressed

Manuel Sánchez Regaña; Gemma Martín Ezquerra; Pablo Umbert Millet

2005-01-01

79

RenaGel®, a nonabsorbed calcium- and aluminum-free phosphate binder, lowers serum phosphorus and parathyroid hormone  

Microsoft Academic Search

RenaGel®, a nonabsorbed calcium- and aluminum-free phosphate binder, lowers serum phosphorus and parathyroid hormone.Background.This multicenter, open-label, dose-titration study assessed the safety and efficacy of RenaGel®, a nonabsorbed calcium- and aluminum-free phosphate binder, in lowering serum phosphorus. Secondary outcomes were its effects on serum intact parathyroid hormone (iPTH) and serum lipids.Methods.Phosphate binders were discontinued during a two-week washout period. Patients whose

EDUARDO A SLATOPOLSKY; STEVEN K BURKE; MAUREEN A DILLON

1999-01-01

80

Elevated serum parathyroid hormone is a cardiovascular risk factor in moderate chronic kidney disease  

Microsoft Academic Search

Introduction  Over 8% of adults in the United States are estimated to have moderate (stages 3 and 4) chronic kidney disease (CKD), which\\u000a is increasingly recognized as one of the independent predictors for cardiovascular (CV) disease and related mortality. Secondary\\u000a hyperparathyroidism with elevated serum intact parathyroid hormone (iPTH) is associated with increased CV mortality in end-stage\\u000a renal disease and this relationship

Anton Lishmanov; Smrita Dorairajan; Youngju Pak; Kunal Chaudhary; Anand Chockalingam

81

Parathyroid Hormone-Related Protein Purified from a Human Lung Cancer Cell Line  

Microsoft Academic Search

A protein with biological activities similar to parathyroid hormone (PTH) has been purified from serum-free culture medium obtained from a human lung cancer cell line (BEN). A major protein band of 18 kDa was obtained on NaDodSO4\\/polyacrylamide gels, with faint bands at 35 kDa and 67 kDa. Biological activity was associated only with the 18-kDa band. Amino acid sequence analysis

J. M. Moseley; M. Kubota; H. Diefenbach-Jagger; R. E. H. Wettenhall; B. E. Kemp; C. P. Rodda; P. R. Ebeling; P. J. Hudson; J. D. Zajac; T. J. Martin

1987-01-01

82

Serum parathyroid hormone level is associated with body mass index. The 5th Tromso study  

Microsoft Academic Search

Objective: To study whether serum parathyroid hormone (PTH) and serum calcium are associated with body mass index (BMI), and their predicting role in obesity. Design: Population based, cross-sectional study. Methods: In 2001 a population-based health survey was held in Tromsø, North Norway. Question- naires on medical history and life-style factors were completed and anthropometric data were col- lected. Calcium and

Elena Kamycheva; Johan Sundsfjord; Rolf Jorde

2004-01-01

83

Parathyroid hormone-related peptide gene is expressed in the mammalian central nervous system.  

PubMed Central

A parathyroid hormone-related peptide (PTHRP) has been identified in human tumors associated with the syndrome of humoral hypercalcemia of malignancy. While parathyroid hormone (PTH) gene expression appears to be limited to the parathyroid glands, PTHRP mRNA has been identified in a variety of normal tissues. To investigate the apparent expression of the PTHRP in the central nervous system, we examined extracts of whole rat brain for PTHRP bioactivity by measuring adenylate cyclase-stimulating activity (ACSA) in a PTH-sensitive assay. Extracts consistently contained ACSA and this activity was completely inhibited by a PTHRP antiserum but was unaffected by a PTH antiserum. ACSA was found in a number of anatomic subregions of rat brain, being greatest in the cortex and telencephalon. RNase protection analysis revealed PTHRP transcripts in total RNA prepared from whole rat brain and from the same anatomic subregions. By in situ hybridization histochemistry, we found that the highest levels of PTHRP gene expression occurred in neurons of the cerebral cortex, hippocampus, and cerebellar cortex. These studies demonstrate that both PTHRP mRNA and biological activity are present in a number of regions of rat brain. The widespread expression of this peptide by multiple types of neurons suggests that the PTHRP may play a general role in neuronal physiology. Images PMID:2153281

Weir, E C; Brines, M L; Ikeda, K; Burtis, W J; Broadus, A E; Robbins, R J

1990-01-01

84

PFOA and PFOS are associated with reduced expression of the parathyroid hormone 2 receptor (PTH2R) gene in women.  

PubMed

Little is known about interactions between environmental and genetic risk factors for osteoarthritis (OA). Genetic factors include variation or mutation in genes involved in parathyroid hormone signalling. Exposure to the endocrine disrupting chemicals perfluoro-octanoic acid (PFOA) or perfluorooctane sulfonate (PFOS) have been suggested as potential environmental contributors, although evidence to support this association is conflicting. Here we test the hypothesis that PFOA and PFOS may alter the mRNA expression of genes in the parathyroid signalling cascade to provide evidence on possible pathways between these chemicals and OA. We measured the relationship between PFOA or PFOS serum levels and the in vivo expression of the Parathyroid hormone 1 and 2 genes (PTH, PTH2), Parathyroid hormone 1 and 2 receptor genes (PTH1R, PTH2R) and the parathyroid hormone-like (PTHLH) gene in peripheral blood from a cross-sectional population study designed to assess the potential health effects of these chemicals. We used multivariate linear regression models and found that PFOA or PFOS was inversely correlated with parathyroid hormone 2 receptor (PTH2R) expression (coefficients=-0.43 and -0.32, p=p=0.017 and 0.006 for PFOA and PFOS respectively) in 189 female subjects. The levels of PTH2 transcripts encoding the ligand of PTH2r, were also found to be lower in women with OA (median 2.08) compared with controls (median 3.41, p=0.046). As the parathyroid signalling cascade is a known candidate for osteoarthritis risk and our findings raise the possibility that exposure to these chemicals may contribute to the pathogenesis of OA in some individuals. PMID:25462297

Galloway, Tamara S; Fletcher, Tony; Thomas, Oliver J; Lee, Ben P; Pilling, Luke C; Harries, Lorna W

2015-02-01

85

Use of pre-operative Tc99m-Sestamibi scintigraphy and intraoperative parathyroid hormone monitoring to eliminate neck exploration in mediastinal parathyroid adenocarcinoma.  

PubMed

A 66-year-old white woman was found to have an elevated serum calcium and parathyroid hormone (PTH) on routine health evaluation. Physical examination was unremarkable as was ultrasonography of the neck. A sestamibi parathyroid scan revealed abnormal uptake in the anterior mediastinum. Computed tomography of the chest demonstrated an anterior mediastinal mass compatible with a parathyroid adenoma but no neck masses. The patient underwent mediastinoscopy that was converted to a median sternotomy to fully access the mass. The mass was completely resected with surrounding thymus gland. Frozen section confirmed that excised tissue was parathyroid gland in origin. An intraoperative PTH obtained 20 minutes after specimen removal showed a decrease of more than 50% from preoperative levels. The strategy for initial surgery for hyperparathyroidism when a sestamibi scan is "positive" in the mediastinum (only) is a point of some controversy. Traditional recommendations have been to "clear the neck" of abnormal parathyroid tissue before undertaking a more morbid sternotomy. Mediastinoscopy was attempted to remove the mediastinal lesion and to avoid a sternotomy. Preoperative Tc99m sestamibi scintigraphy, frozen section histology, and intraoperative PTH monitoring permitted the authors to conclude that neck exploration was unnecessary. PMID:17462212

Damadi, Amir; Harkema, James; Kareti, Rao; Saxe, Andrew

2007-01-01

86

Dimeric Arrangement of the Parathyroid Hormone Receptor and a Structural Mechanism for Ligand-induced Dissociation  

SciTech Connect

The parathyroid hormone receptor (PTH1R) is a class B G protein-coupled receptor that is activated by parathyroid hormone (PTH) and PTH-related protein (PTHrP). Little is known about the oligomeric state of the receptor and its regulation by hormone. The crystal structure of the ligand-free PTH1R extracellular domain (ECD) reveals an unexpected dimer in which the C-terminal segment of both ECD protomers forms an {alpha}-helix that mimics PTH/PTHrP by occupying the peptide binding groove of the opposing protomer. ECD-mediated oligomerization of intact PTH1R was confirmed in living cells by bioluminescence and fluorescence resonance energy transfer experiments. As predicted by the structure, PTH binding disrupted receptor oligomerization. A receptor rendered monomeric by mutations in the ECD retained wild-type PTH binding and cAMP signaling ability. Our results are consistent with the hypothesis that PTH1R forms constitutive dimers that are dissociated by ligand binding and that monomeric PTH1R is capable of activating G protein.

Pioszak, Augen A.; Harikumar, Kaleeckal G.; Parker, Naomi R.; Miller, Laurence J.; Xu, H. Eric (Van Andel); (Mayo)

2010-06-25

87

Molecular recognition of parathyroid hormone by its G protein-coupled receptor  

SciTech Connect

Parathyroid hormone (PTH) is central to calcium homeostasis and bone maintenance in vertebrates, and as such it has been used for treating osteoporosis. It acts primarily by binding to its receptor, PTH1R, a member of the class B G protein-coupled receptor (GPCR) family that also includes receptors for glucagon, calcitonin, and other therapeutically important peptide hormones. Despite considerable interest and much research, determining the structure of the receptor-hormone complex has been hindered by difficulties in purifying the receptor and obtaining diffraction-quality crystals. Here, we present a method for expression and purification of the extracellular domain (ECD) of human PTH1R engineered as a maltose-binding protein (MBP) fusion that readily crystallizes. The 1.95-{angstrom} structure of PTH bound to the MBP-PTH1R-ECD fusion reveals that PTH docks as an amphipathic helix into a central hydrophobic groove formed by a three-layer {alpha}-{beta}-{beta}{alpha} fold of the PTH1R ECD, resembling a hot dog in a bun. Conservation in the ECD scaffold and the helical structure of peptide hormones emphasizes this hot dog model as a general mechanism of hormone recognition common to class B GPCRs. Our findings reveal critical insights into PTH actions and provide a rational template for drug design that targets this hormone signaling pathway.

Pioszak, Augen A.; Xu, H. Eric (Van Andel)

2008-08-07

88

Probing the bimolecular interactions of parathyroid hormone and the human parathyroid hormone/parathyroid hormone-related protein receptor. 2. Cloning, characterization, and photoaffinity labeling of the recombinant human receptor.  

PubMed

Parathyroid hormone (PTH) acts to regulate calcium homeostasis by interacting with a G-protein-coupled receptor that also binds PTH-related protein (PTHrP). In this report we describe the cloning, characterization, and biological activity of the cloned human (h) PTH/PTHrP receptor (Rc) and cross-linking of a benzophenone-substituted PTH analog, [Nle8,18,Lys13(epsilon-pBZ2),L-2-Nal23,Tyr34]bPTH(1-34 )NH2(K13), to cells endogenously expressing the Rc and cells transiently or stably transfected with the human Rc. A full-length cDNA clone was isolated and fully sequenced from a human kidney cDNA library. Northern blot analysis of normal human tissues revealed a limited tissue distribution: a single transcript of approximately 2.3 kb was detected in kidney, lung, placenta, and liver. In human embryonic kidney cells (HEK-293, clone C-21) stably transfected with hPTH/PTHrP Rc, a single 85-90 kDa Rc-hormone complex was formed after photolysis in the presence of K13. This covalent cross-linking reaction was specifically inhibited by excess quantities of biologically active 1-34 analogs of bovine (b) PTH or hPTHrP but not by C-terminal and midregion PTH peptides. Photoincorporation of 125I-labeled K13 into the Rc occurred with high efficiency (60-70%), approximately an order of magnitude greater than that achieved with conventional aryl azide cross-linking reagents. These results support the feasibility of our approach for specifically cross-linking a tagged PTH analog to the Rc, as a first step in the effort to identify directly the amino acid residues that constitute the Rc binding site. PMID:7654711

Adams, A E; Pines, M; Nakamoto, C; Behar, V; Yang, Q M; Bessalle, R; Chorev, M; Rosenblatt, M; Levine, M A; Suva, L J

1995-08-22

89

Direct mapping of an agonist-binding domain within the parathyroid hormone/parathyroid hormone-related protein receptor by photoaffinity?crosslinking  

PubMed Central

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) are calciotropic hormones interacting with a shared seven-transmembrane domain G protein-coupled receptor, which is located predominantly in bone and kidney. To map the interface of the bimolecular interaction between hormone and receptor, we designed and radioiodinated a bioactive, photoreactive PTH agonist, 125I-[Nle8,18,Lys13(?-p-(3-I-Bz)Bz),l-2-Nal23,Arg26,27,Tyr34]bPTH-(1–34)NH2 (125I-all-R-K13). This ligand contains a photoreactive benzophenone moiety attached to the side chain of Lys13. All other lysyl residues are substituted by argynyls. The analog photocrosslinks specifically to the recombinant hPTH/PTHrP receptor stably transfected into human embryonic kidney cells (HEK-293/C-21 cells, ?400,000 receptors per cell), generating a diffuse ?87-kDa band on SDS/PAGE autoradiography. To identify the “contact domain” within the hPTH/PTHrP receptor involved in binding of 125I-all-R-K13, the radiolabeled band containing the ligand–receptor conjugate was subjected to chemical and enzymatic cleavage. Two independent pathways of sequential digestion were used: Route A, lysyl endopeptidase C, then endo-N-glycosidase F, followed by cyanogen bromide; Route B, cyanogen bromide followed by endo-N-glycosydase F. The identified domain is in contact with position 13 in 125I-all-R-K13 and corresponds to amino acids 173–189 of the hPTH/PTHrP receptor, located at the C-terminal region of the N-terminal extracellular domain. PMID:9108031

Zhou, Alice T.; Bessalle, Roberto; Bisello, Alessandro; Nakamoto, Chizu; Rosenblatt, Michael; Suva, Larry J.; Chorev, Michael

1997-01-01

90

Cinacalcet Effectively Reduces Parathyroid Hormone Secretion and Gland Volume Regardless of Pretreatment Gland Size in Patients with Secondary Hyperparathyroidism  

PubMed Central

Background and objectives: Cinacalcet is effective in reducing serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism. However, it has not been proven whether parathyroid gland size predicts response to therapy and whether cinacalcet is capable of inducing a reduction in parathyroid volume. Design, setting, participants, & measurements: This 52-week, multicenter, open-label study enrolled hemodialysis patients with moderate to severe secondary hyperparathyroidism (intact PTH >300 pg/ml). Doses of cinacalcet were adjusted between 25 and 100 mg to achieve intact PTH <180 pg/ml. Ultrasonography was performed to measure the parathyroid gland size at baseline, week 26, and week 52. Findings were also compared with those of historical controls. Results: Of the 81 subjects enrolled, 56 had parathyroid glands smaller than 500 mm3 (group S) and 25 had at least one enlarged gland larger than 500 mm3 (group L). Treatment with cinacalcet effectively decreased intact PTH by 55% from baseline in group S and by 58% in group L. A slightly greater proportion of patients in group S versus group L achieved an intact PTH <180 pg/ml (46 versus 32%) and a >30% reduction from baseline (88 versus 78%), but this was not statistically significant. Cinacalcet therapy also resulted in a significant reduction in parathyroid gland volume regardless of pretreatment size, which was in sharp contrast to historical controls (n = 87) where parathyroid gland volume progressively increased with traditional therapy alone. Conclusions: Cinacalcet effectively decreases serum PTH levels and concomitantly reduces parathyroid gland volume, even in patients with marked parathyroid hyperplasia. PMID:20798251

Komaba, Hirotaka; Nakanishi, Shohei; Fujimori, Akira; Tanaka, Motoko; Shin, Jeongsoo; Shibuya, Koji; Nishioka, Masato; Hasegawa, Hirohito; Kurosawa, Takeshi

2010-01-01

91

Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis: a paired biopsy study.  

PubMed

We examined paired iliac crest bone biopsy specimens from patients with osteoporosis before and after treatment with daily injections of 400 U of recombinant, human parathyroid hormone 1-34 [PTH(1-34)]. Two groups of patients were studied. The first group was comprised of 8 men with an average age 49 years. They were treated with PTH for 18 months. The second group was comprised of 8 postmenopausal women with an average age 54 years. They were treated with PTH for 36 months. The women had been and were maintained on hormone replacement therapy for the duration of PTH treatment. Patients were supplemented to obtain an average daily intake of 1500 mg of elemental calcium and 100 IU of vitamin D. The biopsy specimens were subjected to routine histomorphometric analysis and microcomputed tomography (CT). Cancellous bone area was maintained in both groups. Cortical width was maintained in men and significantly increased in women. There was no increase in cortical porosity. There was a significant increase in the width of bone packets on the inner aspect of the cortex in both men and women. This was accompanied by a significant decrease in eroded perimeter on this surface in both groups. Micro-CT confirmed the foregoing changes and, in addition, revealed an increase in connectivity density, a three dimensional (3D) measure of trabecular connectivity in the majority of patients. These findings indicate that daily PTH treatment exerts anabolic action on cortical bone in patients with osteoporosis and also can improve cancellous bone microarchitecture. The results provide a structural basis for the recent demonstration that PTH treatment reduces the incidence of osteoporosis-related fractures. PMID:11585349

Dempster, D W; Cosman, F; Kurland, E S; Zhou, H; Nieves, J; Woelfert, L; Shane, E; Plaveti?, K; Müller, R; Bilezikian, J; Lindsay, R

2001-10-01

92

Relationship between intact 1–84 parathyroid hormone and bone histomorphometric parameters in dialysis patients without aluminum toxicity  

Microsoft Academic Search

With the markedly reduced usage of aluminum salts in renal failure, parathyroid hormone (PTH) has become the major determinant of currently seen bone disease. Clinicians now must consider what PTH level should be sought. Too low a level may lead to the aplastic bone lesion (low turnover bone), and too high a level may cause osteitis fibrosa. Furthermore, conventional normal

Mei Wang; Gavril Hercz; Donald J. Sherrard; Norma A. Maloney; Gino V. Segre; York Pei

1995-01-01

93

Focused Cervical Exploration for Primary Hyperparathyroidism without Intraoperative Parathyroid Hormone Monitoring or Use of the Gamma Probe  

Microsoft Academic Search

Selected patients with primary hyperparathyroidism (pHPT) who have a positive preoperative sestamibi scan can be managed safely and successfully with a focused cervical exploration without either adjuvant intraoperative parathyroid hormone (PTH) monitoring or use of a gamma probe. This article reports a retrospective analysis of a consecutive series of patients surgically treated at a tertiary referral center. From August 1998

Steven R. Jacobson; Jon A. van Heerden; David R. Farley; Clive S. Grant; Geoffrey B. Thompson; Brian P. Mullan; Kathleen J. Curlee

2004-01-01

94

Recovery of Parathyroid Hormone Secretion and Function in Postoperative Hypoparathyroidism: A Case Series  

PubMed Central

Context: Transient and permanent postoperative hypoparathyroidism are recognized complications of neck surgery. Postoperative hypoparathyroidism is usually considered permanent when it persists for 6 months; in rare cases, recovery of hypoparathyroidism through 1 year has been described. Recovery of hypoparathyroidism years after diagnosis has not previously been reported. Objective: We report four patients being treated with PTH(1–84) in a research protocol who recovered from postoperative hypoparathyroidism many years after onset. Methods: Recovery from hypoparathyroidism was established by: 1) serum calcium and PTH levels within the normal range off PTH(1–84) treatment for at least 1 week; 2) requirement for daily calcium supplementation reduced to ?1 g; and 3) no supplemental active vitamin D therapy. Results: Hypoparathyroidism developed in three subjects after repeated neck surgery for primary hyperparathyroidism and in one subject after total thyroidectomy for Graves' disease. Parathyroid tissue autotransplant was performed in two of the four subjects. Two had undetectable PTH levels at study entry, whereas the other two subjects had detectable, although low, PTH levels. Hypoparathyroidism had been present for at least 8 years, and in one case for 16 years. The recovery of parathyroid function followed treatment with PTH(1–84) for 36 to 63 months. Conclusions: Although it remains relatively rare, this report documents recovery of long-term postoperative hypoparathyroidism many years after the initial diagnosis. A potential role for exogenous PTH is intriguing with several plausible mechanisms. PMID:24037886

Cusano, Natalie E.; Anderson, Laura; Rubin, Mishaela R.; Silva, Barbara C.; Costa, Aline G.; Irani, Dinaz; Sliney, James

2013-01-01

95

Increased Plasma Concentrations of Vitamin D Metabolites and Vitamin D Binding Protein in Women Using Hormonal Contraceptives: A Cross-Sectional Study  

PubMed Central

Use of hormonal contraceptives (HC) may influence total plasma concentrations of vitamin D metabolites. A likely cause is an increased synthesis of vitamin D binding protein (VDBP). Discrepant results are reported on whether the use of HC affects free concentrations of vitamin D metabolites. Aim: In a cross-sectional study, plasma concentrations of vitamin D metabolites, VDBP, and the calculated free vitamin D index in users and non-users of HC were compared and markers of calcium and bone metabolism investigated. Results: 75 Caucasian women aged 25–35 years were included during winter season. Compared with non-users (n = 23), users of HC (n = 52) had significantly higher plasma concentrations of 25-hydroxyvitamin D (25OHD) (median 84 interquartile range: [67-111] vs. 70 [47-83] nmol/L, p = 0.01), 1,25-dihydroxyvitamin D (1,25(OH)2D) (198 [163-241] vs. 158 [123-183] pmol/L, p = 0.01) and VDBP (358 [260-432] vs. 271 [179-302] µg/mL, p < 0.001). However, the calculated free indices (FI-25OHD and FI-1,25(OH)2D) were not significantly different between groups (p > 0.10). There were no significant differences in indices of calcium homeostasis (plasma concentrations of calcium, parathyroid hormone, and calcitonin, p > 0.21) or bone metabolism (plasma bone specific alkaline phosphatase, osteocalcin, and urinary NTX/creatinine ratio) between groups. In conclusion: Use of HC is associated with 13%–25% higher concentrations of total vitamin D metabolites and VDBP. This however is not reflected in indices of calcium or bone metabolism. Use of HC should be considered in the interpretation of plasma concentrations vitamin D metabolites. PMID:24013463

Møller, Ulla K.; við Streym, Susanna; Jensen, Lars T.; Mosekilde, Leif; Schoenmakers, Inez; Nigdikar, Shailja; Rejnmark, Lars

2013-01-01

96

Renal excretion in gull chicks: effect of parathyroid hormone and calcium loading.  

PubMed

Renal clearance experiments were performed on herring gull (Larus argentatus) and great black-backed gull chicks (L. marinus) to test the importance of parathyroid hormone (PTH), parathyroidectomy (PTX), and calcium loading on excretion patterns of sodium, potassium, calcium, and phosphate. PTX reduced the relative clearance of phosphate to near zero within 2 h. Conversely, PTH stimulated net secretion of phosphate within 40 min. Calcium loading caused a drop in phosphate excretion identical to that of PTX, presumably by inhibiting PTH secretion by the parathyroid glands. This also could be reversed by administration of PTH. Serum phosphate values were highest in PTX gulls and lowest in calcium-loaded gulls. The relative clearance of calcium (CCa/CIn) was elevated in calcium-loaded birds. However, CCa/CIn did not change significantly in response to either PTX or PTH in the sham-operated or PTX birds. Serum calcium values were highest in calcium-loaded gulls and lowest in PTX gulls, the reciprocal of the effects on serum phosphate. PMID:3942252

Clark, N B; Mok, L L

1986-01-01

97

Intraoperative parathyroid hormone assay during focused parathyroidectomy: the importance of 20 minutes measurement  

PubMed Central

Background Parathyroid hormone (PTH) monitoring during the surgical procedure can confirm the removal of all hyperfunctioning parathyroid tissue, as the half-life of PTH is approximately 5 min. The commonly applied Irvin criterion is reported to correctly predict post-operative calcium levels in 96-98% of patients. However, the PTH baseline reference concentration is markedly influenced by surgical manipulations during preparation of the affected glands, interindividual variability of the PTH half-life and modifications in the physiological state of the patient during surgery. The aim of this study was to evaluate the possible impact of the measurement of intraoperative PTH 20 minutes after surgery. Methods Between 2003 and 2012, 188 patients underwent a focused parathyroidectomy associated to rapid intraoperative PTH assay monitoring. Blood samples were collected: 1) at pre-incision time, 2) at 10 min after gland excision and 3) at 20 min after excision, if a sufficient reduction of PTH value was not observed. On the bases of the Irvin criterion, an intra-operative PTH drop>50% from the highest either pre-incision or pre-excision level after parathyroid excision was considered a surgical success. Results A >50% decrease of PTH after gland excision compared to the highest pre-excision value occurred in 156/188 patients (83%) within 10 min and in further 12/188 after 20 minutes (6.4%). In the remaining 20 patients (10.6%) values of PTH remained substantially unchanged or decreased less than 50% and for this reason bilateral neck exploration was performed. An additional pathologic parathyroid was removed in 9 cases, a third in one. In the other 10 cases further neck exploration by a standard cervical approach was negative and in four of these persistent postoperative hypercalcemia was demonstrated. The overall operative success was 97.3%. Intraoperative PTH monitoring was accurate in predicting operative success or failure in 96.3% of patients. Conclusions The 20 minutes PTH measurement appears very useful, avoiding unnecessary bilateral exploration and the related risk of complications with only a slight increase of the duration of surgery and of the costs. PTH values decreasing appeared to be influenced by surgical manipulations during minimally invasive parathyroidectomy. PMID:24044556

2013-01-01

98

Modeling of the Parathyroid Hormone Response after Calcium Intake in Healthy Subjects  

PubMed Central

Plasma ionized calcium (Ca2+) concentrations are tightly regulated in the body and maintained within a narrow range; thus it is challenging to quantify calcium absorption under normal physiologic conditions. This study aimed to develop a mechanistic model for the parathyroid hormone (PTH) response after calcium intake and indirectly compare the difference in oral calcium absorption from PTH responses. PTH and Ca2+ concentrations were collected from 24 subjects from a clinical trial performed to evaluate the safety and calcium absorption of Geumjin Thermal Water in comparison with calcium carbonate tablets in healthy subjects. Indirect response models (NONMEM Ver. 7.2.0) were fitted to observed Ca2+ and PTH data, respectively, in a manner that absorbed but unobserved Ca2+ inhibits the secretion of PTH. Without notable changes in Ca2+ levels, PTH responses were modeled and used as a marker for the extent of calcium absorption. PMID:24976761

Ahn, Jae Eun; Jeon, Sangil; Lee, Jongtae; Han, Seunghoon

2014-01-01

99

Development of monoclonal antibodies against parathyroid hormone: genetic control of the immune response to human PTH  

SciTech Connect

Seventeen monocloanl antibodies against the aminoterminal portion of parathyroid hormone (PTH) were generated by using BALB/c mouse for immunization fully biologically active synthetic human PTH-(1-34) and bovine PTH-(1-84) as immunogens, monoclonal antibody methods, and a solid-phase screening assay. Isotypic analysis of these monoclonal antibodies was performed using affinity purified goat antimouse immunoglobulins specific for IgG heavy chains and ..mu..(IgM). All antibodies were IgM as evidenced by 40 times greater than background activity when 25,000 cpm of /sup 125/I-labelled goat anti-mouse IgM was used as second antibody in a radioimmunoassay.

Nussbaum, S.R.; Lin, C.S.; Potts, J.T. Jr.; Rosenthal, A.S.; Rosenblatt, M.

1985-01-01

100

[Teriparatide: human recombinant parathyroid hormone (1-34) as a daily subcutaneous injection].  

PubMed

Teriparatide is a preparation of human parathyroid hormone (PTH) (1-34). It has been approved as an agent for stimulating bone formation in many foreign countries, including Europe and the United States. In Japan, it was approved in July this year. In nonclinical studies, teriparatide was shown to have a unique bone formation-stimulating effect not seen in existing drugs. In domestic and overseas clinical studies, teriparatide was shown to have strong effects in increasing BMD, promoting remodeling of bone microstructure and suppressing the onset of fracture. Furthermore, teriparatide can increase BMD through stimulation of bone formation regardless of the nature of prior treatment or the presence/absence of responses to prior treatment. With these features, teriparatide is expected to serve as a first-line drug for management of patients with osteoporosis at elevated risk for fracture. PMID:21187589

Sowa, Hideaki; Hamaya, Etsuro; Yamamoto, Takanori

2011-01-01

101

Differential effects of intermittent and continuous administration of parathyroid hormone on bone histomorphometry and gene expression  

NASA Technical Reports Server (NTRS)

A mechanism explaining the differential skeletal effects of intermittent and continuous elevation of serum parathyroid hormone (PTH) remains elusive. Intermittent PTH increases bone formation and bone mass and is being investigated as a therapy for osteoporosis. By contrast, chronic hyperparathyroidism results in the metabolic bone disease osteitis fibrosa characterized by osteomalacia, focal bone resorption, and peritrabecular bone marrow fibrosis. Intermittent and continuous PTH have similar effects on the number of osteoblasts and bone-forming activity. Many of the beneficial as well as detrimental effects of the hormone appear to be mediated by osteoblast-derived growth factors. This hypothesis was tested using cDNA microgene arrays to compare gene expression in tibia of rats treated with continuous and pulsatile administration of PTH. These treatments result in differential expression of many genes, including growth factors. One of the genes whose steady-state mRNA levels was increased by continuous but not pulsatile administration was platelet-derived growth factor-A (PDGF-A). Administration of a PDGF-A antagonist greatly reduced bone resorption, osteomalacia, and bone marrow fibrosis in a rat model for hyperparathyroidism, suggesting that PDGF-A is a causative agent for this disease. These findings suggest that profiling changes in gene expression can help identify the metabolic pathways responsible for the skeletal responses to the hormone.

Lotinun, Sutada; Sibonga, Jean D.; Turner, Russell T.

2002-01-01

102

Differential effects of parathyroid hormone fragments on collagen gene expression in chondrocytes  

PubMed Central

The effect of parathyroid hormone (PTH) in vivo after secretion by the parathyroid gland is mediated by bioactive fragments of the molecule. To elucidate their possible role in the regulation of cartilage matrix metabolism, the influence of the amino-terminal (NH2-terminal), the central, and the carboxyl-terminal (COOH-terminal) portion of the PTH on collagen gene expression was studied in a serum free cell culture system of fetal bovine and human chondrocytes. Expression of alpha1 (I), alpha1 (II), alpha1 (III), and alpha1 (X) mRNA was investigated by in situ hybridization and quantified by Northern blot analysis. NH2- terminal and mid-regional fragments containing a core sequence between amino acid residues 28-34 of PTH induced a significant rise in alpha1 (II) mRNA in proliferating chondrocytes. In addition, the COOH-terminal portion (aa 52-84) of the PTH molecule was shown to exert a stimulatory effect on alpha1 (II) and alpha1 (X) mRNA expression in chondrocytes from the hypertrophic zone of bovine epiphyseal cartilage. PTH peptides harboring either the functional domain in the central or COOH-terminal region of PTH can induce cAMP independent Ca2+ signaling in different subsets of chondrocytes as assessed by microfluorometry of Fura-2/AM loaded cells. These results support the hypothesis that different hormonal effects of PTH on cartilage matrix metabolism are exerted by distinct effector domains and depend on the differentiation stage of the target cell. PMID:8922395

1996-01-01

103

Molecular cloning and chromosomal mapping of DNA rearranged with the parathyroid hormone gene in a parathyroid adenoma.  

PubMed Central

Parathyroid adenomas are common benign neoplasms for which no chromosomal defects have been described. We recently found two parathyroid adenomas bearing clonal restriction fragment abnormalities involving the PTH locus, and now show that in one of these tumors: (a) a DNA rearrangement occurred at the PTH locus; (b) the rearrangement separated the PTH gene's 5' flanking region from its coding exons, conceivably placing a newly adjacent gene under the influence of PTH regulatory elements; (c) the DNA that recombined with PTH normally maps to 11q13, the known chromosomal location of several oncogenes and the gene for multiple endocrine neoplasia type I; and (d) the rearrangement was a reciprocal, conservative recombination of the locus on 11q13 (Human Gene Mapping Library assignment D11S287) with PTH (on 11p15). These data provide molecular cytogenetic evidence for the clonal occurrence of a major chromosome 11 aberrancy in this benign parathyroid tumor. The D11S287 clone could prove useful in genetic linkage analyses, in determining precise 11q13 breakpoints in other neoplasms, and in identifying a gene on chromosome 11 that may participate in parathyroid tumor development. Images PMID:2723071

Arnold, A; Kim, H G; Gaz, R D; Eddy, R L; Fukushima, Y; Byers, M G; Shows, T B; Kronenberg, H M

1989-01-01

104

Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: a randomized, double-blind, placebo-controlled trial  

PubMed Central

Background Increasing evidence suggests the bidirectional interplay between parathyroid hormone and aldosterone as an important mechanism behind the increased risk of cardiovascular damage and bone disease observed in primary hyperparathyroidism. Our primary object is to assess the efficacy of the mineralocorticoid receptor-blocker eplerenone to reduce parathyroid hormone secretion in patients with parathyroid hormone excess. Methods/design Overall, 110 adult male and female patients with primary hyperparathyroidism will be randomly assigned to eplerenone (25 mg once daily for 4 weeks and 4 weeks with 50 mg once daily after dose titration] or placebo, over eight weeks. Each participant will undergo detailed clinical assessment, including anthropometric evaluation, 24-h ambulatory arterial blood pressure monitoring, echocardiography, kidney function and detailed laboratory determination of biomarkers of bone metabolism and cardiovascular disease. The study comprises the following exploratory endpoints: mean change from baseline to week eight in (1) parathyroid hormone(1–84) as the primary endpoint and (2) 24-h systolic and diastolic ambulatory blood pressure levels, NT-pro-BNP, biomarkers of bone metabolism, 24-h urinary protein/albumin excretion and echocardiographic parameters reflecting systolic and diastolic function as well as cardiac dimensions, as secondary endpoints. Discussion In view of the reciprocal interaction between aldosterone and parathyroid hormone and the potentially ensuing target organ damage, the EPATH trial is designed to determine whether eplerenone, compared to placebo, will effectively impact on parathyroid hormone secretion and improve cardiovascular, renal and bone health in patients with primary hyperparathyroidism. Trial registration ISRCTN33941607 PMID:22974443

2012-01-01

105

Effect of parathyroid hormone on transport by toad and turtle bladder  

SciTech Connect

The authors recently demonstrated that parathyroid hormone (PTH) inhibited both vasopressin- and cyclic AMP-stimulated water transport in the toad bladder. This was associated with an increase in calcium uptake by isolated epithelial cells. They postulated that PTH exerts its action on H/sub 2/O transport by directly stimulating calcium uptake. The current study was designed to compare the effects of PTH and the calcium ionophore, A23187, on H/sub 2/O and Na transport and H..mu.. secretion in toad and turtle bladders. In toad bladder, PTH and A23187 decreased arginine vasopressin (AVP)-stimulated H/sub 2/O flow and short-circuit current (SCC) after 60 min serosal incubation. In turtle bladder A23187 decreased SCC to 79.3 +/- 3.6% of base line (P < 0.05), and significantly decreased RSCC as well. PTH had no effect on SCC or H/sup +/ secretion in turtle bladders. Both PTH and A23187 increased /sup 45/Ca uptake in toad bladder epithelial cells; only A23187 increased /sup 45/Ca uptake in the turtle bladder. The different action of PTH in these two membranes, compared with that of the calcium ionophore, illustrates the selectivity of PTH on membrane transport. PTH increases calcium uptake and decreases transport only in a hormone-sensitive epithelium, whereas the ionophore works in virtually all living membranes. The mode of action of these two agents to increase calcium uptake is, therefore likely different.

Sabatini, S.; Kurtzman, N.A.

1987-01-01

106

Parathyroid hormone-sensitive adenylate cyclase system in plasma membranes of rat liver  

SciTech Connect

Purified plasma membranes were prepared from normal rat livers. These membranes were unable to degrade parathyroid hormone (PTH), bovine PTH-(1 to 84) (bPTH-(1 to 84)), or bPTH-(1 to 34). The entire molecule bPTH-(1 to 84) caused a marked activation of adenylate cyclase (cAMP production increased over 5-fold), with half-maximal stimulation at 6.9 x 10/sup -8/ M. The amino-terminal fragment bPTH-(1 to 34) was equipotent but gave a smaller maximal cAMP production. The human (h) amino acid sequence, hPTH-(1 to 34) was only weakly effective at a concentration of 10/sup -5/ M. A similar species specificity was shown with crude rat renal cortical membranes. Of a variety of ligands, only glucagon and 10/sup -3/ M F/sup -/ were cyclase activators in these liver plasma membranes. Binding of (/sup 125/I)iodo-bPTH by these membranes was fairly extensive but showed a saturation of binding only at high hormone concentrations (> 10/sup -6/ M). Clearly, cleavage of the intact molecule PTH-(1 to 84) is not required for activation of the adenylate cyclase system of liver membranes. It appears that two rat tissues, liver and kidney, exhibit some species specificity in cyclase activation, i.e. the hPTH-(1 to 34) (Niall sequence) is inactive.

Neuman, W.F.; Schneider, N.

1980-12-01

107

The calcium-sensing receptor is required for normal calcium homeostasis independent of parathyroid hormone  

PubMed Central

The extracellular calcium-sensing receptor (CaR; alternate gene names, CaR or Casr) is a membrane-spanning G protein–coupled receptor. CaR is highly expressed in the parathyroid gland, and is activated by extracellular calcium (Ca2+o). Mice homozygous for null mutations in the CaR gene (CaR–/–) die shortly after birth because of the effects of severe hyperparathyroidism and hypercalcemia. A wide variety of functions have been attributed to CaR. However, the lethal CaR-deficient phenotype has made it difficult to dissect the direct effect of CaR deficiency from the secondary effects of hyperparathyroidism and hypercalcemia. We therefore generated parathyroid hormone–deficient (PTH-deficient) CaR–/– mice (Pth–/–CaR–/–) by intercrossing mice heterozygous for the null CaR allele with mice heterozygous for a null Pth allele. We show that genetic ablation of PTH is sufficient to rescue the lethal CaR–/– phenotype. Pth–/–CaR–/– mice survive to adulthood with no obvious difference in size or appearance relative to control Pth–/– littermates. Histologic examination of most organs did not reveal abnormalities. These Pth–/–CaR–/– mice exhibit a much wider range of values for serum calcium and renal excretion of calcium than we observe in control littermates, despite the absence of any circulating PTH. Thus, CaR is necessary for the fine regulation of serum calcium levels and renal calcium excretion independent of its effect on PTH secretion. PMID:12671051

Kos, Claudine H.; Karaplis, Andrew C.; Peng, Ji-Bin; Hediger, Matthias A.; Goltzman, David; Mohammad, Khalid S.; Guise, Theresa A.; Pollak, Martin R.

2003-01-01

108

The Association between Parathyroid Hormone Levels and the Cardiorenal Metabolic Syndrome in Non-Diabetic Chronic Kidney Disease  

Microsoft Academic Search

Aims: The relationship between parathyroid hormone (PTH) and the cardiorenal metabolic syndrome was examined among non-diabetic persons with chronic kidney disease (CKD). Methods: In a cross-sectional analysis, the relationship between PTH levels and the cardiorenal metabolic syndrome was investigated in 3,215 non-diabetic participants in the National Kidney Foundation-Kidney Early Evaluation Program (KEEP 2.0) found to have CKD (eGFR <60 ml\\/min\\/1.73

Georges Saab; Adam Whaley-Connell; Andrew Bombeck; Manjula Kurella Tamura; Suying Li; Shu-Cheng Chen; Samy I. McFarlane; James R. Sowers; Keith Norris; George L. Bakris; Peter A. McCullough

2011-01-01

109

?-arrestin2 regulates parathyroid hormone effects on a p38 MAPK and NF?B gene expression network in osteoblasts  

Microsoft Academic Search

Interaction of the cytoplasmic adaptor molecule ?-arrestin2 with the activated parathyroid hormone (PTH)\\/PTHrP receptor inhibits G protein mediated signaling and triggers MAPKs signaling. In turn, the effects of both intermittent (i.) and continuous (c.) PTH on bone are altered in ?-arrestin2-deficient (Arrb2?\\/?) mice. To elucidate the expression profile of bone genes responsive to PTH and targeted for regulation by ?-arrestin2,

Estelle N. Bianchi; Serge L. Ferrari

2009-01-01

110

Role of Mitogen-activated Protein Kinases in the Induction of Parathyroid Hormone-related Peptide1  

Microsoft Academic Search

Tumor production of parathyroid hormone-related protein (PTHRP) is responsible for most cases of hypercalcemia of malignancy. The trans- plantable rat Leydig tumor H-500 is known to cause hypercalcemia in rats by the release of abundant PTHRP and to closely reproduce the human syndrome. We have demonstrated recently that Ras oncogene can stimu- late PTHRP gene expression in Fr3T3 fibroblasts in

Fasika Aklilu; Julienne Gladu; David Goltzman; Shafaat A. Rabbani

2000-01-01

111

Electrogenic Na + \\/ HCO 3 - co-transporter-1 is essential for the parathyroid hormone-stimulated intestinal HCO 3 - secretion  

Microsoft Academic Search

Parathyroid hormone (PTH) was recently demonstrated to enhance the HCO3- secretion through the apical anion channel, cystic fibrosis transmembrane conductance regulator (CFTR), but how the HCO3- entered the epithelial cells was not well understood, in part, due to the lack of specific inhibitors of the basolateral HCO3- transporters. Moreover, the function of the PTH-stimulated HCO3- secretion has never been investigated

Narattaphol Charoenphandhu; Suparerk Laohapitakworn; Kamonshanok Kraidith; La-iad Nakkrasae; Prapaporn Jongwattanapisan; Phuntila Tharabenjasin; Nateetip Krishnamra

2011-01-01

112

Low Vitamin D Status is Associated with Increased Titers of Thyroid Stimulating Hormone Receptor Antibodies in Graves' Disease.  

PubMed

Background: Vitamin D deficiency has been reported to link with a variety of autoimmune diseases. However, the relationship between the thyroid autoimmunity in Graves' disease (GD) and vitamin D deficiency is unclear. The goal of this study was to determine whether increased titers of thyroid autoantibodies were associated with vitamin D deficiency in GD patients.Subjects: Seventy patients with GD and seventy matched control subjects were recruited to our study. The levels of 25-hydroxyvitamin D [25(OH)D], calcium, parathyroid hormone (PTH), free triodothyronine (FT3), free thyroxine (FT4) thyroid-stimulating hormone (TSH), thyrotrophin receptor antibody (TRAb), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) in the serum collected from these patients and controls were examined.Results: The levels of 25(OH)D in serum from TRAb positive GD patients were significantly lower than that from healthy controls or TRAb negative patients. However, the levels of PTH in serum were increased in TRAb positive GD patients compared to control subjects. The rates of vitamin D deficiency (defined as serum 25(OH)D<50 nmol/L) in TRAb positive GD patients were significantly higher than that observed in healthy controls or TRAb negative GD patients. The levels of 25(OH)D in serum were inversely correlated with TRAb titers in serum in TRAb positive GD patients. However, our results did not show a correlation between the levels of 25(OH)D and the levels of TPOAb, TGAb, FT3, FT4, and TSH.Conclusion: Low vitamin D status is associated with increased titers of TRAb in Graves' disease, suggesting a possible link between vitamin D status and increased thyroid autoimmunity in GD patients. PMID:25370319

Zhang, Hong; Liang, Lingyun; Xie, Zhongjian

2014-11-01

113

Intermittently Administered Parathyroid Hormone [1–34] Promotes Tendon-Bone Healing in a Rat Model  

PubMed Central

The objective of this study was to investigate whether intermittent administration of parathyroid hormone [1–34] (PTH[1–34]) promotes tendon-bone healing after anterior cruciate ligament (ACL) reconstruction in vivo. A rat model of ACL reconstruction with autograft was established at the left hind leg. Every day, injections of 60 ?g PTH[1–34]/kg subcutaneously were given to the PTH group rats (n = 10) for four weeks, and the controls (n = 10) received saline. The tendon-bone healing process was evaluated by micro-CT, biomechanical test, histological and immunohistochemical analyses. The effects of PTH[1–34] on serum chemistry, bone microarchitecture and expression of the PTH receptor (PTH1R) and osteocalcin were determined. Administration of PTH[1–34] significantly increased serum levels of calcium, alkaline phosphatase (AP), osteocalcin and tartrate-resistant acid phosphatase (TRAP). The expression of PTH1R on both osteocytes and chondrocyte-like cells at the tendon-bone interface was increased in the PTH group. PTH[1–34] also enhanced the thickness and microarchitecture of trabecular bone according to the micro-CT analysis. The results imply that systematically intermittent administration of PTH[1–34] promotes tendon-bone healing at an early stage via up-regulated PTH1R. This method may enable a new strategy for the promotion of tendon-bone healing after ACL reconstruction. PMID:25268612

Bi, Fanggang; Shi, Zhongli; Jiang, Shuai; Guo, Peng; Yan, Shigui

2014-01-01

114

Inhibition of human platelet aggregation by parathyroid hormone. Is cyclic AMP implicated?  

PubMed

Parathyroid hormone (PTH) is a polypeptide which in different in vitro systems raises intracellular cyclic AMP (cAMP) levels via adenyl cyclase activation and stimulates Ca2+ transport across cell membranes. We tested whether, on the basis of this mechanism, PTH would inhibit human platelet aggregation. The latter was tested in vitro by a photometric technique. Platelet aggregation induced by the calcium ionophore A 23187 was inhibited by PTH at concentrations (0.5-3 USP U/ml) similar to those effective in other in vitro systems. Higher concentrations of PTH were required to prevent aggregation initiated by adenosine-5'-diphosphate, arachidonic acid, or platelet-aggregating factor. The terminal synthetic fragment 1-34 b PTH was ineffective against all aggregation stimuli. The antiaggregating effect of PTH was potentiated by verapamil and theophylline and was additive to that of PGI2. However, PTH did not appear to increase platelet cAMP levels and was not counteracted by an inhibitor of platelet adenyl cyclase. It is therefore unlikely that PTH inhibits platelet aggregation through an adenyl cyclase stimulated increase of cAMP. Since PTH levels are markedly increased in uremic plasma, it might contribute to the defective platelet function and the bleeding tendency frequently occurring in uremic patients. PMID:2996352

Benigni, A; Livio, M; Dodesini, P; Schieppati, A; Panigada, M; Mecca, G; de Gaetano, G; Remuzzi, G

1985-01-01

115

Canine renal parathyroid hormone receptor is a glycoprotein: characterization and partial purification  

SciTech Connect

Covalent labeling of the canine renal parathyroid hormone receptor with (/sup 125/I)bPTH(1-34) reveals several major binding components that display characteristic consistent with a physiologically relevant adenylate cyclase linked receptor. Through the use of the specific glycosidases neuraminidase and endoglycosidase F and affinity chromatography on lectin-agarose gels, we show here that the receptor is a glycoprotein that contains several complex N-linked carbohydrate chains consisting of terminal sialic acid and penultimate galactose in a ..beta..1,4 linkage to N-acetyl-D-glucosamine. No high mannose chains or O-linked glycans appear to be present. The peptide molecular weight of the deglycosylated labeled receptor is 62,000 (or 58,000 if the mass of bPTH(1-34) is excluded). The binding of (/sup 125/I)bPTH(1-34) to the receptor is inhibited in a dose-dependent fashion by wheat-germ agglutinin, but not by either succinylated wheat-germ agglutinin or Ricinus communis lectin, suggesting that terminal sialic acid may be involved in agonist binding. A combination of lectin affinity chromatography and immunoaffinity chromatography affords a 200-fold purification of the covalently labeled receptor.

Karpf, D.B.; Arnaud, C.D.; King, K.; Bambino, T.; Winer, J.; Nyiredy, K.; Nissenson, R.A.

1987-12-01

116

Carbonic anhydrase activity of chick osteoclasts is increased by parathyroid hormone  

SciTech Connect

Embryonic chick osteoclasts were harvested, cultured for 18 h, and separated from erythrocytes, and carbonic anhydrase (CA) activity was assayed. Cultures contained 75-85% osteoclasts by acid phosphatase stain. CA activity was also determined after exposure to parathyroid hormone (PTH). Two methods of measurement were used: a {Delta}pH method, which detects the generation of hydrogen ion by carbonic anhydrase, and a mass spectrometric method, which follows the disappearance of {sup 18}O-enriched CO{sub 2}. Unstimulated osteoclasts showed CA activity that was one-third that of erythrocytes but was comparable with macrophges and chondrocytes. Osteoclasts exposed to PTH showed a twofold increase in activity, which occurred after 30 min. Ethoxzolamide (10{sup {minus}8} M) inhibited enzyme activity by 90%. Treatment of osteoclasts with calcitonin did not prevent the PTH-associated increase in CA activity. The doubling of CA activity with PTH stimulation supports the hypothesis that osteoclastic CA is intimately involved in bone resorption.

Silverton, S.F.; Dodgson, S.J.; Fallon, M.D.; Forster, R.E. II (Univ. of Pennsylvania School of Medicine, Philadelphia (USA))

1987-12-01

117

Parathyroid hormone receptor mediates the anti-myeloma effect of proteasome inhibitors.  

PubMed

Clinically significant serum parathyroid hormone (PTH) variations have been reported in multiple myeloma (MM) patients treated with proteasome inhibitors. To elucidate the association between serum PTH variations and proteasome inhibition in MM, the effect of PTH and PTHR1 ligands on the proteasome inhibitors bortezomib and carfilzomib in vitro and in vivo was determined. The MM cell lines ARP1, OC1 and 5TGM1 expressed mRNA and protein encoding PTH receptor 1 (PTHR1). Treatment of 5TGM1 cells with either PTH(1-34), bortezomib or carfilzomib alone dose-dependently inhibited 5TGM1 cell proliferation. However, treatment with the potent PTHR1 antagonist [TYR34]PTH(7-34) (PTH(7-34)) had no significant effect on myeloma cell proliferation and cell viability. In contrast, when used in combination with bortezomib or carfilzomib, PTH(7-34) treatment significantly reduced the bortezomib or carfilzomib-associated decrease in cell proliferation. Treatment of the C57BL/KaLwRij mouse myeloma model with either bortezomib or carfilzomib provided a significantly prolonged survival benefit compared to controls (p=0.04; p=0.01 respectfully). This potent anti-myeloma effect was completely abrogated by concomitant treatment with PTH(7-34). These results suggest an important role of the PTHR1 in the anti-myeloma effect of proteosome inhibition. PMID:24389365

Zangari, Maurizio; Berno, Tamara; Yang, Ye; Zeng, Ming; Xu, Hongwei; Pappas, Lisa; Tricot, Guido; Kamalakar, Archana; Yoon, Donghoon; Suva, Larry J

2014-04-01

118

Serum levels of intact parathyroid hormone is a prognostic indicator of dialyzed patients: the Nishinomiya study.  

PubMed

Patients with chronic kidney disease on dialysis are at higher risk for cardiovascular disease (CVD), which is the greatest cause of mortality. The target range of serum intact parathyroid hormone (iPTH) for prognosis, 60 to 240?pg/mL, was recommended by the Japanese Society for Dialysis Therapy guidelines. To investigate the impact of this iPTH target on CVD, dialysis patients were enrolled. A total 287 participants were observed. At the start of the study, serum iPTH levels, routine laboratory parameters, and certain factors related to CVD were evaluated. A survival analysis (Kaplan-Meier curve) was used. After 10 years of follow-up, 19.2% of patients had CVD. The subjects were divided into three groups according to their iPTH level at baseline based on the target range of 60 to 240?pg/mL: Low, Middle, and High groups. CVD was more common in the High and Low groups compared to the Middle group. A lower risk of CVD was evident in the extended dialysis patients with a range of 60 to 240?pg/mL iPTH. Further studies are needed to evaluate the impact of the iPTH level on poor outcome. PMID:24206349

Hasuike, Yukiko; Oue, Mai; Hamahata, Sayuri; Kimura, Tomoko; Fukao, Wataru; Mizusaki, Kosuke; Kaibe, Shoji; Nagasawa, Yasuyuki; Kuragano, Takahiro; Nakanishi, Takeshi

2014-08-01

119

Effects of hydrophobic substitutions at position 18 on the potency of parathyroid hormone antagonists.  

PubMed

Position 18 in a parathyroid hormone (PTH) antagonist, [Nle8,18,Tyr34]bPTH(7-34)NH2 (ii), was shown to tolerate substitutions by a range of amino acids with retention of inhibitory activity. The effects of hydrophobic substitutions at this position as a means of enhancing binding interactions with the receptor were evaluated. Substitution of Nle at position 18 with either D-Ala, D-Trp, or L-Trp in analog ii or with Trp (D or L) in the recently reported, highly potent antagonist, [Nle8,18,D-Trp12,Tyr34]bPTH(7-34)NH2 (in vitro activities; Kb = 15 nM and Ki = 125 nM), was performed. In terms of activity on renal receptors, one antagonist, [Nle8,D-Trp12,18,Tyr34]bPTH(7-34)NH2, is the most active in vitro PTH antagonist yet reported (Kb = 4 nM; Ki = 30 nM). The rationale for design of this antagonist and the conclusions regarding PTH-receptor interactions are discussed. PMID:2177456

Chorev, M; Roubini, E; Goldman, M E; McKee, R L; Gibbons, S W; Reagan, J E; Caulfield, M P; Rosenblatt, M

1990-11-01

120

Parathyroid hormone modulates the response of osteoblast-like cells to mechanical stimulation  

NASA Technical Reports Server (NTRS)

Mechanical loading stimulates many responses in bone and osteoblasts associated with osteogenesis. Since loading and parathyroid hormone (PTH) activate similar signaling pathways in osteoblasts, we postulate that PTH can potentiate the effects of mechanical stimulation. Using an in vitro four-point bending device, we found that expression of COX-2, the inducible isoform of cyclooxygenase, was dependent on fluid forces generated across the culture plate, but not physiologic levels of strain in MC3T3-E1 osteoblast-like cells. Addition of 50 nM PTH during loading increased COX-2 expression at both subthreshold and threshold levels of fluid forces compared with either stimuli alone. We also demonstrated that application of fluid shear to MC3T3-E1 cells induced a rapid increase in [Ca(2+)](i). Although PTH did not significantly change [Ca(2+)](i) levels, flow and PTH did produce a significantly greater [Ca(2+)](i) response and increased the number of responding cells than is found in fluid shear alone. The [Ca(2+)](i) response to these stimuli was significantly decreased when the mechanosensitive channel inhibitor, gadolinium, was present. These studies indicate that PTH increases the cellular responses of osteoblasts to mechanical loading. Furthermore, this response may be mediated by alterations in [Ca(2+)](i) by modulating the mechanosensitive channel.

Ryder, K. D.; Duncan, R. L.

2000-01-01

121

Regional responsiveness of the tibia to intermittent administration of parathyroid hormone as affected by skeletal unloading  

NASA Technical Reports Server (NTRS)

To determine whether the acute inhibition of bone formation and deficit in bone mineral induced by skeletal unloading can be prevented, we studied the effects of intermittent parathyroid hormone (PTH) administration (8 micrograms/100 g/day) on growing rats submitted to 8 days of skeletal unloading. Loss of weight bearing decreased periosteal bone formation by 34 and 51% at the tibiofibular junction and tibial midshaft, respectively, and reduced the normal gain in tibial mass by 35%. Treatment with PTH of normally loaded and unloaded animals increased mRNA for osteocalcin (+58 and +148%, respectively), cancellous bone volume in the proximal tibia (+41 and +42%, respectively), and bone formation at the tibiofibular junction (+27 and +27%, respectively). Formation was also stimulated at the midshaft in unloaded (+47%, p < 0.05), but not loaded animals (-3%, NS). Although cancellous bone volume was preserved in PTH-treated, unloaded animals, PTH did not restore periosteal bone formation to normal nor prevent the deficit in overall tibial mass induced by unloading. We conclude that the effects of PTH on bone formation are region specific and load dependent. PTH can prevent the decrease in cancellous bone volume and reduce the decrement in cortical bone formation induced by loss of weight bearing.

Halloran, B. P.; Bikle, D. D.; Harris, J.; Tanner, S.; Curren, T.; Morey-Holton, E.

1997-01-01

122

Proteoglycan 4, a Novel Immunomodulatory Factor, Regulates Parathyroid Hormone Actions on Hematopoietic Cells  

PubMed Central

Proteoglycan 4 (PRG4), a critical protective factor in articular joints, is implicated in hematopoietic progenitor cell expansion and megakaryopoiesis. PRG4 loss-of-function mutations result in camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome, which is characterized primarily by precocious joint failure. PRG4 was identified as a novel parathyroid hormone (PTH) responsiveness gene in osteoblastic cells in bone, and was investigated as a potential mediator of PTH actions on hematopoiesis. Sixteen-week-old Prg4?/? mutant and Prg4+/+ wild-type mice were treated daily with intermittent PTH (residues 1–34) or vehicle for 6 weeks. At 22 weeks of age, Prg4 mutant mice had increased peripheral blood neutrophils and decreased marrow B220+ (B-lymphocytic) cells, which were normalized by PTH. The PTH-induced increase in marrow Lin?Sca-1+c-Kit+ (hematopoietic progenitor) cells was blunted in mutant mice. Basal and PTH-stimulated stromal cell-derived factor-1 (SDF-1) was decreased in mutant mice, suggesting SDF-1 as a candidate regulator of proteoglycan 4 actions on hematopoiesis in vivo. PTH stimulation of IL-6 mRNA was greater in mutant than in wild-type calvaria and bone marrow, suggesting a compensatory mechanism in the PTH-induced increase in marrow hematopoietic progenitor cells. In summary, proteoglycan 4 is a novel PTH-responsive factor regulating immune cells and PTH actions on marrow hematopoietic progenitor cells. PMID:21939632

Novince, Chad M.; Koh, Amy J.; Michalski, Megan N.; Marchesan, Julie T.; Wang, Jason; Jung, Younghun; Berry, Janice E.; Eber, Matthew R.; Rosol, Thomas J.; Taichman, Russell S.; McCauley, Laurie K.

2011-01-01

123

The Impact of Proteoglycan-4 and Parathyroid Hormone on Articular Cartilage  

PubMed Central

Proteoglycan-4 (Prg4) protects synovial joints from arthropathic changes by mechanisms that are incompletely understood. Parathyroid hormone (PTH), known for its anabolic actions in bone, increases Prg4 expression and has been reported to inhibit articular cartilage degeneration in arthropathic joints. To investigate the effect of Prg4 and PTH on articular cartilage, 16-week-old Prg4 mutant and wildtype mice were treated with intermittent PTH (1–34) or vehicle control daily for six weeks. Analyses included histology of the knee joint, micro-CT of the distal femur, and serum biochemical analysis of type II collagen fragments (CTX-II). Compared to wildtype littermates, Prg4 mutant mice had an acellular layer of material lining the surfaces of the articular cartilage and menisci, increased articular cartilage degradation, increased serum CTX-II concentrations, decreased articular chondrocyte apoptosis, increased synovium SDF-1 expression, and irregularly contoured subchondral bone. PTH-treated Prg4 mutant mice developed a secondary deposit overlaying the acellular layer of material lining the joint surfaces, but PTH-treatment did not alter signs of articular cartilage degeneration in Prg4 mutant mice. The increased joint SDF-1 levels and irregular subchondral bone found in Prg4 mutant mice introduce novel candidate mechanisms by which Prg4 protects articular cartilage. PMID:22898906

Novince, Chad M.; Entezami, Payam; Wilson, Christopher G.; Wang, Jason; Oh, Seo; Koh, Amy J.; Michalski, Megan N.; Sinder, Benjamin P.; Kozloff, Kenneth M.; Taichman, Russell S.; McCauley, Laurie K.

2012-01-01

124

Deficiency of the calcium-sensing receptor in the kidney causes parathyroid hormone-independent hypocalciuria.  

PubMed

Rare loss-of-function mutations in the calcium-sensing receptor (Casr) gene lead to decreased urinary calcium excretion in the context of parathyroid hormone (PTH)-dependent hypercalcemia, but the role of Casr in the kidney is unknown. Using animals expressing Cre recombinase driven by the Six2 promoter, we generated mice that appeared grossly normal but had undetectable levels of Casr mRNA and protein in the kidney. Baseline serum calcium, phosphorus, magnesium, and PTH levels were similar to control mice. When challenged with dietary calcium supplementation, however, these mice had significantly lower urinary calcium excretion than controls (urinary calcium to creatinine, 0.31±0.03 versus 0.63±0.14; P=0.001). Western blot analysis on whole-kidney lysates suggested an approximately four-fold increase in activated Na(+)-K(+)-2Cl(-) cotransporter (NKCC2). In addition, experimental animals exhibited significant downregulation of Claudin14, a negative regulator of paracellular cation permeability in the thick ascending limb, and small but significant upregulation of Claudin16, a positive regulator of paracellular cation permeability. Taken together, these data suggest that renal Casr regulates calcium reabsorption in the thick ascending limb, independent of any change in PTH, by increasing the lumen-positive driving force for paracellular Ca(2+) transport. PMID:22997254

Toka, Hakan R; Al-Romaih, Khaldoun; Koshy, Jacob M; DiBartolo, Salvatore; Kos, Claudine H; Quinn, Stephen J; Curhan, Gary C; Mount, David B; Brown, Edward M; Pollak, Martin R

2012-11-01

125

Deficiency of the Calcium-Sensing Receptor in the Kidney Causes Parathyroid Hormone–Independent Hypocalciuria  

PubMed Central

Rare loss-of-function mutations in the calcium-sensing receptor (Casr) gene lead to decreased urinary calcium excretion in the context of parathyroid hormone (PTH)–dependent hypercalcemia, but the role of Casr in the kidney is unknown. Using animals expressing Cre recombinase driven by the Six2 promoter, we generated mice that appeared grossly normal but had undetectable levels of Casr mRNA and protein in the kidney. Baseline serum calcium, phosphorus, magnesium, and PTH levels were similar to control mice. When challenged with dietary calcium supplementation, however, these mice had significantly lower urinary calcium excretion than controls (urinary calcium to creatinine, 0.31±0.03 versus 0.63±0.14; P=0.001). Western blot analysis on whole-kidney lysates suggested an approximately four-fold increase in activated Na+-K+-2Cl? cotransporter (NKCC2). In addition, experimental animals exhibited significant downregulation of Claudin14, a negative regulator of paracellular cation permeability in the thick ascending limb, and small but significant upregulation of Claudin16, a positive regulator of paracellular cation permeability. Taken together, these data suggest that renal Casr regulates calcium reabsorption in the thick ascending limb, independent of any change in PTH, by increasing the lumen-positive driving force for paracellular Ca2+ transport. PMID:22997254

Toka, Hakan R.; Al-Romaih, Khaldoun; Koshy, Jacob M.; DiBartolo, Salvatore; Kos, Claudine H.; Quinn, Stephen J.; Curhan, Gary C.; Mount, David B.; Brown, Edward M.

2012-01-01

126

Parathyroid hormone-related protein (PTHrP) in cartilaginous and bony fish tissues.  

PubMed

Tissues from a range of fish were examined for the presence of parathyroid hormone-related protein (PTHrP) to investigate PTHrP protein distribution and PTHrP gene expression in jawless fish, cartilaginous fish, and bony fish. Immunoreactive PTHrP was localized using antisera to N-terminal and mid-molecule regions of human PTHrP and PTHrP gene expression examined using a digoxigenin labeled riboprobe to a conserved region of the mammalian PTHrP gene. In all of the fish studied, PTHrP protein and messenger RNA (mRNA) were localized to the skin, kidney, and skeletal muscle, following the pattern seen in higher vertebrates. Additional sites of localization for both protein and mRNA included gill, nerve cord, and pituitary, as well as developing dermal denticles and rectal gland in the elasmobranch species. The sites of PTHrP distribution indicate that PTHrP may have roles in ionoregulation as well as growth and differentiation in fish, as has been suggested in higher vertebrates. The results imply that the distribution of PTHrP is widespread in fish and that there is homology between the PTHrP molecules found in humans and fish. The conservation of localization and possible similarity of the PTHrP molecules between tetrapods and fish suggests that PTHrP has a number of fundamental roles in vertebrates. J. Exp. Zool. 284:541-548, 1999. PMID:10469992

Trivett, M K; Officer, R A; Clement, J G; Walker, T I; Joss, J M; Ingleton, P M; Martin, T J; Danks, J A

1999-10-01

127

Parathyroid hormone 1-34 enhances extracellular matrix deposition and organization during flexor tendon repair.  

PubMed

Parathyroid hormone (PTH) 1-34 is known to enhance fracture healing. Tendon repair is analogous to bone healing in its dependence on the proliferation and differentiation of mesenchymal stem cells, matrix formation, and tissue remodeling.(1,2,3) We hypothesized that PTH 1-34 enhances tendon healing in a flexor digitorum longus (FDL) tendon repair model. C57Bl/6J mice were treated with either intraperitoneal PTH 1-34 or vehicle-control (PBS). Tendons were harvested at 3-28 days for histology, gene expression, and biomechanical testing. The metatarsophalangeal joint range of motion was reduced 1.5-2-fold in PTH 1-34 mice compared to control mice. The gliding coefficient, a measure of adhesion formation, was 2-3.5-fold higher in PTH 1-34 mice. At 14 days post-repair, the tensile strength was twofold higher in PTH 1-34 specimens, but at 28 days there were no differences. PTH 1-34 mice had increased fibrous tissue deposition that correlated with elevated expression of collagens and fibronectin as seen on quantitative PCR. PTH 1-34 accelerated the deposition of reparative tissue but increased adhesion formation. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:17-24, 2015. PMID:25266795

Lee, Daniel J; Southgate, Richard D; Farhat, Youssef M; Loiselle, Alayna E; Hammert, Warren C; Awad, Hani A; O'Keefe, Regis J

2015-01-01

128

Impact of parathyroid hormone on bone marrow-derived stem cell mobilization and migration  

PubMed Central

Parathyroid hormone (PTH) is well-known as the principal regulator of calcium homeostasis in the human body and controls bone metabolism via actions on the survival and activation of osteoblasts. The intermittent administration of PTH has been shown to stimulate bone production in mice and men and therefore PTH administration has been recently approved for the treatment of osteoporosis. Besides to its physiological role in bone remodelling PTH has been demonstrated to influence and expand the bone marrow stem cell niche where hematopoietic stem cells, capable of both self-renewal and differentiation, reside. Moreover, intermittent PTH treatment is capable to induce mobilization of progenitor cells from the bone marrow into the bloodstream. This novel function of PTH on modulating the activity of the stem cell niche in the bone marrow as well as on mobilization and regeneration of bone marrow-derived stem cells offers new therapeutic options in bone marrow and stem cell transplantation as well as in the field of ischemic disorders. PMID:25426261

Huber, Bruno C; Grabmaier, Ulrich; Brunner, Stefan

2014-01-01

129

Transcriptional regulation of osteopontin production in rat osteoblast- like cells by parathyroid hormone  

PubMed Central

Osteopontin (OP) or bone sialoprotein is a recently characterized extracellular matrix protein which is abundant in bone and is produced by osteoblasts. Parathyroid hormone (PTH) is a potent calcitropic hormone which regulates osteoblastic function including the synthesis of extracellular matrix proteins. This study examines the effect of human PTH (hPTH-[1-34]) on the expression of this novel protein in rat osteoblast-like cells. hPTH(1-34) significantly decreased the amount of OP in culture media of the rat osteoblastic osteosarcoma cell line, ROS 17/2.8, detected by Western immunoblot analysis. hPTH(1-34) also suppressed the steady-state level of OP mRNA two- to threefold with an ED50 of approximately 3 X 10(-10) M. This inhibition was detectable at 24 h, reached its nadir at 48 h, and lasted at least up to 96 h. The hPTH(1-34) effects were mimicked by isobutylmethylxanthine, cholera toxin, 8-bromo-cAMP, forskolin, and isoproterenol. hPTH(1-34) suppressed by two- to threefold the rate of OP gene transcription, estimated by nuclear run-on assays. The suppression of OP mRNA levels by hPTH(1-34) was also seen when basal levels were increased by transforming growth factor type beta, or 1,25-dihydroxyvitamin D3, or were decreased by dexamethasone. A similar decrease in the steady-state level of OP mRNA by hPTH(1-34) was also observed in primary cultures of osteoblast-enriched cells from fetal rat calvaria. These findings indicate that hPTH(1-34) suppresses the production of the novel extracellular matrix protein, OP, in osteoblasts at least in part through transcriptional control. PMID:2465299

1989-01-01

130

Fundamentals of vitamin D hormone-regulated gene expression.  

PubMed

Initial research focused upon several known genetic targets provided early insight into the mechanism of action of the vitamin D hormone (1,25-dihydroxyvitamin D3 (1,25(OH)2D3)). Recently, however, a series of technical advances involving the coupling of chromatin immunoprecipitation (ChIP) to unbiased methodologies that initially involved tiled DNA microarrays (ChIP-chip analysis) and now Next Generation DNA Sequencing techniques (ChIP-seq analysis) has opened new avenues of research into the mechanisms through which 1,25(OH)2D3 regulates gene expression. In this review, we summarize briefly the results of this early work and then focus on more recent studies in which ChIP-chip and ChIP-seq analyses have been used to explore the mechanisms of 1,25(OH)2D3 action on a genome-wide scale providing specific target genes as examples. The results of this work have advanced our understanding of the mechanisms involved at both genetic and epigenetic levels and have revealed a series of new principles through which the vitamin D hormone functions to control the expression of genes. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. PMID:24239506

Pike, J Wesley; Meyer, Mark B

2014-10-01

131

A 10-Year Experience in Intraoperative Parathyroid Hormone Measurements for Primary Hyperparathyroidism: A Prospective Study of 91 Previous Unexplored Patients  

PubMed Central

Introduction. Primary hyperparathyroidism (PHP) is characteristically determined by high levels of calcium and high or inappropriate levels of parathyroid hormone (PTH). Technological advances have dramatically changed the surgical technique over the years once intraoperative parathyroid hormone (IOPTH) assay had allowed for focused approaches. Objective. To evaluate our 10-year experience in employing a rapid intraoperative PTH assay for PHP. Methods. A prospective cohort of 91 PHP-operated patients in a tertiary institution in São Paulo, Brazil, from June 2000 to April 2011. Results. We had 85 (93.4%) successful parathyroidectomies, 6 (6.6%) failed parathyroidectomies in 91 previous unexplored patients, and 5 (100%) successful remedial surgeries. The IOPTH was true-positive in 88.5%, true-negative in 7.3%, false-positive in 2.1%, and false-negative in 2.1% of the procedures. IOPTH was able to obviate additional exploration or to ask for additional exploration in 92 (95.8%) procedures. Conclusion. The IOPTH revealed to be an important technological adjunct in the current parathyroid surgery for PHP. PMID:22523718

Neves, M. C.; Ohe, M. N.; Rosano, M.; Abrahão, M.; Cervantes, O.; Lazaretti-Castro, M.; Vieira, J. G. H.; Kunii, I. S.; Santos, R. O.

2012-01-01

132

Effects of Different 1-34 Parathyroid Hormone Dosages on Fibroblast Growth Factor-23 Secretion in Human Bone Marrow Cells following Osteogenic Differentiation.  

PubMed

The importance of fibroblast growth factor (FGF)-23 as part of a hormonal bone-kidney-axis has been well established. Lately, FGF-23 has been suggested as an independent risk factor of death in patients on chronic hemodialysis. Hyperparathyroidism is a common feature of advanced kidney failure or end-stage renal disease. The independent effect of elevated parathyroid hormone (PTH) levels on FGF-23 secretion is still a matter of debate and has not yet been studied in an in vitro model of human bone marrow cells (BMC) during osteogenic differentiation. BMC from three different donors were cultivated for 4 weeks in cell cultures devoid of vitamin D either without 1-34 PTH or with PTH concentrations of 10 or 100 pmol/L, respectively. After 28 days, protein expression of the cells was determined by immunocytochemical staining, whereas real time-polymerase chain reaction served to analyze gene expression of several osteoblastic (osteocalcin, RANKL, Runx-2 and ostase) and osteoclastic markers (RANK, TRAP-5b). The concentrations of FGF-23, ostase and TRAP-5b were determined by ELISA at weeks 2, 3 and 4. We found a basal expression of FGF-23 with no increase in FGF-23 secretion after stimulation with 10 pmol/L 1-34 PTH. Stimulation with 100 pmol/L PTH resulted in an increase in FGF-23 expression (14.1±3.6 pg/mL with no PTH, 13.7±4.0 pg/mL with 10 pmol/L, P=0.84 and 17.6±3.4 pg/mL with 100 pmol/L, P=0.047). These results suggest a vitamin D and PTH-independent FGF-23 expression in human BMC after osteogenic stimulation. As only higher PTH levels stimulated FGF-23 expression, a threshold level might be hypothesized. PMID:25002935

Tillmann, Frank-Peter; Hofen, Daniela; Herten, Monika; Krauspe, Rüdiger; Jäger, Marcus

2014-04-22

133

Effects of phosphatidic acid on parathyroid hormone release, intracellular free Ca2+, and inositol phosphates in dispersed bovine parathyroid cells.  

PubMed

The observation that increases in extracellular Ca2+ or the addition of divalent cations, such as Ba2+, Mg2+, Mn2+, or Sr2+, stimulate the accumulation of inositol trisphosphate (InsP3) and its breakdown products in parathyroid cells strongly supports the idea that polyphosphoinositides are hydrolyzed under these conditions. Since phosphatidic acid is produced as a result of polyphosphoinositide hydrolysis, and it has been proposed that phosphatidic acid may be a second messenger for Ca2+ mobilization, we examined the effects of this compound on parathyroid cells. We assessed PTH release, intracellular free Ca2+ ([Ca2+]i), and inositol polyphosphate accumulation in response to phosphatidic acid. Natural phosphatidic acid reduced PTH release at 1.0 mM extracellular Ca2+ by 18 +/- 6%, 48 +/- 5%, 59 +/- 10%, and 79 +/- 6% at concentrations of 1, 10, 50, and 100 micrograms/ml, respectively (n = 5-11). The effect was not dependent on the presence of extracellular Ca2+, since phosphatidic acid (100 micrograms/ml) inhibited PTH secretion by 39 +/- 3% in medium with no added Ca2+ and 1.0 mM EGTA (n = 3). This agent rapidly and transiently increased [Ca2+]i in a dose-dependent manner, as determined by fura-2 fluorescence. At 1.0 mM extracellular Ca2+, [Ca2+]i rose from 309 +/- 8 to a peak of 356 +/- 26, 454 +/- 22, and 587 +/- 57 nM with the addition of 1, 10, and 100 micrograms/ml phosphatidic acid, respectively (n = 2-14). In the absence of extracellular Ca2+ (i.e. medium with 1 or 2 mM EGTA and no added Ca2+), phosphatidic acid produced a quantitatively smaller peak increment of 38 +/- 4% in [Ca2+]i, indicating that this compound could mobilize Ca2+ from intracellular stores (n = 3). At 1.0 mM extracellular Ca2+, phosphatidic acid (200 micrograms/ml) stimulated the accumulation of Inositol trisphosphate (InsP3), Inositol bisphosphate (InsP2), and Inositol monophosphate (InsP1) by 46 +/- 9%, 37 +/- 9%, and 59 +/- 11% after 60 sec, respectively (n = 5-7). Phosphatidic acid had no significant effect on forskolin-stimulated cAMP accumulation. We further determined whether the specific fatty acid composition of phosphatidic acid might influence its effects in parathyroid cells by testing several synthetic compounds. Dipalmitoyl phosphatidic acid (greater than or equal to 50 micrograms/ml) inhibited PTH release in a dose-dependent manner without significantly changing [Ca2+]i. Dioleoyl phosphatidic acid had modest biphasic effects on secretion, with 20 +/- 5% inhibition observed at lower doses (10 micrograms/ml) and a 27 +/- 8% stimulation of secretion at 100 micrograms/ml (n = 6).(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2153532

McGhee, J G; Shoback, D M

1990-02-01

134

Critical role of parathyroid hormone (PTH) receptor-1 phosphorylation in regulating acute responses to PTH  

PubMed Central

Agonist-induced phosphorylation of the parathyroid hormone (PTH) receptor 1 (PTHR1) regulates receptor signaling in vitro, but the role of this phosphorylation in vivo is uncertain. We investigated this role by injecting “knock-in” mice expressing a phosphorylation-deficient (PD) PTHR1 with PTH ligands and assessing acute biologic responses. Following injection with PTH (1–34), or with a unique, long-acting PTH analog, PD mice, compared with WT mice, exhibited enhanced increases in cAMP levels in the blood, as well as enhanced cAMP production and gene expression responses in bone and kidney tissue. Surprisingly, however, the hallmark hypercalcemic and hypophosphatemic responses were markedly absent in the PD mice, such that paradoxical hypocalcemic and hyperphosphatemic responses were observed, quite strikingly with the long-acting PTH analog. Spot urine analyses revealed a marked defect in the capacity of the PD mice to excrete phosphate, as well as cAMP, into the urine in response to PTH injection. This defect in renal excretion was associated with a severe, PTH-induced impairment in glomerular filtration, as assessed by the rate of FITC-inulin clearance from the blood, which, in turn, was explainable by an overly exuberant systemic hypotensive response. The overall findings demonstrate the importance in vivo of PTH-induced phosphorylation of the PTHR1 in regulating acute ligand responses, and they serve to focus attention on mechanisms that underlie the acute calcemic response to PTH and factors, such as blood phosphate levels, that influence it. PMID:23533279

Maeda, Akira; Okazaki, Makoto; Baron, David M.; Dean, Thomas; Khatri, Ashok; Mahon, Mathew; Segawa, Hiroko; Abou-Samra, Abdul B.; Jüppner, Harald; Bloch, Kenneth D.; Potts, John T.; Gardella, Thomas J.

2013-01-01

135

Parathyroid hormone activates the orphan nuclear receptor Nurr1 to induce FGF23 transcription.  

PubMed

Parathyroid hormone (PTH) increases FGF23 mRNA and protein levels in vivo and in vitro. Here we tested whether the increased FGF23 expression by PTH is mediated by the orphan nuclear receptor Nurr1. PTH increased Nurr1 mRNA levels prior to elevation of FGF23 mRNA levels in UMR-106 rat osteoblast-like cells. Activation of PKA increased both FGF23 and Nurr1 mRNA levels. Modification of Nurr1 expression showed that Nurr1 is essential for the PTH-mediated increase in FGF23 and luciferase reporter gene experiments identified a functional promoter region containing several potential Nurr1 binding sites. Chromatin immunoprecipitation assays confirmed the binding of Nurr1 to these regions in the FGF23 promoter. In vivo, Nurr1 mRNA and protein levels were increased in calvaria from rats with experimental CKD together with high PTH and FGF23 expression. Calcimimetics decrease PTH and FGF23 levels in CKD patients. Importantly, in rats with experimental CKD, the calcimimetic R568 decreased PTH expression, calvaria Nurr1 mRNA and protein levels, and FGF23 mRNA. Immunohistochemistry for Nurr1 showed an increase in the number of Nurr1 expressing osteocytes in the femurs of rats with CKD and this was decreased by R568. Thus, the effect of PTH to increase FGF23 transcription is mediated by Nurr1 in vitro and in vivo. In CKD, calcimimetics decrease PTH, which in turn decreases Nurr1 and consequently FGF23. PMID:24940803

Meir, Tomer; Durlacher, Karina; Pan, Zheng; Amir, Gail; Richards, William G; Silver, Justin; Naveh-Many, Tally

2014-12-01

136

Parathyroid hormone induces the Nrna family of nuclear orphan receptors in vivo  

SciTech Connect

Parathyroid hormone (PTH) has both anabolic and catabolic effects on bone metabolism, although the molecular mechanisms mediating these effects are largely unknown. Among the transcription factors induced by Pth in osteoblasts are the nerve growth factor-inducible factor B (NR4A; NGFI-B) family of orphan nuclear receptors: Nurr1, Nur77, and NOR-1. PTH induces NR4A members through the cAMP-protein kinase A (PKA) pathway in vitro. We report here that PTH rapidly and transiently induced expression of all three NR4A genes in PTH-target tissues in vivo. In calvaria, long bones, and kidneys, NR4A induction was maximal 0.5-1 h after a single intraperitoneal (i.p.) injection of 80 {mu}g/kg PTH. Nur77 demonstrated the highest expression, followed, in order, by Nurr1 and NOR-1. In calvaria and long bone, PTH-induced expression of each NR4A gene was detectable at 10 {mu}g/kg i.p. with maximum induction at 40-80 {mu}g/kg. PTH (3-34) did not induce NR4A mRNA levels in calvaria, long bone, and kidney in vivo, confirming our in vitro results that NR4A genes are induced primarily through the cAMP-PKA pathway. The magnitude of PTH-induced NR4A expression was comparable in vivo and in vitro. However, NR4A mRNA levels peaked and returned to baseline faster in vivo. Both in vivo and in vitro, PTH induced NR4A pre-mRNA levels suggesting that induction of these genes is, at least in part, through activation of mRNA synthesis. The in vivo induction of the NR4A family members by PTH suggests their involvement in, at least some, PTH-induced changes in bone metabolism.

Pirih, Flavia Q. [Division of Diagnostic and Surgical Sciences, UCLA School of Dentistry, Los Angeles, CA 90095 (United States)]. E-mail: fqpirih@ucla.edu; Aghaloo, Tara L. [Division of Diagnostic and Surgical Sciences, UCLA School of Dentistry, Los Angeles, CA 90095 (United States)]. E-mail: taghaloo@ucla.edu; Bezouglaia, Olga [Division of Diagnostic and Surgical Sciences, UCLA School of Dentistry, Los Angeles, CA 90095 (United States)]. E-mail: obezougl@ucla.edu; Nervina, Jeanne M. [Section of Orthodontics, UCLA School of Dentistry, Los Angeles, CA 90095 (United States)]. E-mail: jnervina@ucla.edu; Tetradis, Sotirios [Division of Diagnostic and Surgical Sciences, UCLA School of Dentistry, Los Angeles, CA 90095 (United States); UCLA Molecular Biology Institute, Los Angeles, CA 90095 (United States); E-mail: sotirist@dent.ucla.edu

2005-07-01

137

Intact parathyroid hormone levels are associated with increased carotid intima media thickness in HIV infected patients.  

PubMed

Aim. Preliminary evidence suggests that intact parathyroid hormone (iPTH) and bone mineral abnormalities may contribute to the development of vascular disease and are associated with reduced survival in the general population. Whether iPTH is associated with subclinical atherosclerosis in HIV-infected individuals has not been elucidated. Methods. Cross-sectional study of 470 consecutive HIV-infected patients in whom we measured carotid intima-media thickness (cIMT), and collected demographical, clinical and laboratory data. High-cIMT was defined as a mean IMT above the 75th percentile for the study cohort. Parametric, non-parametric tests and logistic regression analyses were used to compare patients' characteristics between low- and high-cIMT and to test the association between high-cIMT and log-transformed iPTH. Results. Of the 470 patients, 130 had high-cIMT. High-cIMT subjects were older and more likely to be male and have a history of cardiovascular disease. Glucose, lipid and iPTH levels were lower among low-cIMT subjects (p < 0.05). Unadjusted and multivariable adjusted analyses demonstrated an independent association between high-cIMT and iPTH (fully adjusted OR: 1.74; 95%CI: 1.08-2.79; p = 0.021). Bootstrap and sensitivity analyses confirmed these findings. Conclusions. Elevated iPTH was associated with subclinical atherosclerosis in HIV-infected subjects. Of note this association was statistically significant even for iPTH values within the range of normality. The existence of a causal relationship between iPTH and atherosclerosis needs to be fully explored in future investigations. PMID:25463096

Bellasi, Antonio; Raggi, Paolo; Rossi, Rosario; Rochira, Vincenzo; Stentarelli, Chiara; Zona, Stefano; Lattanzi, Antonella; Carli, Federica; Mussini, Cristina; Guaraldi, Giovanni

2014-12-01

138

Radioimmunoassay for amino- and carboxyl terminal parathyroid hormone: Its clinical application  

SciTech Connect

It has been well known that the circulating parathyroid hormones are immunochemically heterogenous. The authors have employed the region-specific radioimmunoassays directed against N-PTH using (1-34) human PTH and C-PTH using (65-84) human PTH to evaluate its clinical usefulness. Serum N-PTH and C-PTH levels were measured in 50 normal subjects, 17 primary hyperparathyroidism (1/sup 0/ HPT), 14 hypercalcemia associated with cancer and 30 chronic renal failure (CRF) on dialysis. In 1/sup 0/ HPT, higher N-PTH levels were observed in 6, while higher C-PTH levels in 13. Among 1/sup 0/ HPT, patients with bone type (osteitis fibrosa), compared with stone or chemical type, showed significantly higher N-PTH and C-PTH levels (bone type vs. stone and chemical type; p<0.001 for N-PTH and p<0.01 for C-PTH). Neither N-PTH nor C-PTH assay could be differentiated 1/sup 0/ HPT from hypercalcemia associated with cancer. In CRF, the increased N-PTH levels were observed in 6, while the increased C-PTH levels in 30. Among CRF, patients with osteitis fibrosa showed significantly higher N-PTH and C-PTH (with vs. without osteitis fibrosa; p<0.001 for N-PTH and p<0.025 for C-PTH). In conclusion, each assay has its own value in clinical settings, with the N-PTH assay being used in evaluation of the biological effect of PTH (eg. the recognition of the existence of osteitis fibrosa in 1/sup 0/ HPT and CRF) and the C-PTH assay primarily serving the differential diagnosis of 1/sup 0/ HPT from normal subjects.

Fukunaga, M.; Otsuka, N.; Sone, T.; Muranake, A.; Yanagimoto, S.; Tomomitsu, T.; Morita, R.; Yamamoto, I.; Torizuka, K.; Dokoh, S.

1985-05-01

139

Parathyroid Hormone Related-Protein Promotes Epithelial-to-Mesenchymal Transition in Prostate Cancer  

PubMed Central

Parathyroid hormone-related protein (PTHrP) possesses a variety of physiological and developmental functions and is also known to facilitate the progression of many common cancers, notably their skeletal invasion, primarily by increasing bone resorption. The purpose of this study was to determine whether PTHrP could promote epithelial-to-mesenchymal transition (EMT), a process implicated in cancer stem cells that is critically involved in cancer invasion and metastasis. EMT was observed in DU 145 prostate cancer cells stably overexpressing either the 1-141 or 1-173 isoform of PTHrP, where there was upregulation of Snail and vimentin and downregulation of E-cadherin relative to parental DU 145. By contrast, the opposite effect was observed in PC-3 prostate cancer cells where high levels of PTHrP were knocked-down via lentiviral siRNA transduction. Increased tumor progression was observed in PTHrP-overexpressing DU 145 cells while decreased progression was observed in PTHrP-knockdown PC-3 cells. PTHrP-overexpressing DU 145 formed larger tumors when implanted orthoptopically into nude mice and in one case resulted in spinal metastasis, an effect not observed among mice injected with parental DU 145 cells. PTHrP-overexpressing DU 145 cells also caused significant bone destruction when injected into the tibiae of nude mice, while parental DU 145 cells caused little to no destruction of bone. Together, these results suggest that PTHrP may work through EMT to promote an aggressive and metastatic phenotype in prostate cancer, a pathway of importance in cancer stem cells. Thus, continued efforts to elucidate the pathways involved in PTHrP-induced EMT as well as to develop ways to specifically target PTHrP signaling may lead to more effective therapies for prostate cancer. PMID:24465715

Rahimy, Elham; Yang, Meng; Hoffman, Robert M.; Wang-Rodriguez, Jessica; Deftos, Leonard J.

2014-01-01

140

Proteoglycan 4: A Dynamic Regulator of Skeletogenesis and Parathyroid Hormone Skeletal Anabolism  

PubMed Central

Proteoglycan 4 (Prg4), known for its lubricating and protective actions in joints, is a strong candidate regulator of skeletal homeostasis and parathyroid hormone (PTH) anabolism. Prg4 is a PTH-responsive gene in bone and liver. Prg4 null mutant mice were used to investigate the impact of proteoglycan 4 on skeletal development, remodeling, and PTH anabolic actions. Young Prg4 mutant and wild-type mice were administered intermittent PTH(1–34) or vehicle daily from 4 to 21 days. Young Prg4 mutant mice had decreased growth plate hypertrophic zones, trabecular bone, and serum bone formation markers versus wild-type mice, but responded with a similar anabolic response to PTH. Adult Prg4 mutant and wild-type mice were administered intermittent PTH(1–34) or vehicle daily from 16 to 22 weeks. Adult Prg4 mutant mice had decreased trabecular and cortical bone, and blunted PTH-mediated increases in bone mass. Joint range of motion and animal mobility were lower in adult Prg4 mutant versus wild-type mice. Adult Prg4 mutant mice had decreased marrow and liver fibroblast growth factor 2 (FGF-2) mRNA and reduced serum FGF-2, which were normalized by PTH. A single dose of PTH decreased the PTH/PTHrP receptor (PPR), and increased Prg4 and FGF-2 to a similar extent in liver and bone. Proteoglycan 4 supports endochondral bone formation and the attainment of peak trabecular bone mass, and appears to support skeletal homeostasis indirectly by protecting joint function. Bone- and liver-derived FGF-2 likely regulate proteoglycan 4 actions supporting trabeculae formation. Blunted PTH anabolic responses in adult Prg4 mutant mice are associated with altered biomechanical impact secondary to joint failure. PMID:21932346

Novince, Chad M; Michalski, Megan N; Koh, Amy J; Sinder, Benjamin P; Entezami, Payam; Eber, Matthew R; Pettway, Glenda J; Rosol, Thomas J; Wronski, Thomas J; Kozloff, Ken M; McCauley, Laurie K

2014-01-01

141

G?q Signal in Osteoblasts Is Inhibitory to the Osteoanabolic Action of Parathyroid Hormone*  

PubMed Central

This study examined the role of the G?q signal constituted by G?q and G?11 (encoded by Gn?q and Gn?11, respectively), a major intracellular pathway of parathyroid hormone (PTH), in the PTH osteoanabolic action by the gain- and loss-of-function analyses. Transgenic mice with osteoblast-specific overexpression of the constitutively active Gn?q gene under the control of 2.3-kb type I collagen ?1 chain (Col1a1) promoter exhibited osteopenia with decreased bone formation parameters and did not respond to the daily PTH treatment. We then established osteoblast-specific Gn?q and Gn?11 double-knock-out (cDKO) mice by crossing the 2.3-kb Col1a1 promoter-Cre recombinase transgenic mice and those with Gn?q gene flanked with loxP and global ablation of Gn?11 (Col1a1-Cre+/?;Gnaqfl/fl;Gna11?/?) and found that the cDKO and single knock-out littermates of Gn?q or Gn?11 exhibited normal bone volume and turnover under physiological conditions. With a daily injection of PTH, however, the cDKO mice, but not the single knock-out mice, showed higher bone volume and turnover than the wild-type littermates. Cultures of primary osteoblasts derived from cDKO and wild-type littermates confirmed enhancement of the PTH osteoanabolic action by the G?q signal deficiency in a cell-autonomous mechanism, in association with the membrane translocation of protein kinase C?. This enhancement was reproduced by overexpression of regulator of G protein signaling-2, a G?q signal inhibitor, in osteoblastic MC3T3-E1 cells. Hence, the G?q signal plays an inhibitory role in the PTH osteoanabolic action, suggesting that its suppression may lead to a novel treatment in combination with PTH against osteoporosis. PMID:21345793

Ogata, Naoshi; Shinoda, Yusuke; Wettschureck, Nina; Offermanns, Stefan; Takeda, Shu; Nakamura, Kozo; Segre, Gino V.; Chung, Ung-il; Kawaguchi, Hiroshi

2011-01-01

142

Systemic but No Local Effects of Combined Zoledronate and Parathyroid Hormone Treatment in Experimental Autoimmune Arthritis  

PubMed Central

Introduction Local bone erosions and osteoporosis in rheumatoid arthritis (RA) are the result of a more pronounced bone resorption than bone formation. Present treatment strategies for RA inhibit inflammation, but do not directly target bone erosions. The aim of the study was in experimental arthritis to investigate the juxtaarticular and systemic effects of simultaneous osteoclast inhibition with zoledronate (ZLN) and osteoblast stimulation with parathyroid hormone (PTH). Methods Arthritis was induced in 36 SKG mice. The mice were randomized to three treatment groups and an untreated group: ZLN, PTH, PTH+ZLN, and untreated. Arthritis score and ankle width measurements were performed. Histological sections were cut from the right hind paw, and design-based stereological estimators were used to quantify histological variables of bone volume and bone formation and resorption. The femora were DXA- and ?CT-scanned, and the bone strength was determined at the femoral neck and mid-diaphysis. Results Locally, we found no differences in arthritis score or ankle width throughout the study. Similarly, none of the treatments inhibited bone erosions or stimulated bone formation in the paw. Systemically, all treatments improved bone mineral density, strength of the femoral neck and mid-diaphysis, and ?CT parameters of both cortical and trabecular bone. In addition, there was an additive effect of combination treatment compared with single treatments for most trabecular parameters including bone mineral density and bone volume fraction. Conclusions No local effect on bone was found by the combined action of inhibiting bone resorption and stimulating bone formation. However, a clear systemic effect of the combination treatment was demonstrated. PMID:24637846

Keller, Kresten Krarup; Thomsen, Jesper Skovhus; Stengaard-Pedersen, Kristian; Hauge, Ellen-Margrethe

2014-01-01

143

Role of paraoxonase-1 in bone anabolic effects of parathyroid hormone in hyperlipidemic mice  

SciTech Connect

Highlights: ? Anabolic effects of PTH were tested in hyperlipidemic mice overexpressing PON1. ? Expression of antioxidant regulatory genes was induced in PON1 overexpression. ? Bone resorptive activity was reduced in PON1 overexpressing hyperlipidemic mice. ? PON1 restored responsiveness to intermittent PTH in bones of hyperlipidemic mice. -- Abstract: Hyperlipidemia blunts anabolic effects of intermittent parathyroid hormone (PTH) on cortical bone, and the responsiveness to PTH are restored in part by oral administration of the antioxidant ApoA-I mimetic peptide, D-4F. To evaluate the mechanism of this rescue, hyperlipidemic mice overexpressing the high-density lipoprotein-associated antioxidant enzyme, paraoxonase 1 (Ldlr{sup ?/?}PON1{sup tg}) were generated, and daily PTH injections were administered to Ldlr{sup ?/?}PON1{sup tg} and to littermate Ldlr{sup ?/?} mice. Expression of bone regulatory genes was determined by realtime RT-qPCR, and cortical bone parameters of the femoral bones by micro-computed tomographic analyses. PTH-treated Ldlr{sup ?/?}PON1{sup tg} mice had significantly greater expression of PTH receptor (PTH1R), activating transcription factor-4 (ATF4), and osteoprotegerin (OPG) in femoral cortical bone, as well as significantly greater cortical bone mineral content, thickness, and area in femoral diaphyses compared with untreated Ldlr{sup ?/?}PON1{sup tg} mice. In contrast, in control mice (Ldlr{sup ?/?}) without PON1 overexpression, PTH treatment did not induce these markers. Calvarial bone of PTH-treated Ldlr{sup ?/?}PON1{sup tg} mice also had significantly greater expression of osteoblastic differentiation marker genes as well as BMP-2-target and Wnt-target genes. Untreated Ldlr{sup ?/?}PON1{sup tg} mice had significantly greater expression of PTHR1 than untreated Ldlr{sup ?/?} mice, whereas sclerostin expression was reduced. In femoral cortical bones, expression levels of transcription factors, FoxO1 and ATF4, were also elevated in the untreated, control Ldlr{sup ?/?}PON1{sup tg} mice, suggesting enhancement of cellular protection against oxidants. These findings suggest that PON1 restores responsiveness to PTH through effects on oxidant stress, PTH receptor expression, and/or Wnt signaling.

Lu, Jinxiu [Department of Physiology, University of California, Los Angeles (United States)] [Department of Physiology, University of California, Los Angeles (United States); Cheng, Henry [Department of Medicine, University of California, Los Angeles (United States)] [Department of Medicine, University of California, Los Angeles (United States); Atti, Elisa [Division of Diagnostic and Surgical Sciences, School of Dentistry, University of California, Los Angeles (United States)] [Division of Diagnostic and Surgical Sciences, School of Dentistry, University of California, Los Angeles (United States); Shih, Diana M. [Department of Medicine, University of California, Los Angeles (United States)] [Department of Medicine, University of California, Los Angeles (United States); Demer, Linda L. [Department of Physiology, University of California, Los Angeles (United States) [Department of Physiology, University of California, Los Angeles (United States); Department of Medicine, University of California, Los Angeles (United States); Department of Bioengineering, University of California, Los Angeles (United States); Tintut, Yin, E-mail: ytintut@mednet.ucla.edu [Department of Medicine, University of California, Los Angeles (United States)] [Department of Medicine, University of California, Los Angeles (United States)

2013-02-01

144

Cinacalcet HCl prevents development of parathyroid gland hyperplasia and reverses established parathyroid gland hyperplasia in a rodent model of CKD  

PubMed Central

Background. Secondary hyperparathyroidism (sHPT) represents an adaptive response to progressively impaired control of calcium, phosphorus and vitamin D in chronic kidney disease (CKD). It is characterized by parathyroid hyperplasia and excessive synthesis and secretion of parathyroid hormone (PTH). Parathyroid hyperplasia in uremic rats can be prevented by calcium-sensing receptor (CaSR) activation with the calcimimetic cinacalcet (Sensipar®/Mimpara®); however, it is unknown, how long the effects of cinacalcet persist after withdrawal of treatment or if cinacalcet is efficacious in uremic rats with established sHPT. Methods. We sought to determine the effect of cinacalcet discontinuation in uremic rats and whether cinacalcet was capable of influencing parathyroid hyperplasia in animals with established sHPT. Results. Discontinuation of cinacalcet resulted in reversal of the beneficial effects on serum PTH and parathyroid hyperplasia. In rats with established sHPT, cinacalcet decreased serum PTH and mediated regression of parathyroid hyperplasia. The cinacalcet-mediated decrease in parathyroid gland size was accompanied by increased expression of the cyclin-dependent kinase inhibitor p21. Prevention of cellular proliferation with cinacalcet occurred despite increased serum phosphorus and decreased serum calcium. Conclusions. The animal data provided suggest established parathyroid hyperplasia can be reversed by modulating CaSR activity with cinacalcet and that continued treatment may be necessary to maintain reductions in PTH. PMID:22036941

Miller, Gerald; Davis, James; Shatzen, Edward; Colloton, Matthew; Martin, David

2012-01-01

145

Stimulation of creatine kinase BB activity by parathyroid hormone and by prostaglandin E2 in cultured bone cells.  

PubMed Central

Bone cells in culture responded to parathyroid hormone (PTH) and prostaglandin E2 (PGE2) by a 2-fold increase in creatine kinase (CK) activity. Combined treatment resulted in a higher response than with PTH alone. Calcitonin (CT) failed to stimulate CK activity, did not affect the response of CK to PTH, but inhibited slightly the increase in CK activity by PGE2. Bone-cell cultures grown in low [Ca2+] (0.125 mM), enriched in PTH-responsive osteoblast-like cells, responded to PTH, but not to PGE2 or CT, by increased CK activity. In both normal and low-[Ca2+] cultures, 8-bromo cyclic AMP did not affect CK activity, nor did it change the response of the cells to PTH, PGE2 or CT. The increase in CK activity was time- and dose-dependent and inhibited both by cycloheximide and by actinomycin D. The isoenzyme of CK stimulated was the CKBB form, the isoenzyme induced by other hormones. This appears to be the first report of the stimulation of CK activity by a polypeptide hormone or a prostaglandin. We suggest that stimulation of CKBB can serve as a marker for the action of a variety of hormones and growth promoters. PMID:3856427

Sömjen, D; Kaye, A M; Binderman, I

1985-01-01

146

Parathyroid carcinoma and oxyphil parathyroid adenoma: an uncommon case of misinterpretation in clinical practice.  

PubMed

A 46 year-old male presented with persistently high level of serum parathyroid hormone (PTH), despite successful resection of an oxyphilic cell parathyroid adenoma of the left lower gland. Renal function and serum calcium were normal, leading to vitamin D deficiency being considered. Tc99m-sestamibi parathyroid scintigraphy showed no capitation, but a cervical ultrasound demonstrated an increase in the lower parathyroids. Surgery confirmed that the right gland was normal but the left corresponded to parathyroid carcinoma. The patient developed severe hypocalcemia, with PTH values being consistent with hypoparathyroidism for a few months. However, a progressive increase in calcium and PTH serum levels indicated recurrence of disease. Tc99m-sestamibi scintigraphy demonstrated hyperfixation in topography of the left inferior parathyroid and the patient was subjected to a third and more extensive surgery, with removal of lymph nodes and adjacent thyroid tissue. Serum calcium and PTH remained elevated, requiring loop diuretics and intravenous bisphosphonates to control hypercalcemia. Cervical radiotherapy was implemented as adjuvant therapy. After two months the patient complained of dyspnea, and a CT scan of the chest demonstrated areas of parenchymal condensation, suggestive of actinic pneumonitis. At the 2-year follow-up no major issues were evident. PMID:23268928

Dytz, Márcio Garrison; Souza, Rodrigo Gomes; Lázaro, Ana Paula Pires; Gonçalves, Manuel Domingos da Cruz; Vidal, Ana Paula Aguiar; dos Santos Teixeira, Patrícia de Fátima; Fleiuss Farias, Maria Lucia

2013-01-01

147

The history of the discovery of vitamin D and its daughter steroid hormone.  

PubMed

It is largely through historical accident in the interval of 1920-1940 that vitamin D(3) became classified as a vitamin rather than as a steroid hormone. The formal definition of a vitamin is that it is a trace dietary constituent required to produce the normal function of a physiological process or processes. The emphasis here is on trace and the fact that the vitamin must be supplied regularly in the diet; this implies that the body is unable to metabolically synthesize the vitamin in question. However, the ultraviolet exposure of 7-dehydrocholesterol present in the skin results in the photochemical production of vitamin D(3). Thus, vitamin D(3) becomes a true vitamin only when the animal or human does not have regular access to sunlight or ultraviolet light. Under normal physiological circumstances, all mammals, including humans, can generate, via ultraviolet exposure of 7-dehydrocholesterol present in the skin, adequate quantities of vitamin D(3) to meet their nutritionally defined requirements. There is a vibrant historical record beginning in 1650 and culminating in 1963 concerned with the determination of the chemical structures of vitamin D(3) and vitamin D(2). A surprising aspect concerning vitamin D(3) is that it is itself biologically inert. There are no known essential biological actions or contributions that rely specifically on the molecule vitamin D(3). While chemists had certainly appreciated the strong structural similarity between the vitamins D and other steroids, this correlation was never widely acknowledged in the biological, clinical, or nutritional sciences until 1965-1970. The biological role of vitamin D(3) is to serve as a substrate for the liver 25-hydroxylase which produces 25-hydroxyvitamin D(3) [25(OH)D(3)]. 25(OH)D(3) in turn serves as the substrate for the kidney proximal tubule 25(OH)D(3)-1?-hydroxylase enzyme which produces the steroid hormone 1?,25(OH)(2)-vitamin D(3) [1?,25(OH)(2)D(3)]. PMID:23183289

Norman, Anthony W

2012-01-01

148

[New Developments in CKD-MBD. Cell Biology of parathyroid in CKD].  

PubMed

Parathyroid monitors the calcium concentration in blood by signals from calcium-sensing receptors, adjusts secretion of parathyroid hormone to keep constant calcium concentration in the body. Although parathyroid parenchymal cells consist of chief cells which secrete PTH, and oxyphil cells which are rich in mitochondria, all hardly perform mitotic proliferation in normal status. However, in CKD, PTH hypersecretion and hyperplasia are started by hyperphosphatemia, hypocalcemia, and activated-vitamin-D deficiency, and the secondary hyperparathyroidism develops. While treatment with cinacalcet hydrochloride salt induced apoptosis into the parathyroid cell, a possibility of promoting the transdifferentiation to oxyphil cells from chief cells was suggested. The specific accumulation to the parathyroid of an oncotropic photosensitizer suggests the possibility of photodynamic diagnosis and treatment of hyperparathyroidism. PMID:25423925

Kakuta, Takatoshi; Sawada, Kaichiro

2014-12-01

149

Impact of race on intraoperative parathyroid hormone kinetics: an analysis of 910 patients undergoing parathyroidectomy for primary hyperparathyroidism.  

PubMed

HYPOTHESIS African American patients exhibit different intraoperative parathyroid hormone (IOPTH) profiles than non-African American patients. DESIGN Retrospective review. SETTING University medical center. PATIENTS Nine hundred ten patients who underwent parathyroidectomy for primary hyperparathyroidism between July 2005 and August 2010. INTERVENTIONS All patients underwent preoperative imaging with ultrasonography and sestamibi; operative exploration; and IOPTH measurement at 2 points preexcision and 5 and 10 minutes postexcision. MAIN OUTCOME MEASURES Preexcision and postexcision IOPTH measurements. RESULTS Of the 910 patients, 734 self-reported their race as white (81%); 91, Latino/other (10%); 56, Asian (6%); and 28, African American (3%). African American patients had significantly higher initial preexcision IOPTH levels compared with white patients (348 vs 202 pg/mL; P = .048) and significantly higher 5-minute postexcision IOPTH levels (151 vs 80 pg/mL; P = .01). The 10-minute postexcision IOPTH levels were similar between the 2 groups (52 vs 50 pg/mL). A similar percentage of white and African American patients had a 50% drop in IOPTH level at 10 minutes postexcision. No differences in IOPTH kinetics were observed in the other racial groups examined. CONCLUSIONS African American patients with primary hyperparathyroidism exhibit significantly higher preincision and 5-minute postexcision IOPTH values when compared with white patients. The 10-minute postexcision IOPTH values did not differ between races. The altered IOPTH kinetics identified in African American patients may reflect the severity of biochemical disease but may also be related to genetically predetermined differences in parathyroid hormone metabolism. PMID:22801754

Cisco, Robin M; Kuo, Jennifer H; Ogawa, Lauren; Scholten, Anouk; Tsinberg, Michael; Duh, Quan-Yang; Clark, Orlo H; Gosnell, Jessica E; Shen, Wen T

2012-11-01

150

Low molecular weight iron dextran increases fibroblast growth factor-23 concentration, together with parathyroid hormone decrease in hemodialyzed patients.  

PubMed

Fibroblast growth factor (FGF)-23 inhibits PTH production. Elevated FGF-23 and parathyroid hormone (PTH) levels are characteristic of hemodialyzed patients. Iron polymaltose was shown to increase FGF-23 concentration. The effect of intravenous low molecular weight iron dextran (LMID) on these hormones and bone metabolism has not been studied in hemodialysis (HD). Twelve HD patients were prospectively followed up for 3 weeks after a single infusion of LMID. Calcium, phosphate, FGF-23, PTH, degradation products of C-terminal telopeptides of type I collagen (CTX) and procollagen I N-terminal propeptide (PINP) were measured prior to, and at week 1 and week 3 after the LMID administration. FGF-23 increased significantly from 453.4 (68.6-3971.5) pg/mL at baseline to 971.8 (779.5-3361.4) pg/mL (P = 0.001) at week 1 and started to decrease toward the initial value at week 3. The changes were accompanied by a significant decline in PTH from 367.6 (21.4-1487.4) pg/mL at baseline to 315.7 (16.4-1339.8) pg/mL (P = 0.018) at week 1 and subsequently began to increase toward the initial values. Phosphate, calcium, CTX and PINP did not change over the study course. LMID causes an increase in FGF-23 concentration together with a decrease in PTH. Our study highlights a pathophysiological element, which may connect suppression of parathyroid glands with intravenous iron supplementation. PMID:22458393

Hryszko, Tomasz; Rydzewska-Rosolowska, Alicja; Brzosko, Szymon; Koc-Zorawska, Ewa; Mysliwiec, Michal

2012-04-01

151

Vitamin D designates a group of calcitriols, fat solu ble hormones of secosteroid nature [1 3]. The calcitriols  

E-print Network

Vitamin D designates a group of calcitriols, fat solu ble hormones of secosteroid nature [1 3]. The calcitriols include vitamins D2, D3, D4, D5, and their derivatives [3]. Vitamin D3 (cholecalciferol, 4]. Vitamin D3 itself is biologi cally inert, and its bioactivation involves double hydroxy lation

Kalueff, Allan V.

152

Pre-diagnostic Circulating Parathyroid Hormone Concentration and Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort  

PubMed Central

Background Parathyroid hormone (PTH) has been proposed to play a promoting role in carcinogenesis. However, no epidemiologic studies have yet directly investigated its role in colorectal cancer (CRC). Methods A case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort was conducted with 1,214 incident, sporadic CRC cases matched to 1,214 controls. Circulating pre-diagnostic PTH and 25-hydroxy vitamin D [25(OH)D] concentrations were measured by enzyme-linked immunosorbent assays. Detailed dietary and lifestyle questionnaire data were collected at baseline. Multivariable conditional logistic regression was used to estimate the incidence rate ratio (RR) with 95% confidence intervals (95%CI) for the association between circulating PTH and CRC risk. Results In multivariate analyses (including adjustment for 25(OH)D concentration) with a priori defined cut-points, high levels of serum PTH (?65ng/L) compared to medium PTH levels of 30–65 ng/L were associated with increased CRC risk (RR=1.41, 95%CI: 1.03-1.93). In analyses by sex, the CRC risk was 1.77 (95%CI: 1.14-2.75) and 1.15 (95%CI: 0.73-1.84) in men and women, respectively (Pheterogeneity=0.01). In sub-group analyses by anatomical sub-site, the risk for colon cancer was RR=1.56, 95%CI:1.03-2.34, and for rectal cancer RR=1.20, 95%CI:0.72-2.01 (Pheterogeneity=0.21). Effect modification by various risk factors was examined. Conclusions The results of this study suggest that high serum PTH levels may be associated with incident, sporadic CRC in Western European populations, and in particular among men. Impact To our knowledge, this is the first study on PTH and CRC. The role of PTH in carcinogenesis needs to be further investigated. PMID:21378267

Fedirko, Veronika; Riboli, Elio; Bueno-de-Mesquita, H. Bas; Rinaldi, Sabina; Pischon, Tobias; Norat, Teresa; Jansen, Eugène H.J.M.; van Duijnhoven, Fränzel J.B.; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Engel, Pierre; Kaaks, Rudolf; Teucher, Birgit; Boeing, Heiner; Buijsse, Brian; Trichopoulou, Antonia; Trichopoulos, Dimitrios; Lagiou, Pagona; Sieri, Sabina; Vineis, Paolo; Panico, Salvatore; Palli, Domenico; Tumino, Rosario; van Gils, Carla H; Peeters, Petra HM; Chirlaque, Maria-Dolores; Gurrea, Aurelio Barricarte; Rodríguez, Laudina; Molina-Montes, Esther; Dorronsoro, Miren; Bonet, Catalina; Palmqvist, Richard; Hallmans, Göran; Key, Timothy J.; Tsilidis, Konstantinos K; Khaw, Kay-Tee; Romieu, Isabelle; Straif, Kurt; Wark, Petra A.; Romaguera, Dora; Jenab, Mazda

2011-01-01

153

Targets for parathyroid hormone in secondary hyperparathyroidism: is a “one-size-fits-all” approach appropriate? A prospective incident cohort study  

PubMed Central

Background Recommendations for secondary hyperparathyroidism (SHPT) consider that a “one-size-fits-all” target enables efficacy of care. In routine clinical practice, SHPT continues to pose diagnosis and treatment challenges. One hypothesis that could explain these difficulties is that dialysis population with SHPT is not homogeneous. Methods EPHEYL is a prospective, multicenter, pharmacoepidemiological study including chronic dialysis patients (?3 months) with newly SHPT diagnosis, i.e. parathyroid hormone (PTH) ?500 ng/L for the first time, or initiation of cinacalcet, or parathyroidectomy. Multiple correspondence analysis and ascendant hierarchical clustering on clinico-biological (symptoms, PTH, plasma phosphorus and alkaline phosphatase) and treatment of SHPT (cinacalcet, vitamin D, calcium, or calcium-free calcic phosphate binder) were performed to identify distinct phenotypes. Results 305 patients (261 with incident PTH???500 ng/L; 44 with cinacalcet initiation) were included. Their mean age was 67?±?15 years, and 60% were men, 92% on hemodialysis and 8% on peritoneal dialysis. Four subgroups of SHPT patients were identified: 1/ “intermediate” phenotype with hyperphosphatemia without hypocalcemia (n?=?113); 2/ younger patients with severe comorbidities, hyperphosphatemia and hypocalcemia, despite SHPT multiple medical treatments, suggesting poor adherence (n?=?73); 3/ elderly patients with few cardiovascular comorbidities, controlled phospho-calcium balance, higher PTH, and few treatments (n?=?75); 4/ patients who initiated cinacalcet (n?=?43). The quality criterion of the model had a cut-off of 14 (>2), suggesting a relevant classification. Conclusion In real life, dialysis patients with newly diagnosed SHPT constitute a very heterogeneous population. A “one-size-fits-all” target approach is probably not appropriate. Therapeutic management needs to be adjusted to the 4 different phenotypes. PMID:25123022

2014-01-01

154

Hip fracture risk in relation to vitamin D supplementation and serum 25-hydroxyvitamin D levels: a systematic review and meta-analysis of randomised controlled trials and observational studies  

Microsoft Academic Search

BACKGROUND: Vitamin D supplementation for fracture prevention is widespread despite conflicting interpretation of relevant randomised controlled trial (RCT) evidence. This study summarises quantitatively the current evidence from RCTs and observational studies regarding vitamin D, parathyroid hormone (PTH) and hip fracture risk. METHODS: We undertook separate meta-analyses of RCTs examining vitamin D supplementation and hip fracture, and observational studies of serum

Jeffrey K C Lai; Robyn M Lucas; Mark S Clements; Andrew W Roddam; Emily Banks

2010-01-01

155

Hormone response element binding proteins: novel regulators of vitamin D and estrogen signaling  

PubMed Central

Insights from vitamin D-resistant New World primates and their human homologues as models of natural and pathological insensitivity to sterol/steroid action have uncovered a family of novel intracellular vitamin D and estrogen regulatory proteins involved in hormone action. The proteins, known as “vitamin D or estrogen response element-binding proteins”, behave as potent cis-acting, transdominant regulators to inhibit steroid receptor binding to DNA response elements and is responsible for vitamin D and estrogen resistances. This set of interactors belongs to the heterogeneous nuclear ribonucleoprotein (hnRNP) family of previously known pre-mRNA-interacting proteins. This review provides new insights into the mechanism by which these novel regulators of signaling and metabolism can act to regulate responses to vitamin D and estrogen. In addition the review also describes other molecules that are known to influence nuclear receptor signaling through interaction with hormone response elements. PMID:21236284

Lisse, Thomas S.; Hewison, Martin; Adams, John S.

2011-01-01

156

Nonfunctional parathyroid carcinoma.  

PubMed Central

Parathyroid carcinoma is a rare entity accounting for 0.5% to 5% of parathyroid neoplasia. Most of these malignancies present as functional hormone-producing masses with elevated serum levels of parathormone and calcium. These tumors may also be nonfunctional. Clinical detection of nonfunctioning parathyroid malignancies preoperatively is primarily based on symptoms of an expanding neck mass. This ominous complaint is typically accompanied with an advanced stage of the disease at initial diagnosis. Because there is a paucity of data in the literature regarding nonfunctioning parathyroid carcinoma, prognosis can not be readily assessed. In both functional and nonfunctional parathyroid carcinoma, early surgery has proven to be the only curative treatment approach whereas both chemotherapy and radiation therapy fail to produce systemic or regional benefit when used alone. Hence, parathyroid cancer should be considered in every patient evaluated for a neck mass regardless of the blood calcium and blood parathormone level. PMID:11491274

Giessler, G. A.; Beech, D. J.

2001-01-01

157

Molecular Structure of the Rat Vitamin D Receptor Ligand Binding Domain Complexed with 2-Carbon-Substituted Vitamin D3 Hormone Analogues and a  

E-print Network

Molecular Structure of the Rat Vitamin D Receptor Ligand Binding Domain Complexed with 2-Carbon-Substituted Vitamin D3 Hormone Analogues and a LXXLL-Containing Coactivator Peptide, Janeen L. Vanhooke,*,| Matthew M of the ligand binding domain (LBD) of the rat vitamin D receptor in ternary complexes with a synthetic LXXLL

Pike, J. Wesley

158

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Neurosteroid hormone vitamin D and its utility in clinical nutrition  

E-print Network

- thesized in skin (as hormone) or ingested with food (as vitamin). Itself biologically inactive, vitamin D functions include the regulation of mineral homeostasis, tissue proliferation, differentiation and apoptosis

Kalueff, Allan V.

159

The expression of the gene coding for parathyroid hormone-related protein (PTHrP) during tooth development in the rat  

Microsoft Academic Search

By means of in situ hybridisation studies, it is shown that parathyroid hormone-related protein (PTHrP) mRNA is strongly expressed in the developing enamel organs of rat teeth. In particular, the cervical loop hybridises strongly with the PTHrP probe and expression is maintained at this site throughout life in the permanently erupting incisor teeth. In mature molar teeth, expression is downregulated

F. Beck; J. Tucci; A. Russell; P. V. Senior; M. W. J. Ferguson

1995-01-01

160

The Effects of Excipients and Particle Engineering on the Biophysical Stability and Aerosol Performance of Parathyroid Hormone (1-34) Prepared as a Dry Powder for Inhalation  

Microsoft Academic Search

Pulmonary delivery of therapeutic peptides and proteins has many advantages including high relative bioavailability, rapid\\u000a systemic absorption and onset of action and a non-invasive mode of administration which improves patient compliance. In this\\u000a study, we investigated the effect of spray-drying (SD) and spray freeze-drying processes on the stability and aerosol performance\\u000a of parathyroid hormone (PTH) (1-34) microparticles. In this study,

Sunday A. Shoyele; Neeraj Sivadas; Sally-Ann Cryan

2011-01-01

161

Parathyroid hormone regulation of bone sialoprotein (BSP) gene transcription is mediated through a pituitary-specific transcription factor-1 (Pit1) motif in the rat BSP gene promoter  

Microsoft Academic Search

Bone sialoprotein (BSP) is a mineralized tissue-specific protein expressed by differentiated osteoblasts that appears to function in the initial mineralization of bone. Parathyroid hormone (PTH), which regulates serum calcium through its actions on bone cells, increases the expression of BSP in the rat osteosarcoma cell line (ROS 17\\/2.8). At 10?8 M PTH (human 1–34 PTH), stimulation of BSP mRNA was

Yorimasa Ogata; Sumi Nakao; Richard H. Kim; Jack J. Li; Shunsuke Furuyama; Hiroshi Sugiya; Jaro Sodek

2000-01-01

162

Parathyroid Hormone-related Peptide (PTHrP)-dependent and -independent Effects of Transforming Growth Factor beta (TGF-beta ) on Endochondral Bone Formation  

Microsoft Academic Search

Previously, we showed that expression of a dominant-negative form of the transforming growth factor b (TGF- b ) type II receptor in skeletal tissue re- sulted in increased hypertrophic differentiation in growth plate and articular chondrocytes, suggesting a role for TGF- b in limiting terminal differentiation in vivo. Parathyroid hormone—related peptide (PTHrP) has also been demonstrated to regulate chondrocyte differentiation

Rosa Serra; Andrew Karaplis; Philip Sohn

1999-01-01

163

Accelerated bone formation and increased osteoblast number contribute to the abnormal tooth germ development in parathyroid hormone-related protein knockout mice  

Microsoft Academic Search

Our previous study showed that tooth germs at late embryonic stage [later than embryonic day 17.5 (E17.5)] and neonatal homozygous parathyroid hormone-related protein (PTHrP)-knockout mice are compressed or penetrated by the surrounding alveolar bone tissue. In vivo and in vitro studies have shown that the development of the tooth germ proper is not disturbed, but insufficient alveolar bone resorption, due

Y. Kitahara; N. Suda; T. Terashima; O. Baba; K. Mekaapiruk; V. E. Hammond; Y. Takano; K. Ohyama

2004-01-01

164

Single-Sperm Typing: Determination of Genetic Distance between the Ggamma -globin and Parathyroid Hormone Loci by Using the Polymerase Chain Reaction and Allele-Specific Oligomers  

Microsoft Academic Search

The frequency of recombination between the Ggamma -globin (HBG2) and parathyroid hormone (PTH) loci on the short arm of human chromosome 11 was estimated by typing >700 single-sperm samples from two males. The sperm-typing technique employed involves the polymerase chain reaction and allele-specific oligonucleotide hybridization. Our maximum likelihood recombination fraction estimate of 0.16 (95% confidence interval, 0.13-0.19) falls well within

Xiangfeng Cui; Honghua Li; Tushar M. Goradia; Kenneth Lange; Haig H. Kazazian; David Galas; Norman Arnheim

1989-01-01

165

Parathyroid hormone decreases HCO3 reabsorption in the rat proximal tubule by stimulating phosphatidylinositol metabolism and inhibiting base exit.  

PubMed Central

The mechanism of inhibition of HCO3 transport by parathyroid hormone (PTH) in the proximal tubule is not clearly defined. Previous studies in vitro have suggested that this effect is mediated via cAMP generation, which acts to inhibit Na/H exchange, resulting in cell acidification. To examine this question in vivo, intracellular pH (pHi) was measured in the superficial proximal tubule of the rat using the pH-sensitive fluoroprobes 4-methylumbelliferone (4MU) and 2',7'-bis(carboxyethyl)-(5, and 6)-carboxyfluorescein (BCECF). PTH was found to alkalinize the cell. This alkalinization suggested inhibition of basolateral base exit, which was confirmed by in situ microperfusion studies: lowering HCO3 in peritubular capillaries acidified the cell, an effect blunted by PTH. Removal of luminal Na promoted basolateral base entry, alkalinizing the cell. This response was also blunted by PTH. Readdition of luminal Na stimulated the luminal Na/H exchanger, causing an alkalinization overshoot that was partially inhibited by PTH. cAMP inhibited luminal H secretion but did not alkalinize the cell. Stimulation of phosphatidylinositol-bis-phosphate turnover by PTH was suggested by the effect to the hormone to increase cell Ca. Blocking the PTH-induced rise in cell Ca blunted the effect of the hormone to alkalinize the cell, as did inhibition of phosphatidylinositol breakdown. Furthermore, stimulation of protein kinase C by a phorbol ester and a diacylglycerol applied basolaterally alkalinized the cell and inhibited luminal H secretion. The findings indicate that both arms of the phosphatidylinositol-bis-phosphate cascade play a role in mediating the effect of PTH on the cell pH. The results are consistent with the view that PTH inhibits base exit in the proximal tubule by activation of the phosphatidylinositol cascade. The resulting alkalinization may contribute, with cAMP, to inhibit apical Na/H exchange and the PTH-induced depression of proximal HCO3 reabsorption. PMID:1314850

Pastoriza-Munoz, E; Harrington, R M; Graber, M L

1992-01-01

166

Vitamins  

MedlinePLUS

... Vitamin D Vitamin E Vitamin K Vitamin B1 ( thiamine ) Vitamin B2 ( riboflavin ) Vitamin B3 ( niacin ) Pantothenic acid ... in the body. Vitamin B12 , like the other B vitamins, is important for metabolism. It also helps form ...

167

Unusual Manifestation of Intravascular Large B-Cell Lymphoma: Severe Hypercalcemia with Parathyroid Hormone-Related Protein  

PubMed Central

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. It usually presents with nonspecific symptoms, such as fever, rather than with overt lymphadenopathy. Reports of hypercalcemia, as the initial presentation of IVLBCL, are limited in the literature, despite it being a well-known complication of various solid cancers. We present a 68-year-old male with severe hypercalcemia and increased levels of serum parathyroid hormone-related protein. He was diagnosed with IVLBCL, involving the bone marrow and spleen, and was successfully treated with rituximab-containing chemotherapy. A few previous case reports have shown hypercalcemia in patients with IVLBCL. Much like our case, previous cases with hypercalcemia had advanced diseases, including bone marrow invasion. Although it was an extremely rare manifestation of IVLBCL, we suggest that IVLBCL should be a part of the differential diagnosis in patients with unexplained hypercalcemia. Therefore, an active work-up might be recommended, including positron emission tomography/ computed tomography scan and bone marrow examination, which may be useful for early diagnosis. PMID:25038766

Ha, Jung Min; Kim, Eun; Lee, Woo Joo; Hwang, Ji-Won; Yune, Sehyo; Ko, Young Hyeh; Choi, Joon Young; Kim, Seok Jin; Kim, Won Seog

2014-01-01

168

Calcium-sensing receptors and parathyroid hormone-related protein in the caudal neurosecretory system of the flounder (Platichthys flesus)  

PubMed Central

The caudal neurosecretory system of the flounder (Platichthys flesus) has been examined by immunocytochemistry and in situ hybridization for the expression of parathyroid hormone-related protein (PTHrP) and calcium-sensing receptors (CaSR). The N-terminus nucleotide and deduced amino acid sequences of flounder PTHrP were determined and used to prepare oligonucleotide probes and homologous antiserum. The Dahlgren cells of the posterior spinal cord and their axons contained PTHrP protein which was also detected around the capillaries of the urophysis. PTHrP gene expression was abundant in the Dahlgren perikarya and axons in the spinal cord, but it was absent from nerve endings in the urophysis. Calcium-sensing receptor protein was present in the Dahlgren perikarya and axons, also with abundant gene expression, but there was neither protein nor mRNA in the urophysis. There were no apparent differences between freshwater- and seawater-adapted fish in either CaSR or PTHrP expression in the caudal neurosecretory system. These observations suggest that Dahlgren cells produce PTHrP which may be released from axons abutting capillaries in the urophysis. However, the sensing of ionic calcium appears to be confined to the perikarya of the Dahlgren cells in the spinal cord neuropil, suggesting that they are responsive to calcium in the central nervous system rather than the general circulation. PMID:12090395

Ingleton, PM; Bendell, LA; Flanagan, JA; Teitsma, C; Balment, RJ

2002-01-01

169

Bone-specific alkaline phosphatase concentrations are less variable than those of parathyroid hormone in stable hemodialysis patients  

PubMed Central

Abnormalities of bone mineral metabolism and vascular calcification are prevalent in patients with kidney failure. Clinical management is based on biochemical targets, in particular parathyroid hormone (PTH) concentrations, but this has many limitations including high biological variation. A possible alternative is bone-specific alkaline phosphatase (ALP); therefore, we evaluated the biological variation of this marker in patients undergoing hemodialysis. Bone ALP was measured in non-fasting serum samples taken twice a week over a 6-week period in 22 stable hemodialysis patients and 12 healthy volunteers. The within-individual coefficients of variance were calculated and used to derive the critical difference required to be certain that an observed change was significant. The coefficient of variance for bone ALP was significantly higher in hemodialysis patients compared to healthy individuals. Seven samples were required to estimate the homeostatic set point of bone ALP, within 10%, in a hemodialysis patient. The concentration of serial bone ALP measurements would need to change by 36% between any two measurements before it can be considered a significant change. Since the biological variation of bone ALP is less than half that reported for PTH, our study provides further support for the use of bone ALP as an alternative marker of bone mineral metabolism in the setting of chronic kidney disease–mineral and bone disorder. PMID:22456600

Sardiwal, Sunita; Gardham, Clare; Coleman, Adrian E; Stevens, Paul E; Delaney, Michael P; Lamb, Edmund J

2012-01-01

170

Development and validation of a novel cell-based assay for potency determination of human parathyroid hormone (PTH).  

PubMed

Parathyroid hormone (PTH) is the primary regulator of serum calcium homeostasis and plays a major role in bone metabolism. Its actions are mediated via the PTH1 receptor (PTH1R) resulting in adenylate cyclase activation and consequently production of cyclic adenosine mono-phosphate (cAMP). The latter stimulates cellular metabolic pathways. This study describes the development, validation and applications of a novel cell-based potency assay for PTH using HEK293 cells over-expressing PTH1R. PTH concentration-dependent cAMP formation in these cells was quantitatively analyzed employing time-resolved fluorescence technology (TR-FRET). The optimized assay was precise, reproducible and exhibited a high sensitivity to PTH with a limit of quantification in the low picogram range. The potencies of differently manufactured PTH1-34 peptides, as well as a full-length variant (PTH1-84), were all accurately measured. Since PTH activity is inhibited by neutralizing antibodies against PTH, the assay was adapted to detect and measure neutralizing antibodies in human serum. Thus, applications of this novel cell-based PTH potency assay were extended to immunogenicity testing of PTH preparations in non-clinical and clinical settings. PMID:24996007

Hohenstein, Axel; Hebell, Meike; Zikry, Heidi; El Ghazaly, Maria; Mueller, Frank; Rohde, Jan

2014-09-01

171

Electrogenic Na?/HCO?? co-transporter-1 is essential for the parathyroid hormone-stimulated intestinal HCO?? secretion.  

PubMed

Parathyroid hormone (PTH) was recently demonstrated to enhance the HCO(3)(-) secretion through the apical anion channel, cystic fibrosis transmembrane conductance regulator (CFTR), but how the HCO(3)(-) entered the epithelial cells was not well understood, in part, due to the lack of specific inhibitors of the basolateral HCO(3)(-) transporters. Moreover, the function of the PTH-stimulated HCO(3)(-) secretion has never been investigated in vivo. Here, we designed three specific pairs of small interfering RNA sequences to simultaneously knockdown three variants of the electrogenic Na(+)/HCO(3)(-) co-transporter (NBCe)-1 in the intestinal epithelium-like Caco-2 monolayer. The results showed that NBCe1 mRNA levels were markedly reduced, and the PTH-induced transepithelial current and voltage changes were diminished after triple knockdown as determined by quantitative real-time PCR and Ussing chamber technique, respectively. An in vivo ligated intestinal loop study further showed that there was an increased fluid secretion, presumably driven by HCO(3)(-) transport, in the ileum, but not in jejunum or colon, of rats administered intravenously with 2 ?g/kg body weight of rat PTH 1-34. Therefore, the present results suggested that PTH stimulated intestinal HCO(3)(-) secretion, particularly in the ileum, by inducing the basolateral HCO(3)(-) uptake via NBCe1. PMID:21621518

Charoenphandhu, Narattaphol; Laohapitakworn, Suparerk; Kraidith, Kamonshanok; Nakkrasae, La-Iad; Jongwattanapisan, Prapaporn; Tharabenjasin, Phuntila; Krishnamra, Nateetip

2011-06-17

172

Immunohistochemical analyses of parathyroid hormone-dependent downregulation of renal type II Na-Pi cotransporters by cryobiopsy.  

PubMed

The "in vivo cryotechnique" (IVCT) is a new method of morphological analysis which has the advantage of freezing tissues in living animals without stopping their blood circulation. The purpose of this study was to investigate the effect of parathyroid hormone (PTH) on renal type II Na-Pi transporters (NaPi-IIa and NaPi-IIc) and "cryobiopsy" (CB) using special cryoforceps as a simple method of the IVCT. The kidney tissues were biopsied at various time points after PTH administration by CB using liquid nitrogen as the cryogen. By hematoxylin-eosin (HE) staining the kidney tissues, well-frozen areas without visible ice crystals were obtained in the tissue surface areas, and the brush border membrane (BBM) of proximal tubules was well preserved at a light microscopic level. Immunohistochemical evaluation showed that PTH downregulated NaPi-IIa and NaPi-IIc at the BBM, being controlled by a different mechanism. In this method, the PTH-induced internalization of NaPi-IIc from microvilli to subapical compartments was not observed in the tissue preparations. NaPi-IIc protein appears to be degraded in microvilli of the proximal tubular cells after the injection of PTH. We suggest that CB using liquid nitrogen is useful to investigate renal type II Na-Pi transporters at the light microscopic level. PMID:20299753

Matsumoto, Natsuki; Hemmi, Akihiro; Yamato, Hideyuki; Ohnishi, Ritsuko; Segawa, Hiroko; Ohno, Shinichi; Miyamoto, Ken-ichi

2010-02-01

173

Serum parathyroid hormone (PTH) in pregnant women determined by an immunoradiometric assay for intact PTH  

SciTech Connect

Most studies of circulating PTH levels using traditional RIAs have supported the concept of physiological hyperparathyroidism of pregnancy, with pregnant women having serum immunoreactive PTH levels significantly higher than those in nonpregnant subjects. However, such RIAs are insensitive and often detect inactive PTH fragments, so that the correlation between PTH immunoreactivity and bioactivity is poor. Employing a new intact PTH immunoradiometric assay (Allegro-Nichols), we reassessed the effects of pregnancy on parathyroid function. The mean serum PTH level in 81 pregnant women was 14.4 +/- 6.3 (+/- SD) compared to 24.8 +/- 9.0 ng/L in 11 normally cycling nonpregnant women (P less than 0.001). The mean serum total and ionized calcium levels in the 2 groups were similar. In 5 of the pregnant women, serum bioactive PTH, determined by cytochemical bioassay, was slightly lower (7.7 +/- 3.4 ng/L) than in normal individuals (11.1 +/- 1.9 ng/L). Our findings suggest, in contrast with the results of most previous studies, that serum intact PTH may decline during pregnancy.

Davis, O.K.; Hawkins, D.S.; Rubin, L.P.; Posillico, J.T.; Brown, E.M.; Schiff, I.

1988-10-01

174

Experienced radio-guided surgery teams can successfully perform minimally invasive radio-guided parathyroidectomy without intraoperative parathyroid hormone assays.  

PubMed

Minimally invasive parathyroidectomy is an accepted treatment option for primary hyperparathyroidism. The need for intraoperative parathyroid hormone assays (iPTH) to confirm adenoma removal remains controversial. We studied minimally invasive radio-guided parathyroidectomy (MIRP) performed using preoperative sestamibi localization studies, intraoperative gamma detection probe, and the selective use of frozen section pathology without the use of iPTH. This is a single institution review of patients with primary hyperparathyroidism treated with MIRP by surgeons experienced in radio-guided surgery between October 1, 1998 and July 15, 2005. Information was obtained by reviewing computer medical records as well as contacting primary care physicians. Factors evaluated included laboratory values, pathology results, and evidence of recurrence. One hundred forty patients were included with a median preoperative calcium level of 11.3 mg/dL (range, 9.6-17) and a PTH level of 147 pg/mL (range, 19-5042). The median postoperative calcium level was 9.3 mg/dL. All patients were initially eucalcemic postoperatively except for one who had normal parathyroid levels. However, five (4%) patients required re-exploration for various reasons. Of the failures, one was secondary to the development of secondary hyperparathyroidism, and therefore would not have benefited from iPTH, one had thyroid tissue removed at the first operation, and three developed evidence of a second adenoma. One of these three patients had a drop in PTH level from 1558 pg/mL preoperatively to 64 pg/mL on postoperative Day 1, indicating that iPTH would not have prevented this failure. Thus, only three (2.1%) patients could have potentially benefited from the use of iPTH. MIRP was successful in 96 per cent of patients using a combination of preoperative sestamibi scans, intraoperative localization with a gamma probe, and the selective use of frozen pathology. This correlates with reported success rates of 95 per cent to 100 per cent using iPTH. We conclude that minimally invasive parathyroidectomy can be successfully performed without using iPTH assays. PMID:16986387

Caudle, Abigail S; Brier, Sarah E; Calvo, Benjamin F; Kim, Hong Jin; Meyers, Michael O; Ollila, David W

2006-09-01

175

The relationship between insulin, insulin resistance, parathyroid hormone, cortisol, testosterone, and thyroid function tests in the presence of nephrolithiasis: a comprehensive analysis  

PubMed Central

Introduction Previous studies have shown that hormonal factors such as levels of insulin, cortisol, testosterone, and insulin resistance are related with increased nephrolithiasis (NL). However, no previous study has evaluated the relationship between insulin, insulin resistance, thyroid hormones, cortisol, intact parathyroid hormone and testosterone levels with the presence of NL in a comprehensive manner. Materials and methods All patients underwent the following procedures: history taking, physical examination, biochemical analysis [including measurement of levels of insulin, thyroid hormones, cortisol, and total testosterone (for male patients only)], urine analysis, 24–hour urine collection to measure urinary protein, sodium excretion, and creatinine clearance. Insulin resistance was evaluated by the homeostasis model assessment index (HOMA–INDEX). The presence of NL was determined by ultrasonography. Results The study was composed of 136 patients. In total, 30 patients had NL. Patients with NL were more likely to be older, male, obese, and smokers. Uric acid and HOMA–INDEX were also higher in patients with NL. In the whole group, only insulin (Odds ratio:1.128, CI:1.029–1.236, P:0.01) but not other hormones, and HOMA–INDEX were related with the presence of NL. In males, none of the hormones including total testosterone were associated with NL. Conclusions Only levels of insulin, but not other hormones were associated with the presence of NL in a group of patients with suspicion of NL. More studies are needed to highlight the mechanisms regarding NL and hormone levels. PMID:24982784

Karaca, Halit

2014-01-01

176

Paraneoplastic hormones: parathyroid hormone-related protein (PTHrP) and erythropoietin (EPO) are related to vascular endothelial growth factor (VEGF) expression in clear cell renal cell carcinoma.  

PubMed

To investigate the correlation between parathyroid hormone-related protein (PTHrP), erythropoietin (EPO), and vascular endothelial growth factor (VEGF) expression in clear cell renal cell carcinoma (ccRCC). Immunohistochemical studies on PTHrP, EPO and VEGF were performed in 249 patients with ccRCC. Serum calcium level and haematocrit were analyzed. The expression of the factors and clinicopathological parameters were studied statistically for possible correlations. The incidence for hypercalcaemia and polycythaemia were 15.3% and 2.0% respectively. Expression of PTHrP, EPO, and VEGF were respectively related to advanced stage (P < 0.0001 respectively). PTHrP was not related to tumour grade. Expressions of EPO and VEGF were correlated to tumour grade significantly. All factors were expressed higher in hypercalcaemic patients. PTHrP, EPO, and VEGF were positively correlated with each other in non-hypercalcaemic patients yet not in hypercalcaemic ones. PTHrP and EPO are related to VEGF expression and to the progression of ccRCC. This finding offers us new insight on the behaviour of ccRCC and offers possible targets in RCC treatment. PMID:23780896

Feng, Chen-chen; Ding, Guan-xiong; Song, Ning-hong; Li, Xuan; Wu, Zhong; Jiang, Hao-wen; Ding, Qiang

2013-12-01

177

Single-dose cholecalciferol suppresses the winter increase in parathyroid hormone concentrations in healthy older men and women: a randomized triaI?3  

Microsoft Academic Search

A randomized double-blind controlled trial of a single oral dose of 2.5 mg(100 000 IU) cholecalciferol (vitamin D3) was conducted in the winter in 189 healthy free-living men and women aged 63-76 y. The mean baseline serum concentra- tion for 25-hydroxyvitamin D was 34.5 nmolfL and for parathy- roid hormone 3.18 pmolIL. After 5 wk, mean serum 25-hydroxy- vitamin D

Kay-Tee Khaw; Robert Scragg; Sean Murphy

178

Effect of aluminium hydroxide on serum ionised calcium, immunoreactive parathyroid hormone, and aluminium in chronic renal failure.  

PubMed

According to the Bricker-Slatopolsky theory, secretion of parathyroid hormone (PTH) is switched on in chronic renal failure by hypocalcaemia due to phosphate retention. In an attempt to reverse this process 20 patients in preterminal renal failure (plasma creatinine 569 +/- 195 mumol/l) were given aluminium hydroxide, 3.8 g daily. They were studied for four weeks and all measurements were made at the start and weekly, except measurements of serum aluminium concentration, which were made at the start and at the end of the fourth week. Mean serum phosphate fell from 1.89 to 1.47 mmol/l (5.9 to 4.6 mg/100), mean serum calcium rose from 2.07 to 2.24 mmol/l (8.3 to 9.0 mg/100 ml), and serum ionised calcium rose from 1.07 to 1.20 mmol/l (4.3 to 4.8 mg/100 ml), but serum immunoreactive PTH did not fall. Thirteen patients had initial serum immunoreactive PTH concentrations at or near to normal and 11 were taking beta-blockers but even in those with neither explanation, PTH concentrations did not fall. Serum aluminium concentrations rose from 0.4 to 1.02 mumol/l (10.9 to 27.4 microgram/l). Aluminium hydroxide corrects serum phosphate, total calcium, and ionised calcium at the price of a rise in serum aluminium concentration; in this study it did not affect serum immunoreactive PTH. The Bricker-Slatopolsky theory still needs verification in studies of patients with chronic renal failure. PMID:6802224

Biswas, C K; Arze, R S; Ramos, J M; Ward, M K; Dewar, J H; Kerr, D N; Kenward, D H

1982-03-13

179

Bone-invasive oral squamous cell carcinoma in cats: pathology and expression of parathyroid hormone-related protein.  

PubMed

Feline oral squamous cell carcinoma (OSCC) is the most common oral tumor in cats. There is no effective treatment, and the average duration of survival after diagnosis is only 2 months. Feline OSCC is frequently associated with osteolysis; however, the mechanisms responsible are unknown. The objective of this study was to characterize the epidemiology and pathology of bone-invasive OSCC in cats and to determine the expression of select bone resorption agonists. In sum, 451 cases of feline OSCC were evaluated. There was no sex or breed predisposition, although there were more intact cats in the OSCC group compared to the control group. Gingiva was the most common site, followed by the sublingual region and tongue. Cats with lingual OSCC were younger (mean, 11.9 years) compared to cats with gingival OSCC (mean, 13.6 years). In addition to osteolysis, there was periosteal new bone formation, osseous metaplasia of tumor stroma, and direct apposition of OSCC to fragments of bone, suggestive of bone-binding behavior. Eighty-two cases were selected for immunohistochemical detection of parathyroid hormone-related protein (PTHrP). Specimens with osteolysis had increased PTHrP expression and nuclear localization, compared to OSCC without osteolysis. Thirty-eight biopsies of OSCC with osteolysis were evaluated for tumor necrosis factor ? expression, and only 4 biopsies had such expression in a small proportion of tumor cells. Increased tumor expression of PTHrP and increased localization of PTHrP to the nucleus were associated with osteolysis and may play an important role in bone resorption and tumor invasion in cats with OSCC. PMID:20940448

Martin, C K; Tannehill-Gregg, S H; Wolfe, T D; Rosol, T J

2011-01-01

180

Roles of parathyroid hormone (PTH) receptor and reactive oxygen species in hyperlipidemia-induced PTH resistance in preosteoblasts.  

PubMed

Bioactive lipids initiate inflammatory reactions leading to pathogenesis of atherosclerosis. Evidence shows that they also contribute to bone loss by inhibiting parathyroid hormone receptor (PTH1R) expression and differentiation of osteoblasts. We previously demonstrated that bone anabolic effects of PTH(1-34) are blunted in hyperlipidemic mice and that these PTH effects are restored by antioxidants. However, it is not clear which osteoblastic cell developmental stage is targeted by bioactive lipids. To investigate the effects of hyperlipidemia at the cellular level, hyperlipidemic Ldlr(-/-) mice were bred with Col3.6GFPtpz mice, in which preosteoblasts/osteoblasts carry a topaz fluorescent label, and with Col2.3GFPcyan mice, in which more mature osteoblasts/osteocytes carry a cyan fluorescent label. Histological analyses of trabecular bone surfaces in femoral as well as calvarial bones showed that intermittent PTH(1-34) increased fluorescence intensity in WT-Tpz mice, but not in Tpz-Ldlr(-/-) mice. In contrast, PTH(1-34) did not alter fluorescence intensity in femoral cortical envelopes of either WT-Cyan or Ldlr(-/-)-Cyan mice. To test the mechanism of PTH1R downregulation, preosteoblastic MC3T3-E1 cells were treated with bioactive lipids and the antioxidant Trolox. Results showed that inhibitory effects of PTH1R levels by bioactive lipids were rescued by pretreatment with Trolox. The inhibitory effects on expression of PTH1R as well as on PTH-induced osteoblastic genes were mimicked by xanthine/xanthine oxidase, a known generator of reactive oxygen species. These findings suggest an important role of the preosteoblastic development stage as the target and downregulation of PTH receptor expression mediated by intracellular oxidant stress as a mechanism in hyperlipidemia-induced PTH resistance. PMID:24038594

Li, Xin; Garcia, Jamie; Lu, Jinxiu; Iriana, Sidney; Kalajzic, Ivo; Rowe, David; Demer, Linda L; Tintut, Yin

2014-01-01

181

Parathyroid hormone administration improves bone marrow microenvironment and partially rescues haematopoietic defects in Bmi1-null mice.  

PubMed

The epigenetic regulator Bmi1 is key in haematopoietic stem cells, and its inactivation leads to defects in haematopoiesis. Parathyroid hormone (PTH), an important modulator of bone homeostasis, also regulates haematopoiesis, so we asked whether PTH administration improves bone marrow microenvironment and rescues the haematopoietic defects in Bmi1-null mice. The mice were treated with PTH1-34 (containing the first 34 residues of mature PTH), an anabolic drug currently used for treating osteoporosis, and compared with the vehicle-treated Bmi1-/- and wild-type littermates in terms of skeletal and haematopoietic phenotypes. We found that the administration significantly increased all parameters related to osteoblastic bone formation and significantly reduced the adipocyte number and PPAR? expression. The bone marrow cellularity, numbers of haematopoietic progenitors and stem cells in the femur, and numbers of lymphocytes and other white blood cells in the peripheral blood all increased significantly when compared to vehicle-treated Bmi1-/- mice. Moreover, the number of Jagged1-positive cells and percentage of Notch intracellular domain-positive bone marrow cells and protein expression levels of Jagged1 and NICD in bone tissue were also increased in Bmi1-/- mice upon PTH1-34 administration,whereas the up-regulation of PTH on both Notch1 and Jagged1 gene expression was blocked by the Notch inhibitor DAPT administration. These results thus indicate that PTH administration activates the notch pathway and partially rescues haematopoietic defects in Bmi1-null mice, further suggesting that haematopoietic defects in the animals are not only a result of reduced self-renewal of haematopoietic stem cells but also due to impaired bone marrow microenvironment. PMID:24705625

Lu, Ruinan; Wang, Qian; Han, Yongli; Li, Jianyong; Yang, Xiang-Jiao; Miao, Dengshun

2014-01-01

182

Parathyroid hormone monotherapy and cotherapy with antiresorptive agents restore vertebral bone mass and strength in aged ovariectomized rats.  

PubMed

Previous studies have shown that parathyroid hormone (PTH) monotherapy and cotherapy with estrogen or risedronate augment vertebral bone mass and bone strength in young, ovariectomized (OVX) rats. The current study was designed to determine whether PTH has similar bone anabolic effects in aged OVX rats at a much later stage of estrogen depletion. Female Sprague Dawley rats were subjected to sham surgery or bilateral ovariectomy at three months of age and maintained untreated for one year after surgery to allow for the development of vertebral osteopenia in OVX rats. Groups of baseline control and OVX rats were sacrificed at the end of this pretreatment period. The remaining OVX rats were then treated for ten weeks with vehicle, antiresorptive agents alone (estrogen, risedronate, or calcitonin), or PTH alone. Other groups of OVX rats were treated concurrently with PTH and each of the antiresorptive agents. The first and fourth lumbar vertebral bodies were processed undecalcified for quantitative bone histomorphometry and biomechanical testing, respectively. As expected, bone mass and compressive strength were decreased in the lumbar vertebral body of baseline OVX rats compared to baseline control rats. This bone loss was associated with decreases in trabecular number and width and an increase in trabecular separation. Treatment with estrogen, risedronate, or calcitonin alone failed to reverse the changes in bone mass, structure, and strength induced by ovariectomy. In contrast, treatment of OVX rats with PTH alone restored vertebral cancellous bone volume and ash density to the level of vehicle-treated control rats and increased vertebral maximum load, stress, and normalized load to well above this level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7669439

Li, M; Mosekilde, L; Søgaard, C H; Thomsen, J S; Wronski, T J

1995-06-01

183

Skeletal unloading causes resistance of osteoprogenitor cells to parathyroid hormone and to insulin-like growth factor-I  

NASA Technical Reports Server (NTRS)

Skeletal unloading decreases bone formation and osteoblast number in vivo and decreases the number and proliferation of bone marrow osteoprogenitor (BMOp) cells in vitro. We tested the ability of parathyroid hormone (PTH) to stimulate BMOp cells in vivo by treating Sprague Dawley rats (n = 32) with intermittent PTH(1-34) (1 h/day at 8 microg/100 g of body weight), or with vehicle via osmotic minipumps during 7 days of normal weight bearing or hind limb unloading. Marrow cells were flushed from the femur and cultured at the same initial density for up to 21 days. PTH treatment of normally loaded rats caused a 2.5-fold increase in the number of BMOp cells, with similar increases in alkaline phosphatase (ALP) activity and mineralization, compared with cultures from vehicle-treated rats. PTH treatment of hind limb unloaded rats failed to stimulate BMOp cell number, ALP activity, or mineralization. Hind limb unloading had no significant effect on PTH receptor mRNA or protein levels in the tibia. Direct in vitro PTH challenge of BMOp cells isolated from normally loaded bone failed to stimulate their proliferation and inhibited their differentiation, suggesting that the in vivo anabolic effect of intermittent PTH on BMOp cells was mediated indirectly by a PTH-induced factor. We hypothesize that this factor is insulin-like growth factor-I (IGF-I), which stimulated the in vitro proliferation and differentiation of BMOp cells isolated from normally loaded bone, but not from unloaded bone. These results suggest that IGF-I mediates the ability of PTH to stimulate BMOp cell proliferation in normally loaded bone, and that BMOp cells in unloaded bone are resistant to the anabolic effect of intermittent PTH therapy due to their resistance to IGF-I.

Kostenuik, P. J.; Harris, J.; Halloran, B. P.; Turner, R. T.; Morey-Holton, E. R.; Bikle, D. D.

1999-01-01

184

Validation of a simple RP-HPLC method developed for the quantification of meta-cresol in parathyroid hormones formulation  

PubMed Central

Aim: To develop and validate a rapid and sensitive reverse phase high performance liquid chromatography (RP-HPLC) method with UV detection for quantification of meta-cresol (m-cresol) in pharmaceutical preparation of parathyroid hormone (1–34) (PTH). Materials and Methods: Chromatography was performed on a Jupiter RP C-18 (4.6 mm ID × 250 mm L, porosity 300 Å, particle size 5 ?m) with a guard column (reversed-phase C18 column of 4.6 mm ID × 12.5 mm L, porosity 300 Å, particle size 5 ?m) using a mobile phase containing 0.1% TFA in 60% methanol with isocratic program at 1.0 mL/min flow rate. Detection was carried out at 217 nm. The method was validated as per ICH guidelines for linearity (correlation coefficient = 0.99), range, accuracy, precision, and robustness (n = 9 during accuracy parameter whereas n =15 during linearity and range parameter and n = 6 during repeatability). Robustness was confirmed by considering two factors; age effect of the mobile phase and test sample and with different columns during method development. Results: The method was linear over the concentration range of 75–120 ?g/mL. The precision of the method in terms of relative standard deviation was evaluated from intra- and inter-day replicate injections of system suitability standards of m-cresol using different equipment and different columns. Components of within- and between-batch variances were found to be below 2% (n = 30) and 3%, respectively, which constituted an acceptable level of variation. Retention time was found to be about 5.2 min and 10.9 min for m-cresol and PTH, respectively. Conclusion: The developed method thus has the potential of being useful for routine quality control of m-cresol. PMID:23781457

Rane, Shaligram S.; Ajameri, Alkesh; Mody, Rustom; Padmaja, P.

2011-01-01

185

[Preparation and identification of recombinant adenoviruses carrying short hairpin RNA targeting parathyroid hormone related protein of goat].  

PubMed

Parathyroid hormone related protein (PTHrP) has important biological functions in calcium metabolism. The aim of this study was to silence the expression of PTHrP by RNA interference and recombinant adenovirus, and to provide a material to investigate the relative functions of PTHrP in goat mammary gland epithelial cell. The Block-iT shRNA interference system was used in this experiment. We designed and synthesized two pairs of complementary single-strand DNA oligonucleotides (shRNA-322/357) targeting two different sites of PTHrP mRNA. Then the oligonucleotides were inserted into shuttle vector pENTR/CMV-GFP/U6. After detection of the interference efficiency by Western blotting, we chose pENTR/CMV-GFP/U6-322 and adenovirus backbone vector pAD/PL-DEST to produce recombinant vector pAD/PL-DEST/CMV-GFP/U6-322. The first generation recombinant adenovirus particles (AD-PTHrP-322) were produced and further amplified by transfecting HEK-293 cells. The titer of the recombinant adenovirus reached 2.0 x 1(9) PFU/mL determined by TCID50 assays. The result of real-time quantitative PCR indicated that mRNA expression levels of gene were reduced 29.2%, 68.1% and 82.6% (P < 0.05), respectively, when goat mammary gland epithelial cells were infected with AD-PTHrP-322 after 24, 48 and 72 h, in which PTHrP. Western blotting also showed that the expression of PTHrP was reduced by infecting the cells with AD-PTHrP-322. AD-PTHrP-322 has been proved with significant interference effect on expression of PTHrP. PMID:22393710

Xing, Ruifang; Zheng, Huiling; Liu, Xuemei; Yan, Linhui; An, Junhui; Yang, Zhenyu; Zhu, Zhenzhen

2011-11-01

186

Recombinant Human Parathyroid Hormone Related Protein 1-34 and 1-84 and Their Roles in Osteoporosis Treatment  

PubMed Central

Osteoporosis is a common disorder characterized by compromised bone strength that predisposes patients to increased fracture risk. Parathyroid hormone related protein (PTHrP) is one of the candidates for clinical osteoporosis treatment. In this study, GST Gene Fusion System was used to express recombinant human PTHrP (hPTHrP) 1-34 and 1-84. To determine whether the recombinant hPTHrP1-34 and 1-84 can enhance renal calcium reabsorption and promote bone formation, we examined effects of recombinant hPTHrP1-34 and 1-84 on osteogenic lineage commitment in a primary bone marrow cell culture system and on osteoporosis treatment. Results revealed that both of recombinant hPTHrP1-34 and 1-84 increased colony formation and osteogenic cell differentiation and mineralization in vitro; however, the effect of recombinant hPTHrP1-84 is a little stronger than that of hPTHrP1-34. Next, ovariectomy was used to construct osteoporosis animal model (OVX) to test activities of these two recombinants in vivo. HPTHrP1-84 administration elevated serum calcium by up-regulating the expression of renal calcium transporters, which resulted in stimulation of osteoblastic bone formation. These factors contributed to augmented bone mass in hPTHrP1-84 treated OVX mice but did not affect bone resorption. There was no obvious bone mass alteration in hPTHrP1-34 treated OVX mice, which may be, at least partly, associated with shorter half-life of hPTHrP1-34 compared to hPTHrP1-84 in vivo. This study implies that recombinant hPTHrP1-84 is more effective than hPTHrP1-34 to enhance renal calcium reabsorption and to stimulate bone formation in vivo. PMID:24516619

Wang, Hua; Liu, Jingning; Yin, Ying; Wu, Jun; Wang, Zilu; Miao, Dengshun; Sun, Wen

2014-01-01

187

Parathyroid Hormone Administration Improves Bone Marrow Microenvironment and Partially Rescues Haematopoietic Defects in Bmi1-Null Mice  

PubMed Central

The epigenetic regulator Bmi1 is key in haematopoietic stem cells, and its inactivation leads to defects in haematopoiesis. Parathyroid hormone (PTH), an important modulator of bone homeostasis, also regulates haematopoiesis, so we asked whether PTH administration improves bone marrow microenvironment and rescues the haematopoietic defects in Bmi1-null mice. The mice were treated with PTH1-34 (containing the first 34 residues of mature PTH), an anabolic drug currently used for treating osteoporosis, and compared with the vehicle-treated Bmi1-/- and wild-type littermates in terms of skeletal and haematopoietic phenotypes. We found that the administration significantly increased all parameters related to osteoblastic bone formation and significantly reduced the adipocyte number and PPAR? expression. The bone marrow cellularity, numbers of haematopoietic progenitors and stem cells in the femur, and numbers of lymphocytes and other white blood cells in the peripheral blood all increased significantly when compared to vehicle-treated Bmi1-/- mice. Moreover, the number of Jagged1-positive cells and percentage of Notch intracellular domain-positive bone marrow cells and protein expression levels of Jagged1 and NICD in bone tissue were also increased in Bmi1-/- mice upon PTH1-34 administration,whereas the up-regulation of PTH on both Notch1 and Jagged1 gene expression was blocked by the Notch inhibitor DAPT administration. These results thus indicate that PTH administration activates the notch pathway and partially rescues haematopoietic defects in Bmi1-null mice, further suggesting that haematopoietic defects in the animals are not only a result of reduced self-renewal of haematopoietic stem cells but also due to impaired bone marrow microenvironment. PMID:24705625

Lu, Ruinan; Wang, Qian; Han, Yongli; Li, Jianyong; Yang, Xiang-Jiao; Miao, Dengshun

2014-01-01

188

ORIGINAL ARTICLE JBMR The Calcium-Sensing Receptor Mediates Bone Turnover Induced by Dietary Calcium and Parathyroid Hormone in  

E-print Network

We have investigated, in neonates, whether the calcium-sensing receptor (CaR) mediates the effects of dietary calcium on bone turnover and/or modulates parathyroid hormone (PTH)–induced bone turnover. Wild-type (WT) pups and pups with targeted deletion of the Pth (Pth –/ – ) gene or of both Pth and CaR (Pth –/ – CaR –/ – ) genes were nursed by dams on a normal or high-calcium diet. Pups nursed by dams on a normal diet received daily injections of vehicle or of PTH(1–34) (80 mg/kg) for 2 weeks starting from 1 week of age. In pups receiving vehicle and fed by dams on a normal diet, trabecular bone volume, osteoblast number, type 1 collagen–positive area, and mineral apposition rate, as well as the expression of bone-formation-related genes, all were reduced significantly in Pth –/ – pups compared with WT pups and were decreased even more dramatically in Pth –/ – CaR –/ – pups. These parameters were increased in WT and Pth –/ – pups but not in Pth –/ – CaR –/ – pups fed by dams on a high-calcium diet compared with pups fed by dams on a normal diet. These parameters also were increased in WT, Pth –/ – , and Pth –/ – CaR –/ – pups following exogenous PTH treatment; however, the percentage increase was less in Pth –/ – CaR –/ – pups than in WT and Pth –/ – pups. In vehicle-treated pups fed by dams on either the normal or high-calcium diet and in PTHtreated pups fed by dams on a normal diet, the number and surfaces of osteoclasts and the ratio of RANKL/OPG were reduced significantly in Pth –/ – pups and less significantly in Pth –/ – CaR –/ – pups compared with WT pups. These parameters were further reduced

Lei Shu; Ji Ji; Qi Zhu; Guofan Cao; Andrew Karaplis; Martin R Pollak; Edward Brown; David Goltzman; Dengshun Miao

189

Insulin-like growth factor I is required for the anabolic actions of parathyroid hormone on mouse bone  

NASA Technical Reports Server (NTRS)

Parathyroid hormone (PTH) is a potent anabolic agent for bone, but the mechanism(s) by which it works remains imperfectly understood. Previous studies have indicated that PTH stimulates insulin-like growth factor (IGF) I production, but it remains uncertain whether IGF-I mediates some or all of the skeletal actions of PTH. To address this question, we examined the skeletal response to PTH in IGF-I-deficient (knockout [k/o]) mice. These mice and their normal littermates (NLMs) were given daily injections of PTH (80 microg/kg) or vehicle for 2 weeks after which their tibias were examined for fat-free weight (FFW), bone mineral content, bone structure, and bone formation rate (BFR), and their femurs were assessed for mRNA levels of osteoblast differentiation markers. In wild-type mice, PTH increased FFW, periosteal BFR, and cortical thickness (C.Th) of the proximal tibia while reducing trabecular bone volume (BV); these responses were not seen in the k/o mice. The k/o mice had normal mRNA levels of the PTH receptor and increased mRNA levels of the IGF-I receptor but markedly reduced basal mRNA levels of the osteoblast markers. Surprisingly, these mRNAs in the k/o bones increased several-fold more in response to PTH than the mRNAs in the bones from their wild-type littermates. These results indicate that IGF-I is required for the anabolic actions of PTH on bone formation, but the defect lies distal to the initial response of the osteoblast to PTH.

Bikle, Daniel D.; Sakata, Takeshi; Leary, Colin; Elalieh, Hashem; Ginzinger, David; Rosen, Clifford J.; Beamer, Wesley; Majumdar, Sharmila; Halloran, Bernard P.

2002-01-01

190

Nmp4/CIZ suppresses the parathyroid hormone anabolic window by restricting mesenchymal stem cell and osteoprogenitor frequency.  

PubMed

Parathyroid hormone (PTH) anabolic osteoporosis therapy is intrinsically limited by unknown mechanisms. We previously showed that disabling the transcription factor Nmp4/CIZ in mice expanded this anabolic window while modestly elevating bone resorption. This enhanced bone formation requires a lag period to materialize. Wild-type (WT) and Nmp4-knockout (KO) mice exhibited equivalent PTH-induced increases in bone at 2 weeks of treatment, but by 7 weeks, the null mice showed more new bone. At 3-week treatment, serum osteocalcin, a bone formation marker, peaked in WT mice, but continued to increase in null mice. To determine if 3 weeks is the time when the addition of new bone diverges and to investigate its cellular basis, we treated 10-week-old null and WT animals with human PTH (1-34) (30??g/kg/day) or vehicle before analyzing femoral trabecular architecture and bone marrow (BM) and peripheral blood phenotypic cell profiles. PTH-treated Nmp4-KO mice gained over 2-fold more femoral trabecular bone than WT by 3 weeks. There was no difference between genotypes in BM cellularity or profiles of several blood elements. However, the KO mice exhibited a significant elevation in CFU-F cells, CFU-F(Alk)(Phos+) cells (osteoprogenitors), and a higher percentage of CFU-F(Alk)(Phos+) cells/CFU-F cells consistent with an increase in CD45-/CD146+/CD105+/nestin+ mesenchymal stem cell frequency. Null BM exhibited a 2-fold enhancement in CD8+ T cells known to support osteoprogenitor differentiation and a 1.6-fold increase in CFU-GM colonies (osteoclast progenitors). We propose that Nmp4/CIZ limits the PTH anabolic window by restricting the number of BM stem, progenitor, and blood cells that support anabolic bone remodeling. PMID:22873745

He, Yongzheng; Childress, Paul; Hood, Mark; Alvarez, Marta; Kacena, Melissa A; Hanlon, Michael; McKee, Bryce; Bidwell, Joseph P; Yang, Feng-Chun

2013-02-01

191

Fibroblast Growth Factor 23, but not Parathyroid Hormone, Is Associated With Urinary Phosphate Regulation in Patients on Peritoneal Dialysis.  

PubMed

Fibroblast growth factor (FGF) 23 plays an important role in regulation of renal phosphate excretion in patients with chronic kidney disease. However, it remains undetermined whether FGF23 is closely linked to renal phosphate handling in patients with low glomerular filtration rate (GFR). The present cross-sectional study included 52 outpatients undergoing peritoneal dialysis with urine volume???100?mL/day. The primary outcome was level of urinary phosphate excretion, and the secondary outcomes were tubular maximal reabsorption of phosphate normalized to GFR (TmP/GFR), an index of the renal threshold for phosphate excretion, and level of peritoneal phosphate excretion. Variates of interest were serum FGF23 and parathyroid hormone (PTH) levels. The median and interquartile range of serum FGF23 level, TmP/GFR, and total urinary and peritoneal phosphate excretion were 5610 (1493-11?430) ng/mL, 1.30 (0.44-1.86) mg/dL, 117 (40-234) mg/day, and 208 (156-250) mg/day, respectively. Multivariate linear regression analysis revealed that serum FGF23 level was significantly (P?

Yamada, Shunsuke; Tsuruya, Kazuhiko; Tokumoto, Masanori; Yoshida, Hisako; Hasegawa, Shoko; Tanaka, Shigeru; Eriguchi, Masahiro; Nakano, Toshiaki; Masutani, Kosuke; Ooboshi, Hiroaki; Kitazono, Takanari

2015-02-01

192

A novel, mild, specific and indirect maleimido-based radioiodolabeling method. Radiolabeling of analogs derived from parathyroid hormone (PTH) and PTH-related protein (PTHrP).  

PubMed

In an effort to design a mild, non-oxidative and site-specific means of radiolabeling bioactive molecules we have employed maleimido-sulfhydryl chemistry to produce bioactive hormone radioligands. We have prepared two novel radioiodolabeled reagents, 3'-maleimidopropanoyl-3-125I-tyramide and its retro analog, N-maleoyl-N'-3-(4-hydroxy-3-125I-phenyl)propanoyl ethylenediamide, by either oxidative radioiodination of the precursors or radiolabeling of the phenolic component prior to its incorporation into the radiolabeling reagents. These reagents were then used to radiolabel analogs of parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) in an efficient way, yielding reaction mixtures which were easily purified. The radioligands obtained are stable upon storage and bind in a reversible manner to a single population of binding sites displaying affinity in the low nanomolar range. The potencies of these analogs are comparable to the non-modified PTH and PTHrP analogs. This study demonstrates the utility of the novel maleimido-based indirect radioiodination approach and highlights some of its advantages over either direct oxidative procedures or acylation using the Bolton-Hunter reagent. PMID:1336486

Chorev, M; Caulfield, M P; Roubini, E; McKee, R L; Gibbons, S W; Leu, C T; Levy, J J; Rosenblatt, M

1992-11-01

193

The Parathyroid  

Microsoft Academic Search

\\u000a Parathyroid diseases that are clinically significant range from hyperplastic glands causing hyperparathyroidism to parathyroid\\u000a adenomas and carcinomas. Parathyroid hyperplasia can involve primary or secondary disease and tertiary hyperparathyroidism\\u000a from chronic renal disease and other conditions. Parathyroid adenomas constitute the major cause of primary hyperparathyroidism\\u000a while parathyroid carcinomas are uncommon. Some patients with familial diseases may develop hyperparathyroidism or hypoparathyroidism.\\u000a Some

H. Rubén Harach

194

Vitamins  

MedlinePLUS

... and folate) Vitamin C Vitamin D Vitamin E Vitamin K You can usually get all your vitamins from ... foods you eat. Your body can also make vitamins D and K. People who eat a vegetarian diet may need ...

195

[Parathyroid gland autotransplantation: long-term results and direct test of the function of the implant by selective parathyroid hormone determination and stress test].  

PubMed

The precision of PTH measurement and the location of the implant allow the functioning of the transplanted tissue to be easily checked by separately measuring the PTH concentration in the arm bearing the transplant in comparison with the other side. In 10 of the 13 patients operated on by us it was observed that the transplant had grown and was functioning satisfactorily. In 2 further patients, in whom the PTH concentration alone gave no clear information on the functioning of the transplanted tissue, the tolerance test was for this purpose decisive. In fact the transplanted parathyroid tissue showed a rapid and clear response to pharmacodynamic stimulus, which demonstrated the viability of the transplant. We therefore venture to say that pharmacodynamic investigation is of a certain use in postoperative examinations of these patients, especially in doubtful cases. Unfortunately we have had no opportunity to perform a histological investigation of the implanted endocrine tissue, but this has already been reported on in print. PMID:7102134

Carmignani, G; Belgrano, E; Puppo, P; Repetto, U; Giuliani, L

1982-04-01

196

Human parathyroid hormone-(1-38) restores cancellous bone to the immobilized, osteopenic proximal tibial metaphysis in rats  

NASA Technical Reports Server (NTRS)

The purpose of this study was to determine if human parathyroid hormone-(1-38) (PTH) can restore cancellous bone mass to the established osteopenic, immobilized proximal tibial metaphyses (PTM) of female rats. The right hindlimbs of six-month-old female Sprague-Dawley rats were immobilized by bandaging the right hindlimbs to the abdomen. After 30 days of right hindlimb immobilization (RHLI), the rats were subcutaneously injected with 200 microgram hPTH(1-38)/kg/day for 15 (short-term) or 75 (longer-term) days. Static bone histomorphometry was performed on the primary spongiosa, while both static and dynamic histomorphometry were performed on the secondary spongiosa of the right PTM. Immobilization for 30 days without treatment decreased trabecular bone area, number and thickness in both primary and secondary spongiosa, and induced an increase in eroded perimeter and a decrease in tissue referent-bone formation rate (BFR/TV) in the secondary spongios. These changes reached a new steady state thereafter. Treatment with 200 microgram hPTH(1-38)/kg/day for 15 days, beginning at 30 days post immobilization (IM), significantly increased trabecular bone area, thickness and number in both primary and secondary spongiosa despite continuous IM when compared to the age-related and IM controls. The short-term (15 days) PTH treatment significantly increased labeling perimeter, mineral apposition rate and BFR/TV in the secondary spongiosa and stimulated longitudinal bone growth as compared to the age-related and IM controls. PTH treatment for longer-term (75 days) further increased trabecular bone area, thickness and number as compared to aging and IM controls and short-term (15 days) PTH treated groups. The bone formation indices in the secondary spongiosa of these longer-term treated rats were lower than that of short-term (15 days) PTH treated group, but they were still higher than those of IM and age-related controls. Our findings indicate that PTH treatment stimulates cancellous bone formation, restores and adds extra cancellous bone to the established, disuse-osteopenic proximal tibial metaphysis of continuously RHLI female rats. These results suggest that PTH may be a useful agent in treatment disuse-induced osteoporosis in humans.

Ma, Y. F.; Jee, W. S. S.; Ke, H. Z.; Lin, B. Y.; Liang, X. G.; Li, M.; Yamamoto, N.

1994-01-01

197

Enhanced Individual Trabecular Repair and Its Mechanical Implications in Parathyroid Hormone and Alendronate Treated Rat Tibial Bone.  

PubMed

Combined parathyroid hormone (PTH) and bisphosphonate (alendronate-ALN) therapy has recently been shown to increase bone volume fraction and plate-like trabecular structure beyond either monotherapy. To identify the mechanism through which plate-like structure was enhanced, we used in vivo microcomputed tomography (?CT) of the proximal tibia metaphysis and individual trabecular dynamics (ITD) analysis to quantify connectivity repair (incidences of rod connection and plate perforation filling) and deterioration (incidences of rod disconnection and plate perforation). Three-month-old female, intact rats were scanned before and after a 12 day treatment period of vehicle (Veh, n?=?5), ALN (n?=?6), PTH (n?=?6), and combined (PTH+ALN, n?=?6) therapy. Additionally, we used computational simulation and finite element (FE) analysis to delineate the contributions of connectivity repair or trabecular thickening to trabecular bone stiffness. Our results showed that the combined therapy group had greater connectivity repair (5.8?±?0.5% connected rods and 2.0?±?0.3% filled plates) beyond that of the Veh group, resulting in the greatest net gain in connectivity. For all treatment groups, increases in bone volume due to thickening (5-31%) were far greater than those due to connectivity repair (2-3%). Newly formed bone contributing only to trabecular thickening caused a 10%, 41%, and 69% increase in stiffness in the ALN, PTH, and PTH+ALN groups, respectively. Moreover, newly formed bone that led to connectivity repair resulted in an additional improvement in stiffness, with the highest in PTH+ALN (by an additional 12%), which was significantly greater than either PTH (5.6%) or ALN (4.5%). An efficiency ratio was calculated as the mean percent increase in stiffness divided by mean percent increase in BV for either thickening or connectivity repair in each treatment. For all treatments, the efficiency ratio of connectivity repair (ALN: 2.9; PTH: 3.4; PTH+ALN: 4.4) was higher than that due to thickening (ALN: 2.0; PTH: 1.7; PTH+ALN: 2.2), suggesting connectivity repair required less new bone formation to induce larger gains in stiffness. We conclude that through rod connection and plate perforation filling PTH+ALN combination therapy improved bone stiffness in a more efficient and effective manner than either monotherapy. PMID:25321622

Altman, Allison R; de Bakker, Chantal M J; Tseng, Wei-Ju; Chandra, Abhishek; Qin, Ling; Sherry Liu, X

2015-01-01

198

Parathyroid hormone is a plausible mediator for the metabolic syndrome in the morbidly obese: a cross-sectional study  

PubMed Central

Background The biological mechanisms in the association between the metabolic syndrome (MS) and various biomarkers, such as 25-hydroxyvitamin D (vit D) and magnesium, are not fully understood. Several of the proposed predictors of MS are also possible predictors of parathyroid hormone (PTH). We aimed to explore whether PTH is a possible mediator between MS and various possible explanatory variables in morbidly obese patients. Methods Fasting serum levels of PTH, vit D and magnesium were assessed in a cross-sectional study of 1,017 consecutive morbidly obese patients (68% women). Dependencies between MS and a total of seven possible explanatory variables as suggested in the literature, including PTH, vit D and magnesium, were specified in a path diagram, including both direct and indirect effects. Possible gender differences were also included. Effects were estimated using Bayesian path analysis, a multivariable regression technique, and expressed using standardized regression coefficients. Results Sixty-eight percent of the patients had MS. In addition to type 2 diabetes and age, both PTH and serum phosphate had significant direct effects on MS; 0.36 (95% Credibility Interval (CrI) [0.15, 0.57]) and 0.28 (95% CrI [0.10,0.47]), respectively. However, due to significant gender differences, an increase in either PTH or phosphate corresponded to an increased OR for MS in women only. All proposed predictors of MS had significant direct effects on PTH, with vit D and phosphate the strongest; -0.27 (95% CrI [-0.33,-0.21]) and -0.26 (95% CrI [-0.32,-0.20]), respectively. Though neither vit D nor magnesium had significant direct effects on MS, for women they both affected MS indirectly, due to the strong direct effect of PTH on MS. For phosphate, the indirect effect on MS, mediated through serum calcium and PTH, had opposite sign than the direct effect, resulting in the total effect on MS being somewhat attenuated compared to the direct effect only. Conclusion Our results indicate that for women PTH is a plausible mediator in the association between MS and a range of explanatory variables, including vit D, magnesium and phosphate. PMID:21306649

2011-01-01

199

The Calcium-Sensing Receptor Mediates Bone Turnover Induced by Dietary Calcium and Parathyroid Hormone in Neonates  

PubMed Central

We have investigated, in neonates, whether the calcium-sensing receptor (CaR) mediates the effects of dietary calcium on bone turnover and/or modulates parathyroid hormone (PTH)–induced bone turnover. Wild-type (WT) pups and pups with targeted deletion of the Pth (Pth–/–) gene or of both Pth and CaR (Pth–/–CaR–/–) genes were nursed by dams on a normal or high-calcium diet. Pups nursed by dams on a normal diet received daily injections of vehicle or of PTH(1–34) (80 µg/kg) for 2 weeks starting from 1 week of age. In pups receiving vehicle and fed by dams on a normal diet, trabecular bone volume, osteoblast number, type 1 collagen–positive area, and mineral apposition rate, as well as the expression of bone-formation-related genes, all were reduced significantly in Pth–/– pups compared with WT pups and were decreased even more dramatically in Pth–/–CaR–/– pups. These parameters were increased in WT and Pth–/– pups but not in Pth–/–CaR–/– pups fed by dams on a high-calcium diet compared with pups fed by dams on a normal diet. These parameters also were increased in WT, Pth–/–, and Pth–/–CaR–/– pups following exogenous PTH treatment; however, the percentage increase was less in Pth–/–CaR–/– pups than in WT and Pth–/– pups. In vehicle-treated pups fed by dams on either the normal or high-calcium diet and in PTH-treated pups fed by dams on a normal diet, the number and surfaces of osteoclasts and the ratio of RANKL/OPG were reduced significantly in Pth–/– pups and less significantly in Pth–/–CaR–/– pups compared with WT pups. These parameters were further reduced significantly in WT and Pth–/– pups from dams fed a high-calcium diet but did not decrease significantly in similarly treated Pth–/–CaR–/– pups, and they increased significantly in PTH-treated pups compared with vehicle-treated, genotype-matched pups fed by dams on the normal diet. These results indicate that in neonates, the CaR mediates alterations in bone turnover in response to changes in dietary calcium and modulates PTH-stimulated bone turnover. © 2011 American Society for Bone and Mineral Research. PMID:21542007

Shu, Lei; Ji, Ji; Zhu, Qi; Cao, Guofan; Karaplis, Andrew; Pollak, Martin R; Brown, Edward; Goltzman, David; Miao, Dengshun

2011-01-01

200

Protein intake, control of serum phosphorus, and relatively low levels of parathyroid hormone in elderly hemodialysis patients.  

PubMed

In maintenance hemodialysis (MHD) patients, advanced age is a factor associated with relative hypoparathyroidism and an adynamic bone. However, the underlying mechanism remains elusive. The aim of the present study was to analyze whether the observed spontaneous decrease in protein intake in the elderly favors a better control of serum phosphorus (P) and parathyroid hormone (PTH) levels. A cross-sectional study including 207 MHD patients (mean age, 60 +/- 14; 59% males; time on dialysis, 61 +/- 55 months) dialyzed 3.5 to 4.5 hours 3 times a week using bicarbonate hemodialysis from 6 Spanish hemodialysis centers was performed. In 95 patients, the nutrient intake was recorded over a 5-day period, and average daily ingestion of nutrients was calculated using a computerized diet analysis system. One-way analysis of variance showed that serum phosphorus and intact PTH decreased with age. In addition, patients with serum phosphorus lower than 4 mg/dL as compared with those with serum phosphorus greater than 4 mg/dL were older (68 +/- 9 v 58 +/- 15 years, P < 0.001), had a lower protein (0.86 +/- 0.3 v 1.05 +/- 0.4 g/kg body weight, P < 0.01) and caloric intake (21.9 +/- 7.4 v 25.7 +/- 8.3 kcal/Kg body weight, P < 0.01), and had lower PTH levels (102 +/- 155 v 290 +/- 345 pg/mL, P < 0.001). An inverse and significant correlation was observed between age and protein intake (r = -0.48; P < 0.01), caloric intake (r = -0.37, P < 0.01), serum phosphorus concentration (r = -0.40; P < 0.01), and PTH levels (r = -0.26; P < 0.01). Additionally, a significant positive correlation was found between serum phosphorus and PTH levels (r = 0.40; P < 0.01). The results obtained in the present study suggest that a lower serum phosphorus level due to spontaneous reduction of protein intake might contribute to the relative low PTH levels observed in elderly hemodialysis patients. PMID:11382697

Lorenzo, V; Martín, M; Rufino, M; Jiménez, A; Malo, A M; Sanchez, E; Hernández, D; Rodríguez, M; Torres, A

2001-06-01

201

Expression of parathyroid-specific genes in vascular endothelial progenitors of normal and tumoral parathyroid glands.  

PubMed

Parathyroid tissue is able to spontaneously induce angiogenesis, proliferate, and secrete parathyroid hormone when autotransplanted in patients undergoing total parathyroidectomy. Angiogenesis is also involved in parathyroid tumorigenesis. Here we investigated the anatomical and molecular relationship between endothelial and parathyroid cells within human parathyroid glands. Immunohistochemistry for CD34 antigen identified two subpopulations in normal and tumoral parathyroid glands: one constituted by cells lining small vessels that displayed endothelial antigens (factor VIII, isolectin, laminin, CD146) and the other constituted of single cells scattered throughout the parenchyma that did not express endothelial markers. These parathyroid-derived CD34(+) cells were negative for the hematopoietic and mesenchymal markers CD45, Thy-1/CD90, CD105, and CD117/c-kit; however, a subset of CD34(+) cells co-expressed the parathyroid specific genes glial cell missing B, parathyroid hormone, and calcium sensing receptor. When cultured, these cells released significant amount of parathyroid hormone. Parathyroid-derived CD34(+) cells, but not CD34(-) cells, proliferated slowly and differentiated into mature endothelial cells. CD34(+) cells from parathyroid tumors differed from those derived from normal parathyroid glands as: 1) they were more abundant and mainly scattered throughout the parenchyma; 2) they rarely co-expressed CD146; and 3) a fraction co-expressed nestin. In conclusion, we identified cells expressing endothelial and parathyroid markers in human adult parathyroid glands. These parathyroid/endothelial cells were more abundant and less committed in parathyroid tumors compared with normal glands, showing features of endothelial progenitors, which suggests that they might be involved in parathyroid tumorigenesis. PMID:19644013

Corbetta, Sabrina; Belicchi, Marzia; Pisati, Federica; Meregalli, Mirella; Eller-Vainicher, Cristina; Vicentini, Leonardo; Beck-Peccoz, Paolo; Spada, Anna; Torrente, Yvan

2009-09-01

202

Association of serum inorganic phosphate with sex steroid hormones and vitamin D in a nationally representative sample of men  

PubMed Central

SUMMARY Defects in bone regulatory pathways have been linked to chronic diseases including cardiovascular disease and cancer. In men, a link between bone metabolism and gonadal hormones has been suggested. However, to date, there is lack of evidence on the association between serum inorganic phosphate (Pi) and sex steroid hormones. The objective of this study was to investigate the association between Pi, sex steroid hormones and a known Pi metabolic regulator, vitamin D, in men in the National Health and Nutrition Examination Survey III (NHANES III). From NHANES III, we selected 1412 men aged 20+ who participated in the morning session of Phase I (1988–1991) with serum measurements of Pi, sex hormones, and vitamin D. Multivariable linear regression was used to calculate crude and geometric mean Pi by total and estimated free testosterone and estradiol, sex hormone-binding globulin, androstanediol glucuronide (AAG), and vitamin D. Similar analyses were performed while stratifying by race/ethnicity and vitamin D levels. We found a lack of statistically significant difference in geometric means of Pi across quintiles of concentrations of sex hormones, indicating a tight regulation of Pi. However, Pi levels were inversely associated with calculated free testosterone in non-Hispanic black men, with geometric mean levels of Pi of 1.16 and 1.02 ng/mL for those in the lowest and highest quintiles of free testosterone, respectively (p-trend < 0.05). A similar but weaker pattern was seen between total testosterone and Pi. An inverse association was also seen between AAG and Pi in men with vitamin D concentration below the median (<24.2 ng/mL). No associations were observed among men with vitamin D levels at or above the median. Our findings suggest a weak link among sex hormones, vitamin D, and Pi in men. The observed effects of race/ethnicity and vitamin D indicate a complex association involving various regulators of Pi homeostasis. PMID:25270590

Wulaningsih, W.; Van Hemelrijck, M.; Michaelsson, K.; Kanarek, N.; Nelson, W. G.; Ix, J. H.; Platz, E. A.; Rohrmann, S.

2015-01-01

203

Association of serum inorganic phosphate with sex steroid hormones and vitamin D in a nationally representative sample of men.  

PubMed

Defects in bone regulatory pathways have been linked to chronic diseases including cardiovascular disease and cancer. In men, a link between bone metabolism and gonadal hormones has been suggested. However, to date, there is lack of evidence on the association between serum inorganic phosphate (Pi) and sex steroid hormones. The objective of this study was to investigate the association between Pi, sex steroid hormones and a known Pi metabolic regulator, vitamin D, in men in the National Health and Nutrition Examination Survey III (NHANES III). From NHANES III, we selected 1412 men aged 20+ who participated in the morning session of Phase I (1988-1991) with serum measurements of Pi, sex hormones, and vitamin D. Multivariable linear regression was used to calculate crude and geometric mean Pi by total and estimated free testosterone and estradiol, sex hormone-binding globulin, androstanediol glucuronide (AAG), and vitamin D. Similar analyses were performed while stratifying by race/ethnicity and vitamin D levels. We found a lack of statistically significant difference in geometric means of Pi across quintiles of concentrations of sex hormones, indicating a tight regulation of Pi. However, Pi levels were inversely associated with calculated free testosterone in non-Hispanic black men, with geometric mean levels of Pi of 1.16 and 1.02 ng/mL for those in the lowest and highest quintiles of free testosterone, respectively (p-trend < 0.05). A similar but weaker pattern was seen between total testosterone and Pi. An inverse association was also seen between AAG and Pi in men with vitamin D concentration below the median (<24.2 ng/mL). No associations were observed among men with vitamin D levels at or above the median. Our findings suggest a weak link among sex hormones, vitamin D, and Pi in men. The observed effects of race/ethnicity and vitamin D indicate a complex association involving various regulators of Pi homeostasis. PMID:25270590

Wulaningsih, W; Van Hemelrijck, M; Michaelsson, K; Kanarek, N; Nelson, W G; Ix, J H; Platz, E A; Rohrmann, S

2014-11-01

204

The influence of pyrophosphate, condensed phosphates, phosphonates and other phosphate compounds on the dissolution of hydroxyapatite in vitro and on bone resorption induced by parathyroid hormone in tissue culture and in thyroparathyroidectomised rats  

Microsoft Academic Search

Earlier studies have shown that inorganic pyrophosphate (PPi) inhibits the dissolution of hydroxyapatite crystalsin vitro and it has been suggested that PPi might be a physiological regulator of bone resorption. In this study PP1 and other phosphate compounds have been tested for their ability to inhibit bone resorption induced by parathyroid hormone in mouse calvaria and to inhibit the rise

R. G. G. Russell; R. C. Mühlbauer; S. Bisaz; D. A. Williams; H. Fleisch

1970-01-01

205

Clinical and Molecular Genetics of Parathyroid Neoplasms  

PubMed Central

Primary hyperparathyroidism (HPT) results from the excessive secretion of parathyroid hormone from parathyroid tumors. While most HPT is sporadic, it is associated with a familial syndrome in a minority of cases. Study of these syndromes has helped define the pathophysiology of both familial and sporadic parathyroid neoplasms. Investigation of kindreds with multiple endocrine neoplasia type 1 (MEN1) and the hyperparathyroidism-jaw tumor syndrome led to the discovery of the tumor suppressor genes MEN1 and HRPT2. We now recognize that somatic mutations in MEN1 and HRPT2 tumor suppressor genes are frequent events in sporadic parathyroid adenomas and carcinomas, respectively. Parathyroid tumors in the MEN2A syndrome result from mutational activation of the RET oncogene. The CCND1/PRAD1 oncogene was discovered by analysis of sporadic parathyroid tumors. Studies of familial isolated hyperparathyroidism and analysis of chromosomal loss and gain in parathyroid tumors suggest that other genes relevant to parathyroid neoplasia await identification. PMID:20833339

Sharretts, John M.; Simonds, William F.

2010-01-01

206

Crystallization of the receptor-binding domain of parathyroid hormone-related protein in complex with a neutralizing monoclonal antibody Fab fragment  

SciTech Connect

Parathyroid hormone-related protein (PTHrP) plays an important role in regulating embryonic skeletal development and is abnormally regulated in the pathogenesis of skeletal complications observed with many cancers and osteoporosis. It exerts its action through binding to a G-protein-coupled seven-transmembrane cell-surface receptor (GPCR). Structurally, GPCRs are very difficult to study by X-ray crystallography. In this study, a monoclonal antibody Fab fragment which recognizes the same region of PTHrP as its receptor, PTH1R, was used to aid in the crystallization of PTHrP. The resultant protein complex was crystallized using the hanging-drop vapour-diffusion method with polyethylene glycol as a precipitant. The crystals belonged to the orthorhombic space group P2{sub 1}2{sub 1}2, with unit-cell parameters a = 72.6, b = 96.3, c = 88.5 {angstrom}, and diffracted to 2.0 {angstrom} resolution using synchrotron radiation. The crystal structure will shed light on the nature of the key residues of PTHrP that interact with the antibody and will provide insights into how the antibody is able to discriminate between PTHrP and the related molecule parathyroid homone.

McKinstry, William J.; Polekhina, Galina; Diefenbach-Jagger, Hannelore; Sato, Koh; Onuma, Etsuro; Gillespie, Matthew T.; Martin, Thomas J.; Parker, Michael W.; (SVIMR-A); (Chugai); (Melbourne)

2009-04-01

207

Low Vitamin D Status in Mother-Newborn Pairs in Greece  

Microsoft Academic Search

Adequate vitamin D status during pregnancy is crucial to assure normal fetal skeletal growth and to provide the vitamin D\\u000a needed for infants’ stores. To determine the actual situation in Greece, we evaluated serum 25-hydroxyvitamin D (25[OH]D),\\u000a calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), parathyroid hormone (PTH), osteocalcin (OC), and calcitonin (CT)\\u000a concentrations in 123 healthy mother-newborn pairs recruited from

P. Nicolaidou; Z. Hatzistamatiou; A. Papadopoulou; J. Kaleyias; E. Floropoulou; E. Lagona; V. Tsagris; C. Costalos; A. Antsaklis

2006-01-01

208

Mode of action of parathyroid hormone and cyclic adenosine 3?,5?-monophosphate on renal tubular phosphate reabsorption in the dog  

PubMed Central

To evaluate the effects of parathyroid hormone and cyclic adenosine monophosphate on proximal tubular sodium and phosphate reabsorption, micropuncture studies were performed on dogs that received a highly purified preparation of parathyroid hormone (PTH), dibutyryl cyclic 3?,5?-adenosine monophosphate (cyclic AMP), 5?-AMP, and saline. PTH resulted in a 30-40% inhibition of sodium and phosphate reabsorption in the proximal tubule unassociated with a rise in either total kidney or single nephron glomerular filtration rate (GFR). The bulk of the phosphate rejected proximally was excreted in the final urine while sodium excretion rose minimally despite the marked proximal inhibition, consistent with the presence of reabsorptive sites in the distal nephron for sodium but not phosphate. The infusion of dibutyryl cyclic AMP either systemically or directly into the renal artery inhibited proximal sodium and phosphate reabsorption in the absence of changes in either total kidney or single nephron GFR, resembling the effects of PTH quantitatively and qualitatively. In contrast, another adenine nucleotide, 5?-AMP, did not inhibit the reabsorption of either sodium or phosphate. These observations support the thesis that renal effects of PTH are mediated via stimulation of renal cortical adenyl cyclase. The infusion of a moderate saline load, 25 ml/kg, also produced a similar inhibition of proximal tubular fractional sodium and phosphate reabsorption with a marked phosphaturia but only minimal natriuresis. Thus, changes in sodium and phosphate reabsorption occur in parallel in the proximal tubule when sodium reabsorption is inhibited either with volume expansion or with administration of “specific” phosphaturic agents such as PTH or cyclic AMP. These data are consistent with the thesis that phosphate reabsorption is dependent upon proximal tubular sodium reabsorption wherein the phosphaturic effect of PTH might be the result of a primary inhibition of proximal tubular sodium reabsorption mediated by adenyl cyclase stimulation. PMID:4322720

Agus, Zalman S.; Puschett, Jules B.; Senesky, Dorothy; Goldberg, Martin

1971-01-01

209

The influence of smoking on vitamin D status and calcium metabolism  

Microsoft Academic Search

Objective: To assess the influence of smoking on serum parathyroid hormone (PTH), serum vitamin D metabolites, serum ionized calcium, serum phosphate, and biochemical markers of bone turnover in a cohort of 510 healthy Danish perimenopausal women.Design: A cross-sectional study.Setting: Copenhagen, Denmark.Subjects: Five-hundred-and-ten healthy women aged 45–58 y, included 3–24 months after last menstrual bleeding. None were using hormone replacement therapy.Methods:

C Brot; N Rye Jørgensen; O Helmer Sørensen

1999-01-01

210

Vitamin D status before and after hypophysectomy in dogs with pituitary-dependent hypercortisolism.  

PubMed

Both spontaneous hypercortisolism and chronic glucocorticoid treatment are associated with osteoporosis and low circulating concentrations of 1,25-dihydroxy-vitamin D in humans. Pituitary-dependent hypercortisolism (PDH) is a common disorder in dogs, but little is known about the vitamin D status of affected dogs. Pituitary-dependent hypercortisolism in dogs can be treated effectively by hypophysectomy and subsequent hormone supplementation. Because hormone supplementation does not include GH, dogs that have undergone hypophysectomy have low circulating concentrations of GH and IGF-1, which may result in low plasma 1,25-dihydroxy-vitamin D concentrations and consequently increased parathyroid hormone secretion. The aim of this study was to determine whether dogs with PDH need vitamin D supplementation before and/or after hypophysectomy. To this end, we measured plasma concentrations of GH, IGF-1, parathyroid hormone, calcium, phosphate, and vitamin D metabolites in 12 dogs with PDH before and 8 wk after hypophysectomy and in 12 control dogs. Although plasma GH concentrations were lower in dogs with PDH than in control dogs both before and after hypophysectomy, the vitamin D status was similar. In conclusion, there is no need for vitamin D supplementation in dogs with PDH, either before or after hypophysectomy. PMID:22032856

Corbee, R J; Tryfonidou, M A; Meij, B P; Kooistra, H S; Hazewinkel, H A W

2012-01-01

211

Minimally invasive parathyroid surgery.  

PubMed

More surgeons are performing unilateral exploration for primary hyperparathyroidism (HPT) than ever before. This article reviews the factors that have led to the trend toward less invasive surgery. Discussion includes the history of unilateral exploration for HPT, the advent of magnetic resonance sestamibi imaging, and the development of intraoperative assays for parathyroid hormone. Results of minimally invasive techniques, including radio-guided parathyroidectomy, endoscopic parathyroidectomy, and outpatient parathyroidectomy, also are presented. PMID:11059711

Howe, J R

2000-10-01

212

Extracellular Calcium-Sensing Receptor (CaR) Expression and Its Potential Role in Parathyroid Hormone-Related Peptide (PTHrP) Secretion in the H-500 Rat Leydig Cell Model of Humoral Hypercalcemia of Malignancy  

Microsoft Academic Search

Humoral hypercalcemia of malignancy (HHM) occurs when secretion of parathyroid hormone-related peptide (PTHrP) by cancer cells causes hypercalcemia in the absence of skeletal metastases. High extracellular calcium (Ca2+o) increases secretion of PTH-like bioactivity by rat H-500 leydig cells, a transplantable model of HHM, an action potentially mediated by the Ca2+o-sensing receptor (CaR). In this study we investigated whether H-500 cells

Jennifer L. Sanders; Naibedya Chattopadhyay; Olga Kifor; Toru Yamaguchi; Edward M. Brown

2000-01-01

213

Study of Menopausal Women with Heart Disease Finds No Benefit, Potential for Harm from Hormone Therapy and Antioxidant Vitamins  

NSDL National Science Digital Library

This site describes a study sponsored by the National Heart, Lung, and Blood Institute, which found that postmenopausal women with heart disease did not benefit from high doses of antioxidants vitamins, whether alone or in combination with hormone replacement therapy. In fact, researchers found both treatments to be potentially harmful.

2002-01-01

214

Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: Results of the study to evaluate early kidney disease  

Microsoft Academic Search

Abnormalities of mineral metabolism occur early in chronic kidney disease. Quantification of the prevalence of these abnormalities has not been described using current assays nor in large unselected populations. This outpatient cohort cross-sectional study was conducted in 153 centers, (71% primary care practices). Blood for parathyroid hormone (PTH), vitamin D metabolites, creatinine, calcium (Ca), and phosphorus (P) were drawn between

A Levin; G L Bakris; M Molitch; M Smulders; J Tian; L A Williams; D L Andress

2007-01-01

215

Vitamin D requirements: current and future.  

PubMed

The requirements for vitamin D were last set in 1997 by the Food and Nutrition Board of the Institute of Medicine. Intakes were assumed to come from diet, and values were based on achievement of adequate vitamin D status and on observed values to prevent seasonal variations in parathyroid hormone concentrations. Serum 25-hydroxyvitamin D concentrations were considered the best indicator of vitamin D adequacy, because the production of 25-hydroxyvitamin D is not regulated. Normal ranges were obtained from reference populations, but the values varied widely with age and geographic region. Revised recommendations should take into consideration appropriate functional measures for multiple tissues and disease risks. Vitamin D-calcium interdependencies must be taken into account. Higher intakes of both vitamin D and calcium can reduce bone resorption, and higher concentrations of one nutrient might compensate for insufficiency in the other. Better ways to assess vitamin D (and calcium) inputs are needed. Food composition databases are incomplete for both vitamin D and calcium, especially in this era of food fortification, and are complicated by the poor quality control for vitamin D fortification. Upper levels of vitamin D intake were set at 50 microg/d (2000 IU/d) for all ages. Some individuals would require higher levels than these to achieve serum 25-hydroxyvitamin D concentrations for optimal calcium absorption. So much new information on vitamin D and health has been collected since the requirements were set in 1997 that this nutrient is likely the most in need of revised requirements. PMID:15585797

Weaver, Connie M; Fleet, James C

2004-12-01

216

Amphibian parathyroids: morphological and functional aspects.  

PubMed

Amphibians living partially or totally in a terrestrial environment are the first tetrapods to possess parathyroid glands. Purely aquatic amphibians and amphibian larvae lack these endocrine glands. The parathyroids develop at the time of metamorphosis. The parathyroid glands in caecilians consist of a single cell type, that of urodeles may be composed of basal (supporting) cells and suprabasal (chief) cells, and that of anurans of small and large chief cells. Parathyroid glands of caecilians and anurans lack connective tissue, blood vessels, and nerves. The parathyroid cells become activated in response to decreased blood calcium concentration and undergo changes indicating increased parathyroid hormone secretion. Increased blood calcium concentration suppresses secretory activity. Usually, parathyroidectomy elicits hypocalcemia in most amphibians. Such operations have no effect in lower urodeles. Parathyroid hormone administration provokes hypercalcemia in most amphibians. The parathyroids of caecilians have not been studied in detail. The urodeles and anurans exhibit seasonal changes in the parathyroid glands. These changes may be initiated by environmental stimuli such as light, temperature, or alterations in blood calcium levels caused by natural hibernation. PMID:8580512

Srivastav, A K; Das, V K; Das, S; Sasayama, Y; Suzuki, N

1995-10-01

217

Cleavage of the ER-targeting signal sequence of parathyroid hormone-related protein is cell-type-specific and regulated in Cis by its nuclear localization signal.  

PubMed

Prepro-parathyroid hormone-related protein (ppPTHrP) has two targeting signals, an N-terminal signal sequence and a nuclear localization signal (NLS). In fact, the protein is not only secreted from the cell but also found in the nucleus and/or nucleolus. In order to understand the function of the PTHrP signal sequence for the dual localization, the signal sequence cleavage of a series of ppPTHrP deletion mutants fused to Escherichia coli leader peptidase was analysed in vitro and in several cell lines. Efficiency of the PTHrP signal sequence cleavage was intrinsically low in the in vitro reconstitution system. In cultured cells, cleavage efficiency of the PTHrP signal sequence varied significantly, being lowest in COS-1 cells, but rising in HeLa, HEK293 and CV-1 cells. However, virtually complete signal sequence cleavage was observed in CHO cells. In addition, the NLS of PTHrP had a negative effect on its own signal sequence cleavage, which could be enhanced by deletion of the spacer sequence between the signal sequence and the NLS. There was a roughly inverse relationship between the signal sequence cleavage and the nuclear localization of PTHrP. Thus, the final destination of PTHrP could be regulated at the ER membrane. PMID:18211921

Amaya, Yoshihiro; Nakai, Toshiki; Komaru, Keiichi; Tsuneki, Masayuki; Miura, Satoshi

2008-04-01

218

The parathyroid hormone-responsive B1 gene is interrupted by a t(1;7)(q42;p15) breakpoint associated with Wilms' tumour.  

PubMed

Wilms' tumour (WT) has a diverse and complex molecular aetiology, with several different loci identified by cytogenetic and molecular analyses. One such locus is on chromosome 7p, where cytogenetic abnormalities and loss of heterozygosity (LOH) indicate the presence of a Wilms' tumour suppressor gene. In order to isolate a candidate gene for this locus, we have characterized the breakpoint regions at a novel constitutional chromosome translocation (t(1;7)(q42;p15)), found in a child with WT and skeletal abnormalities. We identified two genes that were interrupted by the translocation: the parathyroid hormone-responsive B1 gene (PTH-B1) at 7p and obscurin at 1q. With no evidence for LOH at 1q42, we focused on the characterization of PTH-B1. We detected novel alternately spliced isoforms of PTH-B1, which were expressed in a wide range of adult and foetal tissues. Importantly, expression of two isoforms were disrupted in the WT of the t(1;7) patient. We also identified an additional splice isoform expressed only in 7p LOH tumours. The disruption of PTH-B1 by the t(1;7), together with aberrant splicing in sporadic WTs, suggests that PTH-B1 is a candidate for the 7p Wilms' tumour suppressor gene. PMID:12618763

Vernon, Ellen G; Malik, Karim; Reynolds, Paul; Powlesland, Rachel; Dallosso, Anthony R; Jackson, Sally; Henthorn, Karla; Green, Eric D; Brown, Keith W

2003-03-01

219

Calcium-dependent ligand binding and G-protein signaling of family B GPCR parathyroid hormone 1 receptor purified in nanodiscs.  

PubMed

GPCRs mediate intracellular signaling upon external stimuli, making them ideal drug targets. However, little is known about their activation mechanisms due to the difficulty in purification. Here, we introduce a method to purify GPCRs in nanodiscs, which incorporates GPCRs into lipid bilayers immediately after membrane solubilization, followed by single-step purification. Using this approach, we purified a family B GPCR, parathyroid hormone 1 receptor (PTH1R), which regulates calcium and phosphate homeostasis and is a drug target for osteoporosis. We demonstrated that the purified PTH1R in nanodiscs can bind to PTH(1-34) and activate G protein. We also observed that Ca(2+) is a weak agonist of PTH1R, and Ca(2+) in millimolar concentration can switch PTH(1-34) from an inverse agonist to an agonist. Hence, our results show that nanodiscs are a viable vehicle for GPCR purification, enabling studies of GPCRs under precise experimental conditions without interference from other cellular or membrane components. PMID:23237450

Mitra, Nivedita; Liu, Yuting; Liu, Jian; Serebryany, Eugene; Mooney, Victoria; DeVree, Brian T; Sunahara, Roger K; Yan, Elsa C Y

2013-03-15

220

Parathyroid Hormone (PTH)/PTH-related Peptide Type 1 Receptor (PPR) Signaling in Osteocytes Regulates Anabolic and Catabolic Skeletal Responses to PTH*  

PubMed Central

Parathyroid hormone (PTH) is the only Food and Drug Administration-approved anabolic agent to treat osteoporosis; however, the cellular targets of PTH action in bone remain controversial. PTH modulates bone turnover by binding to the PTH/PTH-related peptide (PTHrP) type 1 receptor (PPR), a G-protein-coupled receptor highly expressed in bone and kidneys. Osteocytes, the most abundant cells in adult bone, also express PPR. However, the physiological relevance of PPR signaling in osteocytes remains to be elucidated. Toward this goal, we generated mice with PPR deletion in osteocytes (Ocy-PPRKO). Skeletal analysis of these mice revealed a significant increase in bone mineral density and trabecular and cortical bone parameters. Osteoblast activities were reduced in these animals, as demonstrated by decreased collagen type I ?1 mRNA and receptor activator of NF-?B ligand (RANKL) expression. Importantly, when subjected to an anabolic or catabolic PTH regimen, Ocy-PPRKO animals demonstrated blunted skeletal responses. PTH failed to suppress SOST/Sclerostin or induce RANKL expression in Ocy-PPRKO animals compared with controls. In vitro, osteoclastogenesis was significantly impaired in Ocy-PPRKO upon PTH administration, indicating that osteocytes control osteoclast formation through a PPR-mediated mechanism. Taken together, these data indicate that PPR signaling in osteocytes is required for bone remodeling, and receptor signaling in osteocytes is needed for anabolic and catabolic skeletal responses. PMID:23729679

Saini, Vaibhav; Marengi, Dean A.; Barry, Kevin J.; Fulzele, Keertik S.; Heiden, Erica; Liu, Xiaolong; Dedic, Christopher; Maeda, Akira; Lotinun, Sutada; Baron, Roland; Pajevic, Paola Divieti

2013-01-01

221

Cyclic parathyroid hormone related protein antagonists: lysine 13 to aspartic acid 17 [i to (i + 4)] side chain to side chain lactamization.  

PubMed

Cyclization of parathyroid hormone related protein (7-34)amide [PTHrP(7-34)NH2] via covalent bond formation between the epsilon-amino of Lys13 and the beta-carboxyl of Asp17 yielded a 20-membered ring lactam. This analogue, [Lys13,Asp17]PTHrP(7-34)NH2, was 5-10-fold more potent than the linear parent peptide (Kb = 15 and 18 nM in PTH receptor binding assays, and Ki = 130 and 17 nM in PTH-stimulated adenylate cyclase assays in bovine renal cortical membrane and in human bone derived B10 cells, respectively). In contrast, a linear analogue in which charges in positions 13 and 17 were eliminated and other stereoisomers of the above-mentioned lactam in which either Lys13 and/or Asp17 were replaced by the corresponding D-amino acids were much less potent with regard to antagonist bioactivity than the parent peptide. The rationale for the design of the lactam as well as the conformational implications for the PTHrP sequence in light of reported models suggested for the 1-34 peptide are described. The potential use of conformationally constrained analogues for elucidating the "bioactive conformation" of antagonists and for the design of substantially simplified molecular structures for antagonists is discussed. PMID:1646005

Chorev, M; Roubini, E; McKee, R L; Gibbons, S W; Goldman, M E; Caulfield, M P; Rosenblatt, M

1991-06-18

222

Surgery for Primary Hyperparathyroidism in Patients with Preoperatively Negative Sestamibi Scan and Discordant Imaging Studies: The Usefulness of Intraoperative Parathyroid Hormone Monitoring  

PubMed Central

The aim of this study was to evaluate the impact of intraoperative parathyroid hormone (PTH) monitoring on surgical strategy, intraoperative findings, and outcome in patients with negative sestamibi scintigraphy and with discordant imaging studies. We divided our 175 patients into 3 groups: group A was methoxyisobutylisonitrile (MIBI)-positive and ultrasonography positive and was concordant (114 patients), group B was MIBI-positive and ultrasonography-negative (50 patients), and group C was MIBI—and ultrasonography-negative (11 patients). The overall operative success was 99.12% in group A, 98% in group B, and 90.91% in group C, with an incidence of multiglandular disease of 3.5% in group A, 12% in group B, and 9.09% in group C. Intraoperative PTH monitoring changed the operative management in 2.63% of patients in group A and 14% in group B. The use of intraoperative PTH achieves to obtain excellent results in the treatment of primary hyperparathyroidism in high-volume centers, even in the most difficult cases, during MIBI-negative and discordant preoperative imaging studies. PMID:24250241

Calò, Pietro Giorgio; Pisano, Giuseppe; Loi, Giulia; Medas, Fabio; Tatti, Alberto; Piras, Stefano; Nicolosi, Angelo

2013-01-01

223

Parathyroid hormone PTH(1–34) increases the volume, mineral content, and mechanical properties of regenerated mineralizing tissue after distraction osteogenesis in rabbits  

PubMed Central

Background and purpose Parathyroid hormone (PTH) has attracted considerable interest as a bone anabolic agent. Recently, it has been suggested that PTH can also enhance bone repair after fracture and distraction osteogenesis. We analyzed bone density and strength of the newly regenerated mineralized tissue after intermittent treatment with PTH in rabbits, which undergo Haversian bone remodeling similar to that in humans. Methods 72 New Zealand White rabbits underwent tibial mid-diaphyseal osteotomy and the callus was distracted 1 mm/day for 10 days. The rabbits were divided into 3 groups, which received injections of PTH 25 µg/kg/day for 30 days, saline for 10 days and PTH 25 µg/kg/day for 20 days, or saline for 30 days. At the end of the study, the rabbits were killed and the bone density was evaluated with DEXA. The mechanical bone strength was determined by use of a 3-point bending test. Results In the 2 PTH-treated groups the regenerate callus ultimate load was 33% and 30% higher, absorbed energy was 100% and 65% higher, BMC was 61% and 60% higher, and callus tissue volume was 179% and 197% higher than for the control group. Interpretation We found that treatment with PTH during distraction osteogenesis resulted in substantially higher mineralized tissue volume, mineral content, and bending strength. This suggests that treatment with PTH may benefit new bone formation during distraction osteogenesis and could form a basis for clinical application of this therapy in humans. PMID:19995322

2009-01-01

224

The IRE1?-XBP1 Pathway Positively Regulates Parathyroid Hormone (PTH)/PTH-related Peptide Receptor Expression and Is Involved in PTH-induced Osteoclastogenesis*  

PubMed Central

To address the “endoplasmic reticulum stress” triggered by the burden of protein synthesis, the unfolded protein response is induced during osteoblast differentiation. In this study, we show that the transcription of parathyroid hormone (PTH)/PTH-related peptide receptor (PTH1R) is regulated by one of the endoplasmic reticulum-stress mediators, the IRE1?-XBP1 pathway, in osteoblasts. We found that the increase in Pth1r transcription upon BMP2 treatment is significantly suppressed in mouse embryonic fibroblasts lacking IRE1?. As expected, gene silencing of Ire1? and Xbp1 resulted in a decrease in Pth1r transcripts in BMP2-treated embryonic fibroblasts. We identified two potential binding sites for XBP1 in the promoter region of Pth1r and found that XBP1 promotes the transcription of Pth1r by directly binding to those sites. Moreover, we confirmed that the gene silencing of Xbp1 suppresses PTH-induced Rankl expression in primary osteoblasts and thereby abolishes osteoclast formation in an in vitro model of osteoclastogenesis. Thus, the present study reveals potential involvement of the IRE1?-XBP1 pathway in PTH-induced osteoclastogenesis through the regulation of PTH1R expression. PMID:23235147

Tohmonda, Takahide; Yoda, Masaki; Mizuochi, Hiroshi; Morioka, Hideo; Matsumoto, Morio; Urano, Fumihiko; Toyama, Yoshiaki; Horiuchi, Keisuke

2013-01-01

225

A ?-Arrestin–Biased Agonist of the Parathyroid Hormone Receptor (PTH1R) Promotes Bone Formation Independent of G Protein Activation  

PubMed Central

About 40% of the therapeutic agents in use today exert their effects through seven-transmembrane receptors (7TMRs). When activated by ligands, these receptors trigger two pathways that independently transduce signals to the cell: one through heterotrimeric GTP-binding proteins (G proteins) and one through ?-arrestins; so-called biased agonists can selectively activate these distinct pathways. Here, we investigate selective activation of these pathways through the use of a biased agonist for the type 1 parathyroid hormone (PTH)–PTH-related protein receptor (PTH1R), (D-Trp12, Tyr34)-PTH(7–34) (PTH-?arr), which activates ?-arrestin but not classic G protein signaling. In mice, PTH-?arr induces anabolic bone formation, as does the nonselective agonist PTH (1–34), which activates both mechanisms. In ?-arrestin2–null mice, the increase in bone mineral density evoked by PTH(1–34) is attenuated and that stimulated by PTH-?arr is ablated. The ?-arrestin2–dependent pathway contributes primarily to trabecular bone formation and does not stimulate bone resorption. These results show that a biased agonist selective for the ?-arrestin pathway can elicit a response in vivo distinct from that elicited by nonselective agonists. Ligands with these properties may form the basis for improved 7TMR-directed pharmacologic agents with enhanced therapeutic specificity. PMID:20368153

Gesty-Palmer, Diane; Flannery, Pat; Yuan, Ling; Corsino, Leonor; Spurney, Robert; Lefkowitz, Robert J.; Luttrell, Louis M.

2010-01-01

226

LC-MS candidate reference methods for the harmonisation of parathyroid hormone (PTH) measurement: a review of recent developments and future considerations.  

PubMed

The analysis of intact parathyroid hormone (PTH) (PTH1-84) is useful in the diagnosis of hyper- and hypocalcaemia, hyperparathyroidism, and in the prevention of bone mineral disorders in renal patients. The analysis is complicated by the presence of PTH fragments, which may accumulate in renal failure and cross-react in immunoassays, including the most recent third-generation immunoassays. Large variability exists between different commercially available assays. This article reviews the current literature on PTH testing, with emphasis on the use of mass spectrometry-based methods, and considers the important sources of variation which still need to be addressed prior to the development of much needed candidate reference methods for PTH analysis. Recently, mass spectrometric methods have been developed for the quantitation of PTH1-84 using surrogate tryptic peptides, but even these methods are subject to significant interferences due to the presence of newly observed modified PTH species, such as oxidised and phosphorylated PTH variants, which can accumulate in patient samples. Further work, including: 1) the use of high-resolution mass spectrometry; and 2) the analysis of PTH without prior protease digestion, is required before these approaches can be considered as reference methods against which other methods should be harmonised. PMID:24762644

Couchman, Lewis; Taylor, David R; Krastins, Bryan; Lopez, Mary F; Moniz, Cajetan F

2014-09-01

227

Theoretical basis of a beneficial role for vitamin D in viral hepatitis  

PubMed Central

Abnormal bone metabolism and dysfunction of the calcium-parathyroid hormone-vitamin D axis have been reported in patients with viral hepatitis. Some studies suggested a relationship between vitamin D and viral hepatitis. Genetic studies have provided an opportunity to identify the proteins that link vitamin D to the pathology of viral hepatitis (i.e., the major histocompatibility complex class II molecules, the vitamin D receptor, cytochrome P450, the renin-angiotensin system, apolipoprotein E, liver X receptor, toll-like receptor, and the proteins regulated by the Sp1 promoter gene). Vitamin D also exerts its effects on viral hepatitis via non-genomic factors, i.e., matrix metalloproteinase, endothelial vascular growth factor, prostaglandins, cyclooxygenase-2, and oxidative stress. In conclusion, vitamin D could have a beneficial role in viral hepatitis. Calcitriol is best used for viral hepatitis because it is the active form of the vitamin D3 metabolite. PMID:23082050

L??ng, Khanh vinh qu?c; Nguy?n, Lan Thi Hoàng

2012-01-01

228

Parathyroid hormone-related protein and its receptors: nuclear functions and roles in the renal and cardiovascular systems, the placental trophoblasts and the pancreatic islets  

PubMed Central

The cloning of the so-called ‘parathyroid hormone-related protein' (PTHrP) in 1987 was the result of a long quest for the factor which, by mimicking the actions of PTH in bone and kidney, is responsible for the hypercalcemic paraneoplastic syndrome, humoral calcemia of malignancy. PTHrP is distinct from PTH in a number of ways. First, PTHrP is the product of a separate gene. Second, with the exception of a short N-terminal region, the structure of PTHrP is not closely related to that of PTH. Third, in contrast to PTH, PTHrP is a paracrine factor expressed throughout the body. Finally, most of the functions of PTHrP have nothing in common with those of PTH. PTHrP is a poly-hormone which comprises a family of distinct peptide hormones arising from post-translational endoproteolytic cleavage of the initial PTHrP translation products. Mature N-terminal, mid-region and C-terminal secretory forms of PTHrP are thus generated, each of them having their own physiologic functions and probably their own receptors. The type 1 PTHrP receptor, binding both PTH(1-34) and PTHrP(1-36), is the only cloned receptor so far. PTHrP is a PTH-like calciotropic hormone, a myorelaxant, a growth factor and a developmental regulatory molecule. The present review reports recent aspects of PTHrP pharmacology and physiology, including: (a) the identification of new peptides and receptors of the PTH/PTHrP system; (b) the recently discovered nuclear functions of PTHrP and the role of PTHrP as an intracrine regulator of cell growth and cell death; (c) the physiological and developmental actions of PTHrP in the cardiovascular and the renal glomerulo-vascular systems; (d) the role of PTHrP as a regulator of pancreatic beta cell growth and functions, and, (e) the interactions of PTHrP and calcium-sensing receptors for the control of the growth of placental trophoblasts. These new advances have contributed to a better understanding of the pathophysiological role of PTHrP, and will help to identify its therapeutic potential in a number of diseases. PMID:11704631

Clemens, Thomas L; Cormier, Sarah; Eichinger, Anne; Endlich, Karlhans; Fiaschi-Taesch, Nathalie; Fischer, Evelyne; Friedman, Peter A; Karaplis, Andrew C; Massfelder, Thierry; Rossert, Jérôme; Schlüter, Klaus-Dieter; Silve, Caroline; Stewart, Andrew F; Takane, Karen; Helwig, Jean-Jacques

2001-01-01

229

Heterogeneity of pseudohypoparathyroidism type I from the aspect of urinary excretion of calcium and serum levels of parathyroid hormone  

Microsoft Academic Search

Summary  Urinary excretion of calcium (Ca) was measured in 9 patients with pseudohypoparathyroidism (PHP) type I—3 with Albright's\\u000a hereditary osteodystrophy (AHO): AHO(+) and 6 without AHO: AHO(?)—and in 13 with idiopathic hypoparathyroidism (IHP), treated\\u000a with active vitamin D3 (1,25(OH)2D3 or 1?OHD3) to maintain serum Ca levels at 8.4–9.5 mg\\/dl. Fasting urinary excretion of Ca in PHP was significantly lower than that

Kazutoshi Mizunashi; Yohtaro Furukawa; Hyo Euy Sohn; Ryo Miura; Shigeru Yumita; Kaoru Yoshinaga

1990-01-01

230

Regulation of 1,25-dihydroxyvitamin D3 receptor gene expression by 1,25-dihydroxyvitamin D3 in the parathyroid in vivo.  

PubMed Central

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3 dramatically decreases parathyroid hormone (PTH) gene transcription. We have now studied the effect of 1,25(OH)2D3 on the 1,25(OH)2D receptor (VDR) in the parathyroid in vivo. Rats were injected with 1,25(OH)2D3 and the parathyroid-thyroid tissue analyzed for PTHmRNA and VDRmRNA. 1,25(OH)2D3 (50 and 100 pmol ip) decreased PTHmRNA at 6 h with a maximum at 48 h (less than 4% of basal), whereas VDRmRNA was increased only after 6 h with a 1.7-fold increase at 24 h. VDRmRNA levels peaked at 25 pmol 1,25(OH)2D3 with a twofold increase. Serum calcium did not affect VDRmRNA. Parathyroid VDRmRNA ran at 2.2 and 4.4 kb, whereas duodenum VDRmRNA had a single band, all of which increased after 1,25(OH)2D3. Weanling rats on a vitamin D-deficient diet for 3 wk had a more intense 2.2-kb transcript, whereas vitamin D-replete rats had a more intense 4.4-kb band. Dispersed parathyroid-thyroid cells were separated by a flow cytometry (FACS) into a parathyroid cell peak containing PTHmRNA and a second peak with cells positive for thyro-globulin mRNA and calcitonin mRNA. VDRmRNA was concentrated in the parathyroid cell peak. In situ hybridization of parathyroid-thyroid and duodenum for VDRmRNA showed its localization to the parathyroid cells and the duodenal mucosa. Therefore, the VDRmRNA in the parathyroid-thyroid tissue represents predominantly parathyroid cell and not C-cell VDRmRNA which is also a 1,25(OH)2D3 target organ. The increased VDR gene expression in the parathyroid cell would amplify the effect of 1,25(OH)2D3 to decrease PTH gene transcription. Images PMID:2174913

Naveh-Many, T; Marx, R; Keshet, E; Pike, J W; Silver, J

1990-01-01

231

Polybrominated diphenyl ether (PBDE)-induced alterations in vitamin A and thyroid hormone concentrations in the rat during lactation and early postnatal development  

SciTech Connect

In experimental animals fed standard laboratory diets, penta-BDE mixtures can decrease circulating thyroid hormone and liver vitamin A concentrations. A substantial number of pregnant women and their children have marginal vitamin A status, potentially increasing their risk of adverse effects to penta-BDE exposure. The current study investigated the effects of maternal gestational and lactational penta-BDE exposure on thyroid hormone and vitamin A homeostasis in rats of sufficient vitamin A (VAS) or marginal vitamin A (VAM) status and their offspring. Dams were administered daily oral doses of 18 mg/kg DE-71 (a penta-BDE mixture) or a corn oil vehicle from gestation day 6 through lactation day (LD) 18. Thyroid hormone and vitamin A homeostasis were assessed in plasma and tissues of LD 19 dams and postnatal day (PND) 12, 18, and 31 pups. DE-71 exposure induced hepatomegaly in VAS and VAM pups at all timepoints and increased testes weights at PND 31. While liver vitamin A concentrations were low in DE-71 treated dams and pups, plasma retinol concentrations and plasma retinol binding protein levels were only low in VAM animals exposed to DE-71. DE-71 exposure lowered plasma thyroxine concentrations in VAS and VAM dams and pups. Plasma thyroid stimulating hormone concentrations were high in VAM dams exposed to DE-71, suggesting that marginal vitamin A status enhances the susceptibility to thyroid hormone axis disruption by DE-71. These results support the concept that marginal vitamin A status in pregnant women may increase the risk for PBDE-induced disruptions in vitamin A and thyroid hormone homeostasis.

Ellis-Hutchings, Robert G. [Department of Nutrition, University of California-Davis, Davis, CA 95616 (United States); Department of Environmental Toxicology, University of California-Davis, Davis, CA 95616 (United States); Cherr, Gary N. [Department of Nutrition, University of California-Davis, Davis, CA 95616 (United States); Department of Environmental Toxicology, University of California-Davis, Davis, CA 95616 (United States); Bodega Marine Laboratory, University of California-Davis, Bodega Bay, CA 94923 (United States); Hanna, Lynn A. [Department of Nutrition, University of California-Davis, Davis, CA 95616 (United States); Keen, Carl L. [Department of Nutrition, University of California-Davis, Davis, CA 95616 (United States) and Department of Internal Medicine, University of California-Davis, Davis, CA 95616 (United States)]. E-mail: clkeen@ucdavis.edu

2006-09-01

232

Association of Higher Plasma Vitamin D Binding Protein and Lower Free Calcitriol Levels with Tenofovir Disoproxil Fumarate Use and Plasma and Intracellular Tenofovir Pharmacokinetics: Cause of a Functional Vitamin D Deficiency?  

PubMed Central

Tenofovir disoproxil fumarate (TDF) causes bone, endocrine, and renal changes by an unknown mechanism(s). Data are limited on tenofovir pharmacokinetics and these effects. Using baseline data from a multicenter study of HIV-infected youth on stable treatment with regimens containing TDF (n = 118) or lacking TDF (n = 85), we measured cross-sectional associations of TDF use with markers of renal function, vitamin D-calcium-parathyroid hormone balance, phosphate metabolism (tubular reabsorption of phosphate and fibroblast growth factor 23 [FGF23]), and bone turnover. Pharmacokinetic-pharmacodynamic associations with plasma tenofovir and intracellular tenofovir diphosphate concentrations were explored among those receiving TDF. The mean age was 20.9 (standard deviation [SD], 2.0) years; 63% were male; and 52% were African American. Compared to the no-TDF group, the TDF group showed lower mean estimated glomerular filtration rates and tubular reabsorption of phosphate, as well as higher parathyroid hormone and 1,25-dihydroxy vitamin D [1,25-OH(2)D] levels. The highest quintile of plasma tenofovir concentrations was associated with higher vitamin D binding protein, lower free 1,25-OH(2)D, higher 25-OH vitamin D, and higher serum calcium. The highest quintile of intracellular tenofovir diphosphate concentration was associated with lower FGF23. Higher plasma tenofovir concentrations were associated with higher vitamin D binding protein and lower free 1,25-OH(2)D, suggesting a functional vitamin D deficiency explaining TDF-associated increased parathyroid hormone. The finding of lower FGF23 accompanying higher intracellular tenofovir diphosphate suggests that different mechanisms mediate TDF-associated changes in phosphate handling. Separate pharmacokinetic properties may be associated with distinct TDF toxicities: tenofovir with parathyroid hormone and altered calcium balance and tenofovir diphosphate with hypophosphatemia and FGF23 regulation. (The clinical trial registration number for this study is NCT00490412 and is available online at http://clinicaltrials.gov/ct2/show/NCT00490412.) PMID:24002093

Kiser, Jennifer J.; Stephensen, Charles B.; Hazra, Rohan; Flynn, Patricia M.; Wilson, Craig M.; Rutledge, Brandy; Bethel, James; Pan, Cynthia G.; Woodhouse, Leslie R.; Van Loan, Marta D.; Liu, Nancy; Lujan-Zilbermann, Jorge; Baker, Alyne; Kapogiannis, Bill G.; Gordon, Catherine M.

2013-01-01

233

Mineral additives, hormone implants, and vitamin A injections as related to urinary calculi formation in fattening steer calves fed moist sorghum heads  

E-print Network

MINERAL ADDITIVES, HORMONE IMPLANTS, AND VITAMIN A INJECTIONS AS RELATED TO URINARY CALCULI FORMATION XN FATTENING STEER CALVES FED MOIST SORGHUM HEADS A Thesis By WILLIAM S. MCGINNIS Submitted to the Graduate College of the Texas A 8a...M University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE January 1967 Major Subject: Animal Science MINERAL ADDITIVES, HORMONE IMPLANTS, AND VITAMIN A INJECTIONS AS RELATED TO URINARY CALCULI FORMATION IN FATTENING...

McGinnis, William Sams

2012-06-07

234

Role of parathyroid hormone-related protein in the pro-inflammatory and pro-fibrogenic response associated with acute pancreatitis  

PubMed Central

Pancreatitis is a common and potentially lethal necro-inflammatory disease with both acute and chronic manifestations. Current evidence suggests that the accumulated damage incurred during repeated bouts of acute pancreatitis (AP) can lead to chronic disease, which is associated with an increased risk of pancreatic cancer. While parathyroid hormone-related protein (PTHrP) exerts multiple effects in normal physiology and disease states, its function in pancreatitis has not been previously addressed. Here we show that PTHrP levels are transiently elevated in a mouse model of cerulein-induced AP. Treatment with alcohol, a risk factor for both AP and chronic pancreatitis (CP), also increases PTHrP levels. These effects of cerulein and ethanol are evident in isolated primary acinar and stellate cells, as well as in the immortalized acinar and stellate cell lines AR42J and irPSCc3, respectively. Ethanol sensitizes acinar and stellate cells to the PTHrP-modulating effects of cerulein. Treatment of acinar cells with PTHrP (1-36) increases expression of the inflammatory mediators interleukin-6 (IL-6) and intracellular adhesion protein (ICAM-1), suggesting a potential autocrine loop. PTHrP also increases apoptosis in AR42J cells. Stellate cells mediate the fibrogenic response associated with pancreatitis; PTHrP (1-36) increases procollagen I and fibronectin mRNA levels in both primary and immortalized stellate cells. The effects of cerulein and ethanol on levels of IL-6 and procollagen I are suppressed by the PTH1R antagonist, PTHrP (7-34). Together these studies identify PTHrP as a potential mediator of the inflammatory and fibrogenic responses associated with alcoholic pancreatitis. PMID:22280800

Bhatia, Vandanajay; Kim, Sung O.K.; Aronson, Judith F.; Chao, Celia; Hellmich, Mark R.; Falzon, Miriam

2012-01-01

235

Signal transducer and activator of transcription 5a inhibited by pimozide may regulate survival of goat mammary gland epithelial cells by regulating parathyroid hormone-related protein.  

PubMed

The signal transducer and activator of transcription 5a (Stat5a) modulates genes involved in proliferation and survival and plays pivotal roles in regulating the function of the mammary gland during pregnancy, lactation, and involution. However, there is little information about the effects of Stat5a on apoptosis of goat mammary gland epithelial cells (GMECs). In addition, parathyroid hormone-related protein (PTHrP) is a key regulator in cellular calcium transport, mammary gland development and breast tumor biology. This study aimed to explore the interaction of Stat5a and PTHrP in GMEC apoptosis. Quantitative real time PCR (qRT-PCR) suggested that Stat5a was predominantly expressed in the mammary gland, lung, liver and spleen of goats. Treating the GMECs with pimozide, an inhibitor of Stat5a that decreases Stat5a tyrosine phosphorylation, increased PTHrP levels in GMECs in a dose-dependent manner and simultaneously promoted apoptosis of the GMECs. We also demonstrated that PTHrP inhibition induced GMEC apoptosis and restrained cell proliferation. In contrast, PTHrP overexpression protected GMECs from pimozide- and calcium-induced apoptosis, and promoted cell proliferation. Furthermore, pimozide and CaCl2 downregulated the antiapoptotic protein Bcl-2 mRNA expression, respectively, and these effects were protected by PTHrP overexpression. Interestingly, we also found that Stat5a suppressed the expression of matrix metalloproteinase 9 (MMP-9) which can induce goat mammary epithelial cell migration, but PTHrP increased MMP-9 mRNA level. Thus, Stat5a may regulate GMEC survival by regulating the expression of PTHrP. PMID:25194899

Li, Hui; Zheng, Huiling; Sun, Yongsen; Yu, Qian; Li, Lihui

2014-11-10

236

Roles of Parathyroid Hormone (PTH) Receptor and Reactive Oxygen Species in Hyperlipidemia-Induced PTH(1-34) Resistance in Preosteoblasts.  

PubMed Central

Bioactive lipids initiate inflammatory reactions leading to pathogenesis of atherosclerosis. Evidence shows that they also contribute to bone loss by inhibiting parathyroid hormone receptor (PTH1R) expression and differentiation of osteoblasts. We previously demonstrated that bone anabolic effects of PTH(1-34) are blunted in hyperlipidemic mice and that these PTH effects are restored by antioxidants. However, it is not clear which osteoblastic cell developmental stage is targeted by bioactive lipids. To investigate the effects of hyperlipidemia at the cellular level, hyperlipidemic Ldlr?/? mice were bred with Col3.6GFPtpz mice, in which preosteoblasts/osteoblasts carry a topaz fluorescent label, and with Col2.3GFPcyan mice, in which more mature osteoblasts/osteocytes carry a cyan fluorescent label. Histological analyses of trabecular bone surfaces in femoral as well as calvarial bones showed that intermittent PTH(1-34) increased fluorescence intensity in WT-Tpz mice, but not in Tpz-Ldlr?/? mice. In contrast, PTH(1-34) did not alter fluorescence intensity in femoral cortical envelopes of either WT-Cyan or Ldlr?/?-Cyan mice. To test the mechanism of PTH1R downregulation, preosteoblastic MC3T3-E1 cells were treated with bioactive lipids and the antioxidant Trolox. Results showed that inhibitory effects of PTH1R levels by bioactive lipids were rescued by pretreatment with Trolox. The inhibitory effects on expression of PTH1R as well as on PTH-induced osteoblastic genes were mimicked by xanthine/xanthine oxidase, a known generator of reactive oxygen species. These findings suggest an important role of preosteoblasts as the target development stage and downregulation of PTH receptor expression mediated by intracellular oxidant stress as a mechanism in hyperlipidemia-induced PTH resistance. PMID:24038594

Li, Xin; Garcia, Jamie; Lu, Jinxiu; Iriana, Sidney; Kalajzic, Ivo; Rowe, David; Demer, Linda; Tintut, Yin

2013-01-01

237

An Inflection Point of Serum 25-Hydroxyvitamin D for Maximal Suppression of Parathyroid Hormone Is Not Evident from Multi-Site Pooled Data in Children and Adolescents12  

PubMed Central

In adults, maximal suppression of serum parathyroid hormone (PTH) has commonly been used to determine the sufficiency of serum 25-hydroxyvitamin D [25(OH)D]. In children and adolescents, the relationship between serum 25(OH)D and PTH is less clear and most studies reporting a relationship are derived from relatively small samples and homogeneous cohorts. Our objective was to determine the relationship between serum 25(OH)D and PTH in children and adolescents from a large and diverse U.S. cohort and to identify a point of inflection of serum 25(OH)D for maximal suppression of serum PTH. Data from 735 participants, ages 7–18 y, were pooled from 3 study sites located in Indiana, Texas, and Massachusetts. A two-phase linear spline was used to model the relationship between serum 25(OH)D and PTH. The value of serum 25(OH)D for maximal suppression of serum PTH was identified as the inflection point of the spline. Before adjustment for site, the inflection point of serum 25(OH)D for maximal suppression of serum PTH was 92.4 nmol/L (95% CI: 62.2, 130.7). After adjusting for site, the point of inflection was poorly defined and the relationship between serum 25(OH)D and PTH appeared to be linear. The lack of an inflection point of serum 25(OH)D for maximal suppression of PTH brings into question the value of using maximal suppression of serum PTH as a basis for determining optimal serum 25(OH)D for healthy children and adolescents. PMID:20861214

Hill, Kathleen M.; McCabe, George P.; McCabe, Linda D.; Gordon, Catherine M.; Abrams, Steven A.; Weaver, Connie M.

2010-01-01

238

Effect of lead on parathyroid hormone-induced responses in rat osteoblastic osteosarcoma cells (ROS 17/2.8) using 19F-NMR.  

PubMed

Using 19F-NMR and the intracellular divalent cation indicator, 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid, we have recently demonstrated that Pb2+ treatment elevates the intracellular free calcium ion concentration ([Ca2+]i) of rat osteoblastic osteosarcoma cells (ROS 17/2.8) (Proc. Natl. Acad. Sci. USA (1989) 86, 5133-5135). In this study, we have examined the effects of Pb2+ on the basal and parathyroid hormone (PTH)-stimulated levels of [Ca2+]i and cAMP in cultured ROS 17/2.8 cells. PTH treatment (400 ng/ml) stimulated a 150% elevation in [Ca2+]i from a control level of 105 +/- 25 nM to a concentration of 260 +/- 24 nM. Treatment of ROS 17/2.8 cells with Pb2+ (5 microM) alone produced a 50% elevation in the [Ca2+]i to 155 +/- 23 nM. Pb2+ treatment diminished subsequent elevation in [Ca2+]i in response to PTH administration thereby limiting the peak increase in [Ca2+]i to only 25% or 193 +/- 22 nM. In contrast to the dampening effect of Pb2+ on the peak rise in [Ca2+]i produced by PTH, Pb2+ (1 to 25 microM) had no effect on PTH-induced increments in intracellular cAMP levels. Hence, Pb2+ dissociated the PTH stimulation of adenylate cyclase from PTH effects on [Ca2+]i and shifted the regulation of [Ca2+]i beyond the control of PTH modulation. These observations further extend the hypothesis that an early toxic effect of Pb2+ at the cellular level is perturbation of [Ca2+]i homeostasis. PMID:2169314

Schanne, F A; Dowd, T L; Gupta, R K; Rosen, J F

1990-09-01

239

A salt bridge between Arg-20 on parathyroid hormone (PTH) and Asp-137 on the PTH1 receptor is essential for full affinity.  

PubMed

Parathyroid hormone (PTH) acts via the receptor PTH1 and plays an important role in calcium homeostasis. PTH's interaction with the N-terminal domain of PTH1 is mediated in part by Arg-20 on the peptide which forms a number of interactions with the receptor: a charge-charge interaction with Asp-137; hydrogen bonds with the backbone of Asp-29 and Met-32; and hydrophobic interactions with Met-32 and Gln-37. The aim of this work was to establish the importance of the charge-charge interaction through the combined use of modified peptide ligands, site-directed mutations of the receptor, and pharmacological assays. The substitution of Arg-20 with norleucine resulted in a 50-fold reduction in potency at PTH1 and Asp-137-Glu while, in contrast, both Asp-137-Asn and Asp-137-Ala receptors were largely insensitive to this ligand modification. The effect of this removal of the positive charge as position 20 could be partially rescued at PTH1 and Asp-137-Glu, but not Asp-137-Asn and Asp-137-Ala, through a substitution of peptide position 20 with ornithine. The latter two receptors, which have no negative charge at position 137, displayed potency for PTH that was reduced by 40- and 117-fold, respectively. These data demonstrate that a negative charge at residue-137 is important for interacting with ligands containing a positive charge at residue-20, and that the Arg-20 interaction with Asp-137, observed in the crystal structure of the isolated N-terminal domain of PTH1, is likely to be present in the full length receptor where it provides an important affinity- and potency-generating interaction through a salt bridge. PMID:25218037

Weaver, Richard E; Wigglesworth, Mark J; Donnelly, Dan

2014-11-01

240

Parathyroid hormone-related protein overexpression protects goat mammary gland epithelial cells from calcium-sensing receptor activation-induced apoptosis.  

PubMed

Normal mammary gland epithelial cells and breast cancer cells express the calcium-sensing receptor (CaSR), which is the master regulator of systemic calcium metabolism. During lactation, activation of the CaSR in mammary epithelial cells downregulates parathyroid hormone-related protein (PTHrP) levels in milk and in the circulation, and increases calcium transport into milk. However, very little information is available on the role of CaSR in goat mammary gland epithelial cells (GMECs) apoptosis. In this investigation, the full-length cDNA of CaSR from Xinong Saanen dairy goats was cloned, which contains an open-reading frame of 3,258 bp encoding 1,085 amino acids with a predicted molecular weight of 121.0 kDa and an isoelectric point of 5.65. The amino acid sequence is highly homologous with sheep, and the goat CaSR gene is mapped to chromosome 1. Quantitative real-time PCR suggested that CaSR was predominantly expressed in the heart, kidney and mammary gland. Then, we found the stimulation of CaSR with its activator gadolinium chloride (GdCl3) contributed to increase CaSR mRNA levels in GMECs and simultaneously promoted cell apoptosis, and these effects were abrogated partially by NPS2390 which is an inhibitor of CaSR. We also demonstrated that Ca(2+) increased CaSR mRNA levels and induced GMECs apoptosis and restrained cell proliferation. In contrast, PTHrP overexpression protected GMECs from calcium-induced apoptosis, and promoted cell proliferation. In conclusion, these results suggest that PTHrP overexpression protects GMECs from CaSR activation-induced apoptosis. PMID:25266236

Li, Hui; Sun, Yongsen; Zheng, Huiling; Li, Lihui; Yu, Qian; Yao, Xiaotong

2015-01-01

241

Methylation of specific CpG sites in the P2 promoter of parathyroid hormone-related protein determines the invasive potential of breast cancer cell lines.  

PubMed

Parathyroid hormone-related protein (PTHrP) is upregulated in primary breast cancers and a major candidate for osteoclastic bone resorption present at sites of breast cancer to bone metastases. Using a human model of mammary epithelial cell lines differing in tumorigenicity and PTHrP expression, we investigated the role of epigenetic modifications for PTHrP expression. Quantitative analysis of the DNA methylation patterns at a total of 104 CpGs in the promoter region of PTHrP by pyrosequencing showed the absence of methylation in all analyzed cell lines in the large CpG island upstream of exon 1C. In the second intron of promoter 2 (P2) a region was identified containing 4 CpG nucleotides for which differential methylation correlated with the PTHrP expression level. The functional importance of this control mechanism was confirmed by the ability of the demethylating agent 5'-azacytidine to induce PTHrP mRNA and iPTHrP protein expression in previously non-expressing cell lines and increase their production by metastatic NS2T2A1 cells. In particular, transcription from P2 was activated non-tumoral S1T3 cells upon treatment with 5'-azacytidine. Our findings support the hypothesis that the methylation status of specific CpG dinucleotides is the dominant mechanism involved in silencing of PTHrP expression rather than the overall methylation of the CpG island. Methylation of the PTHrP P2 is a potential marker of breast cancer progression and might be used to evaluate the metastatic potential of breast tumors. PMID:21775817

Tost, Jörg; Hamzaoui, Hinda; Busato, Florence; Neyret, Aymeric; Mourah, Samia; Dupont, Jean-Michel; Bouizar, Zhor

2011-08-01

242

Parathyroid hormone enhances fluid shear-induced [Ca2+]i signaling in osteoblastic cells through activation of mechanosensitive and voltage-sensitive Ca2+ channels  

NASA Technical Reports Server (NTRS)

Osteoblasts respond to both fluid shear and parathyroid hormone (PTH) with a rapid increase in intracellular calcium concentration ([Ca2+]i). Because both stimuli modulate the kinetics of the mechanosensitive cation channel (MSCC), we postulated PTH would enhance the [Ca2+]i response to fluid shear by increasing the sensitivity of MSCCs. After a 3-minute preflow at 1 dyne/cm2, MC3T3-E1 cells were subjected to various levels of shear and changes in [Ca2+]i were assessed using Fura-2. Pretreatment with 50 nM bovine PTH(1-34) [bPTH(1-34)] significantly enhanced the shear magnitude-dependent increase in [Ca2+]i. Gadolinium (Gd3+), an MSCC blocker, significantly inhibited the mean peak [Ca2+]i response to shear and shear + bPTH(1-34). Nifedipine (Nif), an L-type voltage-sensitive Ca2+ channel (VSCC) blocker, also significantly reduced the [Ca2+]i response to shear + bPTH(1-34), but not to shear alone, suggesting VSCC activation plays an interactive role in the action of these stimuli together. Activation of either the protein kinase C (PKC) or protein kinase A (PKA) pathways with specific agonists indicated that PKC activation did not alter the Ca2+ response to shear, whereas PKA activation significantly increased the [Ca2+]i response to lower magnitudes of shear. bPTH(1-34), which activates both pathways, induced the greatest [Ca2+]i response at each level of shear, suggesting an interaction of these pathways in this response. These data indicate that PTH significantly enhances the [Ca2+]i response to shear primarily via PKA modulation of the MSCC and VSCC.

Ryder, K. D.; Duncan, R. L.

2001-01-01

243

Postprandial metabolic responses of serum calcium, parathyroid hormone and C-telopeptide of type I collagen to three doses of calcium delivered in milk.  

PubMed

Acute doses of Ca rapidly increase serum Ca and reduce bone resorption concomitant with a reduction in serum parathyroid hormone (PTH) levels. The physiological response to a dose of Ca in milk and to a Ca salt may be different. The present study investigated Ca absorption patterns with increasing levels of fortification in milk, and the response to one dose of a Ca salt. A group of twenty-eight Asian women aged 20-45 years volunteered to attend the laboratory over several weeks. The fasted volunteers were randomised to one of three experimental drinks: 200 ml skimmed milk containing 250, 500 or 1000 mg Ca. A subgroup of seven volunteers also received a calcium gluconate/carbonate salt containing 1000 mg Ca in 200 ml water. Serial blood samples and urine were collected for 5 h from baseline. Different doses of Ca in milk resulted in a graded response in serum corrected Ca, PTH and C-telopeptide of type I collagen (CTx) but not ionised Ca. Serum Ca increased in response to all milk drinks and from 2 to 5 h the blood Ca levels were significantly different for the 250 and 1000 mg doses, as was the integrated response between the loads. The PTH response to the two higher doses was significantly more than following the 250 mg dose. The integrated response for CTx and urinary Ca between all three doses of Ca in milk was significantly different. A dose of Ca salt elicited a more immediate response reaching a plateau faster, and declining faster to baseline. Fortified milk is a safe matrix for delivering larger doses of Ca. PMID:25191614

Kruger, Marlena C; von Hurst, Pamela R; Booth, Christine L; Kuhn-Sherlock, Barbara; Todd, Joanne M; Schollum, Linda M

2014-01-01

244

Parathyroid hormone-related protein in the rat urinary bladder: a smooth muscle relaxant produced locally in response to mechanical stretch.  

PubMed Central

Parathyroid hormone-related protein (PTHrP) gene expression in the pregnant rat uterus has been shown to be dependent on occupancy of the uterus by the fetus. To further test the hypothesis that the synthesis of PTHrP in smooth muscle tissue is regulated by mechanical stretch, we conducted experiments using the rat urinary bladder as a model of an expansible hollow organ. The results indicate that PTHrP mRNA levels do change in response to the stretch of the bladder wall. Under normal conditions PTHrP mRNA levels in the bladder correlated with the urine volume-namely, the extent of bladder distension. When bladders were maintained empty in vivo, PTHrP mRNA levels decreased gradually. Conversely, when bladders were distended by the accumulation of urine, levels of PTHrP mRNA increased dramatically with time. When distension was limited to one-half of the bladder, the increase in PTHrP mRNA was observed only in the distended portion. Histochemical studies performed on distended bladder tissue indicated the presence of PTHrP immunoreactivity in smooth muscle cells. Isolated organ bath studies were used to examine the possible physiological role of PTHrP in smooth muscle tonicity. In vitro responsiveness of bladder muscle strips to exogenous PTHrP was dependent on the in vivo condition of the bladder. In muscle strips obtained from bladders kept empty in vivo, PTHrP-(1-34)-NH2 relaxed carbachol-induced contraction in a dose-dependent manner but failed to relax the contraction in muscle strips from distended bladders that had high endogenous PTHrP expression. These results and the previous findings in the rat uterus suggest a physiological role of PTHrP in bladder smooth muscle function. Images PMID:1376916

Yamamoto, M; Harm, S C; Grasser, W A; Thiede, M A

1992-01-01

245

Mechanistic analysis for time-dependent effects of cinacalcet on serum calcium, phosphorus, and parathyroid hormone levels in 5/6 nephrectomized rats  

PubMed Central

This study investigates the time-dependent effects of cinacalcet on serum calcium, phosphorus, and parathyroid hormone (PTH) levels in 5/6 nephrectomized (NX) rats with experimental chronic renal insufficiency. In this study, 5/6 NX male, Sprague–Dawley rats were treated with vehicle or cinacalcet (10 mg/kg, oral, 1× daily). On Day 0 (before treatment), Day 12 and 13 after treatment (to approximate the clinical practice), and also at 0, 1, 4, 8, 16, and 24 hours after the last dosing, blood was collected for analysis. After 12 or 13 days of cinacalcet treatment, modest changes were observed in serum Ca and phosphorus (Pi), while PTH decreased by >45% to Sham levels (152 ± 15 pg/mL). Detailed mapping found that cinacalcet caused a significant time-dependent decrease in serum Ca following dosing, reaching a lowest point at 8 hours (decrease by 20% to 8.43 ± 0.37 mg/dL), and then returning to normal at 24 hours. Cinacalcet also caused a significant increase in serum Pi levels (by 18%). To investigate the potential mechanism of action, a broad approach was taken by testing cinacalcet in a panel of 77 protein-binding assays. Cinacalcet interacted with several channels, transporters, and neurotransmitter receptors, some of which are involved in brain and heart, and may impact Ca homeostasis. Cinacalcet dose-dependently increased brain natriuretic peptide (BNP) mRNA expression by 48% in cardiomyocytes, but had no significant effects on left ventricular hypertrophy and cardiac function. The results suggest that cinacalcet's hypocalcemic effect may be due to its nonspecific interaction with other receptors in brain and heart. PMID:24303131

Wu-Wong, J Ruth; Nakane, Masaki; Chen, Yung-wu; Mizobuchi, Masahide

2013-01-01

246

Treatment and prevention of chemotherapy-induced alopecia with PTH-CBD, a collagen-targeted parathyroid hormone analog, in a non-depilated mouse model  

PubMed Central

Alopecia is a psychologically devastating complication of chemotherapy for which there is currently no effective therapy. PTH-CBD is a collagen-targeted parathyroid hormone analog that has shown promise as a therapy for alopecia disorders. To compare the efficacy of prophylactic versus therapeutic administration of PTH-CBD in chemotherapy-induced alopecia using a mouse model that mimics the cyclic chemotherapy dosing used clinically. C57BL/6J mice were treated with a single subcutaneous injection of PTH-CBD (320 mcg/kg) or vehicle control before or after hair loss developing from three courses of cyclophosphamide chemotherapy (50–150 mg/kg/week). Mice receiving chemotherapy alone developed hair loss and depigmentation over 6–12 months. Mice pretreated with PTH-CBD did not develop these changes and maintained a normal-appearing coat. Mice treated with PTH-CBD after development of hair loss showed a partial recovery. Observations of hair loss were confirmed quantitatively by gray scale analysis. Histological examination showed that in mice receiving chemotherapy alone, there were small, dystrophic hair follicles mostly in the catagen phase. Mice receiving PTH-CBD before chemotherapy showed a mix of normal-appearing telogen and anagen hair follicles with no evidence of dystrophy. Mice receiving PTH-CBD therapy after chemotherapy showed intermediate histological features. PTH-CBD was effective in both the prevention and the treatment of chemotherapy-induced alopecia in mice, but pretreatment appears to result in a better cosmetic outcome. PTH-CBD shows promise as an agent in the prevention of this complication of chemotherapy and improving the quality of life for cancer patients. PMID:24025564

Katikaneni, Ranjitha; Ponnapakkam, Tulasi; Matsushita, Osamu; Sakon, Joshua; Gensure, Robert

2014-01-01

247

The promotion of osteochondral repair by combined intra-articular injection of parathyroid hormone-related protein and implantation of a bi-layer collagen-silk scaffold.  

PubMed

The repair of osteochondral defects can be enhanced with scaffolds but is often accompanied with undesirable terminal differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Parathyroid hormone-related protein (PTHrP) has been shown to inhibit aberrant differentiation, but administration at inappropriate time points would have adverse effects on chondrogenesis. This study aims to develop an effective tissue engineering strategy by combining PTHrP and collagen-silk scaffold for osteochondral defect repair. The underlying mechanisms of the synergistic effect of combining PTHrP administration with collagen-silk scaffold implantation for rabbit knee joint osteochondral defect repair were investigated. In vitro studies showed that PTHrP treatment significantly reduced Alizarin Red staining and expression of terminal differentiation-related markers. This is achieved in part through blocking activation of the canonical Wnt/?-catenin signaling pathway. For the in vivo repair study, intra-articular injection of PTHrP was carried out at three different time windows (4-6, 7-9 and 10-12 weeks) together with implantation of a bi-layer collagen-silk scaffold. Defects treated with PTHrP at the 4-6 weeks time window exhibited better regeneration (reconstitution of cartilage and subchondral bone) with minimal terminal differentiation (hypertrophy, ossification and matrix degradation), as well as enhanced chondrogenesis (cell shape, Col2 and GAG accumulation) compared with treatment at other time windows. Furthermore, the timing of PTHrP administration also influenced PTHrP receptor expression, thus affecting the treatment outcome. Our results demonstrated that intra-articular injection of PTHrP at 4-6 weeks post-injury together with collagen-silk scaffold implantation is an effective strategy for inhibiting terminal differentiation and enhancing chondrogenesis, thus improving cartilage repair and regeneration in a rabbit model. PMID:23702148

Zhang, Wei; Chen, Jialin; Tao, Jiadong; Hu, Changchang; Chen, Longkun; Zhao, Hongshi; Xu, Guowei; Heng, Boon C; Ouyang, Hong Wei

2013-08-01

248

Thyroid hormone attenuates vascular calcification induced by vitamin d3 plus nicotine in rats.  

PubMed

Thyroid hormones (THs) including thyroxine (T4) and triiodothyronine (T3) play critical roles in bone remodeling. However, the role and mechanism of THs in vascular calcification (VC) have been unclear. To explore the pathophysiological roles of T3 on VC, we investigated the changes in plasma and aortas of THs concentrations and the effect of T3 on rat VC induced by vitamin D3 plus nicotine (VDN). VDN-treated rat showed decreased plasma T3 content, increased vascular calcium deposition, and alkaline phosphatase (ALP) activity. Administration of T3 (0.2 mg/kg body weight IP) for 10 days greatly reduced vascular calcium deposition and ALP activity in calcified rat aortas when compared with controls. Concurrently, the loss of smooth muscle lineage markers ?-actin and SM22a was restored, and the increased bone-associated molecules, such as runt-related transcription factor2 (Runx2), Osterix, and osteopontin (OPN) levels in calcified aorta, were reduced by administration of T3. The suppression of klotho in calcified rat aorta was restored by T3. Methimazole (400 mg/L) blocked the beneficial effect of T3 on VC. These results suggested that T3 can inhibit VC development. PMID:25416842

Zhang, Jing; Chang, Jin-Rui; Duan, Xiao-Hui; Yu, Yan-Rong; Zhang, Bao-Hong

2015-01-01

249

Binding of 1,25-dihydroxyvitamin D3 receptors to the 5'-flanking region of the bovine parathyroid hormone gene.  

PubMed

To further define the binding site for receptors for 1,25(OH)2D3 (VDR) in the bovine PTH gene and to study the interactions of transcription factors with VDR, Southwestern and gel shift assays were used. Data from the former indicated binding of VDR to DNA fragments spanning the regions -451 to -348 bp and -668 to -452 bp. Studies using gel shift assays confirmed binding to the -451 to -348 bp fragment and specificity was shown by using excess concentrations of unlabelled -451 to -348 bp fragment to compete for binding, whereas excess unlabelled -347 to +50 bp did not compete. Binding was also observed with the -668 to -452 bp fragment but excess concentrations of unlabelled -668 to -452 or -451 to -348 bp fragments did not compete for binding to radiolabelled fragments. These data indicate the presence of two binding domains within this region; the upstream element having a lower affinity for VDR than the downstream element. In addition, there was no interaction between VDR and consensus sequences for AP1, AP2, AP3 and SP1. The putative vitamin D3 response element (VDRE) contains two similar hexameric steroid response element-like half-sites placed as AGGTCA-related direct repeats. The upstream repeat is at -461 to -456 bp and the downstream element is at -449 to -444 bp. The presence of these half-sites is consistent with our experimental data in which cleavage with SspI at -452 bp resulted in two DNA fragments which bound VDR. PMID:7964284

Hawa, N S; O'Riordan, J L; Farrow, S M

1994-07-01

250

Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats  

NASA Technical Reports Server (NTRS)

Gonadal insufficiency and reduced mechanical usage are two important risk factors for osteoporosis. The beneficial effects of PTH therapy to reverse the estrogen deficiency-induced bone loss in the laboratory rat are well known, but the influence of mechanical usage in this response has not been established. In this study, the effects of programed administration of PTH on cancellous bone volume and turnover at the proximal tibial metaphysis were determined in hindlimb-unloaded, ovariectomized (OVX), 3-month-old Sprague-Dawley rats. PTH was administered to weight-bearing and hindlimb-unloaded OVX rats with osmotic pumps programed to deliver 20 microg human PTH (approximately 80 microg/kg x day) during a daily 1-h infusion for 7 days. Compared with sham-operated rats, OVX increased longitudinal and radial bone growth, increased indexes of cancellous bone turnover, and resulted in net resorption of cancellous bone. Hindlimb unloading of OVX rats decreased longitudinal and radial bone growth, decreased osteoblast number, increased osteoclast number, and resulted in a further decrease in cancellous bone volume compared with those in weight-bearing OVX rats. Programed administration of PTH had no effect on either radial or longitudinal bone growth in weight-bearing and hindlimb-unloaded OVX rats. PTH treatment had dramatic effects on selected cancellous bone measurements; PTH maintained cancellous bone volume in OVX weight-bearing rats and greatly reduced cancellous bone loss in OVX hindlimb-unloaded rats. In the latter animals, PTH treatment prevented the hindlimb unloading-induced reduction in trabecular thickness, but the hormone was ineffective in preventing either the increase in osteoclast number or the loss of trabecular plates. Importantly, PTH treatment increased the retention of a baseline flurochrome label, osteoblast number, and bone formation in the proximal tibial metaphysis regardless of the level of mechanical usage. These findings demonstrate that programed administration of PTH is effective in increasing osteoblast number and bone formation and has beneficial effects on bone volume in the absence of weight-bearing and gonadal hormones. We conclude that the actions of PTH on cancellous bone are independent of the level of mechanical usage.

Turner, R. T.; Evans, G. L.; Cavolina, J. M.; Halloran, B.; Morey-Holton, E.

1998-01-01

251

Relationships between Vitamin D Status and Cardio-Metabolic Risk Factors in Young European Adults  

Microsoft Academic Search

Background\\/Aims: To explore associations between vitamin D and cardiovascular disease risk factors in young European adults. Methods: This was a cross-sectional analysis of serum 25-hydroxyvitamin D [s25(OH)D], intact parathyroid hormone (iPTH) and biomarkers of cardiovascular disease risk in 195 healthy 20- to 40-year-olds (109 women) with a BMI between 27.5 and 32.5 from Iceland (64°N; n = 82), Ireland (51°N;

S. Muldowney; A. J. Lucey; G. Paschos; J. A. Martinez; N. Bandarra; I. Thorsdottir; K. D. Cashman; M. Kiely

2011-01-01

252

Functioning Oxyphil Parathyroid Adenoma: A Case Report  

PubMed Central

Oxyphil parathyroid adenomas are rare and clinical features of patients with this entity are not well defined. We are presenting a case of primary hyperparathyroidism with marked elevation of parathyroid hormone (PTH) and near normal calcium levels, that underwent parathyroidectomy. Histopathology revealed an oxyphil adenoma which showed positivity for PTH on immunohistochemical staining. Post – operatively, there was a significant decline in both PTH and alkaline phosphatase levels. Benign oxyphil adenomas may mimic parathyroid carcinomas, both in terms of clinical features and tumour size; and they should be considered in the differential diagnosis of patients with primary hyperparathyroidism. PMID:24959490

Metgudmath, Vinita V; Malur, Prakash R; Das, Amal T; Metgudmath, Anjali R

2014-01-01

253

Functioning oxyphil parathyroid adenoma: a case report.  

PubMed

Oxyphil parathyroid adenomas are rare and clinical features of patients with this entity are not well defined. We are presenting a case of primary hyperparathyroidism with marked elevation of parathyroid hormone (PTH) and near normal calcium levels, that underwent parathyroidectomy. Histopathology revealed an oxyphil adenoma which showed positivity for PTH on immunohistochemical staining. Post - operatively, there was a significant decline in both PTH and alkaline phosphatase levels. Benign oxyphil adenomas may mimic parathyroid carcinomas, both in terms of clinical features and tumour size; and they should be considered in the differential diagnosis of patients with primary hyperparathyroidism. PMID:24959490

Metgudmath, Rajendra B; Metgudmath, Vinita V; Malur, Prakash R; Das, Amal T; Metgudmath, Anjali R

2014-04-01

254

Major Haemorrhage during Vitamin K Antagonist Treatment: The Influence of Thyroid Hormone Levels  

PubMed Central

Background Annually, approximately 1-3% of patients treated with vitamin K antagonists (VKA) suffer from major haemorrhage. Since high levels of free thyroxine (fT4) are associated with increased thrombosis risk, the aim was to assess whether low levels of fT4 contribute to major haemorrhage in patients under VKA treatment. Methods The FACTORS (Factors in Oral Anticoagulant Safety) study is a case-control study on patients receiving VKA treatment, including 110 cases with major haemorrhage. Controls were 220 matched participants treated with VKA without major haemorrhage. Odds ratios (OR) and 95% confidence intervals (95% CI) for the association of fT4 levels with major haemorrhage were calculated for different fT4 cutoffs by conditional logistic regression. Results In patients with an fT4 level below 13 pmol/l, the risk of major haemorrhage was 5-fold increased (OR = 5.1; 95% CI: 0.9-28.6) compared with patients with an fT4 level above 13 pmol/l. At a cutoff of 14 pmol/l, the risk was 3-fold increased (OR = 2.9; 95% CI: 1.0-8.5). High levels of fT4 did not affect bleeding risk. No clear effect of thyroid-stimulating hormone and thyroid peroxidase antibodies was seen on the risk of major haemorrhage. Conclusions These results indicate that fT4 levels below 14 pmol/l play a role in the aetiology of major haemorrhage in VKA users. PMID:24847463

Debeij, Jan; Cannegieter, Suzanne C.; van Zaane, Bregje; van Zanten, Anton P.; Rosendaal, Frits R.; Gerdes, Victor E.A.; Reitsma, Pieter H.; Dekkers, Olaf M.

2014-01-01

255

Treatment with N- and C-Terminal Peptides of Parathyroid Hormone-Related Protein Partly Compensate the Skeletal Abnormalities in IGF-I Deficient Mice  

PubMed Central

Insulin-like growth factor-I (IGF-I) deficiency causes growth delay, and IGF-I has been shown to partially mediate bone anabolism by parathyroid hormone (PTH). PTH-related protein (PTHrP) is abundant in bone, and has osteogenic features by poorly defined mechanisms. We here examined the capacity of PTHrP (1–36) and PTHrP (107–111) (osteostatin) to reverse the skeletal alterations associated with IGF-I deficiency. Igf1-null mice and their wild type littermates were treated with each PTHrP peptide (80 µg/Kg/every other day/2 weeks; 2 males and 4 females for each genotype) or saline vehicle (3 males and 3 females for each genotype). We found that treatment with either PTHrP peptide ameliorated trabecular structure in the femur in both genotypes. However, these peptides were ineffective in normalizing the altered cortical structure at this bone site in Igf1-null mice. An aberrant gene expression of factors associated with osteoblast differentiation and function, namely runx2, osteoprotegerin/receptor activator of NF-?B ligand ratio, Wnt3a, cyclin D1, connexin 43, catalase and Gadd45, as well as in osteocyte sclerostin, was found in the long bones of Igf1-null mice. These mice also displayed a lower amount of trabecular osteoblasts and osteoclasts in the tibial metaphysis than those in wild type mice. These alterations in Igf1-null mice were only partially corrected by each PTHrP peptide treatment. The skeletal expression of Igf2, Igf1 receptor and Irs2 was increased in Igf1-null mice, and this compensatory profile was further improved by treatment with each PTHrP peptide related to ERK1/2 and FoxM1 activation. In vitro, PTHrP (1–36) and osteostatin were effective in promoting bone marrow stromal cell mineralization in normal mice but not in IGF-I-deficient mice. Collectively, these findings indicate that PTHrP (1–36) and osteostatin can exert several osteogenic actions even in the absence of IGF-I in the mouse bone. PMID:24503961

Portal-Núñez, Sergio; Murillo-Cuesta, Silvia; Lozano, Daniel; Cediel, Rafael; Esbrit, Pedro

2014-01-01

256

Accelerated bone formation and increased osteoblast number contribute to the abnormal tooth germ development in parathyroid hormone-related protein knockout mice.  

PubMed

Our previous study showed that tooth germs at late embryonic stage [later than embryonic day 17.5 (E17.5)] and neonatal homozygous parathyroid hormone-related protein (PTHrP)-knockout mice are compressed or penetrated by the surrounding alveolar bone tissue. In vivo and in vitro studies have shown that the development of the tooth germ proper is not disturbed, but insufficient alveolar bone resorption, due to the decreased number and hypofunction of osteoclasts, is the main cause of this abnormality. In addition to the insufficient alveolar bone resorption, progressive bone formation toward tooth germs was observed in homozygous mice, suggesting that accelerated bone formation also contributes to this abnormality. To further investigate this, homozygous mice at E14.0 and E15.5, when alveolar bone is forming, were used for histochemical and bone histomorphometric analyses. In contrast to the late embryonic stage, the alveolar bone did not yet compress developing tooth germs in homozygous mice on E14.0, but a larger amount of bone tissue was seen compared to wild-type littermates. Histomorphometric analysis of bone at E14.0 revealed that the osteoblast numbers and surfaces in the mandibles and in the bone collar of femora of homozygous mice were significantly higher than those of wild-type mice. However, unlike our previous study showing the osteoclast surface on E18.5 in homozygous mice to be significantly lower than that of wild-type mice, this study at E14.0 showed no significant difference between the two genotypes. To evaluate the amount of calcification around tooth germs, 3D images of mandibles were reconstructed from the calcein-labeled sections of the wild-type and mutant mice. Labeling was performed at E14.0, and the mice were sacrificed 1 h after the calcein injection to minimize the effect of bone resorption. Comparison of the 3D images revealed that the labeled surface was larger around developing tooth germs in homozygous mouse than in wild-type mouse. On day E15.5, osteoblasts approached the enamel organ of homozygous mice but this was not observed in wild-type mice. In this study, we report a systemic increase in osteoblast number and accelerated bone formation in homozygous PTHrP-knockout mice, both of which contribute to the abnormal tooth development. PMID:15542035

Kitahara, Y; Suda, N; Terashima, T; Baba, O; Mekaapiruk, K; Hammond, V E; Takano, Y; Ohyama, K

2004-11-01

257

Florescent ligand-directed co-localization of the parathyroid hormone 1 receptor with the brush-border scaffold complex of the proximal tubule reveals hormone-dependent changes in ezrin immunoreactivity consistent with inactivation  

PubMed Central

Through binding to parathyroid hormone (PTH), PTH1R interacts with kidney-specific scaffold proteins, including the sodium hydrogen exchanger regulatory factors 1 and 2 (NHERFs), and ezrin. To facilitate in vivo localization, tetramethylrhodamine-labeled PTH (PTH-TMR) was used as a florescent probe. In mice, PTH-TMR localizes to luminal surfaces of tubular S1 segments that overlap PTH1R immunostaining, but does not directly overlap with megalin-specific antibodies. PTH-TMR staining directly overlaps with Npt2a in nascent, endocytic vesicles, marking the location of transporter regulation. PKA substrate antibodies display marked staining increases in segments labeled with PTH-TMR, demonstrating a functional effect. In the presence of secondary hyperparathyroidism, PTH-TMR staining is markedly reduced and shifts to co-localizing with megalin. At 15 minutes post-injection, PTH-TMR-labeled vesicles do not co-localize with either NHERF or ezrin, suggesting PTH1R dissociation from the scaffold complex. At the 5 minute time point, PTH-TMR stains the base of microvilli where it localizes with both NHERF2 and ezrin, and only partially with NHERF1. Strikingly, the bulk of ezrin protein becomes undetectable with the polyclonal, CS3145 antibody, revealing a PTH-induced conformational change in the scaffold. A second ezrin antibody (3C12) is capable of detecting the altered ezrin protein. The CS3145 antibody only binds to the active form of ezrin and fails to recognize the inactive form, while the 3C12 reagent can detect either active or inactive ezrin. Here we show that the PTH1R is part of the ezrin scaffold complex and that acute actions of PTH suggest a rapid inactivation of ezrin in a spatially defined manner. PMID:23036889

Guo, Jun; Song, Lige; Liu, Minlin; Mahon, Matthew J.

2012-01-01

258

Vitamin-D Receptor Genotype Does Not Predict Bone Mineral Density, Bone Turnover, and Growth in Prepubertal Children  

Microsoft Academic Search

We examined whether the polymorphism for BsmI restriction enzyme in the vitamin-D receptor (VDR) gene influenced radial (distal third) and lumbar (L2–L4) bone mineral density (BMD), phospho-calcium metabolism (calcium, phosphate, intact parathyroid hormone, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D), biochemical markers of bone formation (osteocalcin and carboxy-terminal propeptide of type-I procollagen) and bone resorption (carboxy-terminal telopeptide of type-I collagen and urinary

Giampiero I. Baroncelli; Giovanni Federico; Silvano Bertelloni; Cinzia Ceccarelli; Domenico Cupelli; Giuseppe Saggese

1999-01-01

259

Remedial Parathyroid Surgery  

PubMed Central

Objective: To review the outcomes in 130 consecutive remedial explorations for primary hyperparathyroidism. Summary Background Data: Remedial surgery for primary hyperparathyroidism is challenging and requires meticulous preoperative evaluation and imaging to expedite a focused surgical exploration that has traditionally been performed under general anesthesia. This prospective series of 130 consecutive remedial operations for primary hyperparathyroidism selectively used minimally invasive techniques and tested the hypothesis that these techniques could improve outcomes. Methods: Between 1990 and 2005, 1090 patients were evaluated and explored for primary hyperparathyroidism. Of these, 130 remedial explorations were performed in 128 patients who underwent either conventional exploration under general anesthesia (n = 107) or minimally invasive parathyroidectomy (n = 23) employing cervical block anesthesia, directed exploration, and curative confirmation with the rapid intraoperative parathyroid hormone assay. Results: The sensitivity of preoperative imaging were: Sestamibi (79%), ultrasound (74%), MRI (47%), CT (50%), venous localization (93%), and ultrasound guided parathyroid fine needle aspiration (78%). The cure rate in the conventional remedial group (n = 107) was 94% and was associated with a mean length of stay of 1.6 ± 0.2 days. Remedial exploration employing minimally invasive techniques (n = 23) resulted in a cure rate of 96% and a mean length of stay of 0.4 ± 0.1 days. Complications were rare in both remedial groups. These results were almost identical to those achieved in 960 unexplored patients. Conclusions: Remedial parathyroid surgery can be accomplished with acceptable cure and complication rates. Minimally invasive techniques can achieve outcomes that are similar to those obtained in unexplored patients. PMID:16926573

Udelsman, Robert; Donovan, Patricia Irvin

2006-01-01

260

[Parathyroid carcinoma].  

PubMed

Parathyroid carcinoma is a rare condition, comprising less than 1% of the cases of primary hyperparathyroidism (PHP). Nonetheless, due to its aggressiveness, and having prognosis dependent on the precocity of diagnosis and radical therapeutic approach, it is paramount that the clinical suspicion be made before surgery. Clinical presentation is typical of severe PHP, with a parathyroid tumor >1.5 cm, usually palpable. The pathologic features sometimes are difficult to characterize. Our experience with this condition (from 1983 to 2004) includes 7 cases, all symptomatic, hypercalcemic syndrome and bone disease present in most of them. In 6/7 the tumor was palpable, and in all the biochemical profile was compatible with severe PHP. Three patients died of complications of hypercalcemia. Recent findings point to a mutation on the gene HRPT2 as the molecular base for the development of this kind of tumor. The therapeutic approach is surgical and should include ipsilateral thyroidectomy and cervical exploration in order to find possible local metastasis. Post-surgical complications (mainly hypocalcemia) are proportional to the pre-existing metabolic alterations. The long-term prognosis depends upon the precocity of diagnosis, surgical success and control of hypercalcemia. New therapeutic approaches, based on bisphosphonates and calcimimetic drugs, as well as the possibility of genetic diagnosis, tend to ameliorate the prognosis of this severe affection. PMID:16444365

Vieira, José Gilberto H; Ohe, Monique N; Hauache, Omar M; Oliveira, Ulisses Maia de; Delana, Janaina Martins; Gonçalves, André; Lazaretti-Castro, Marise

2005-10-01

261

Developmental expression of neuronal and endocrine markers in the parathyroid glands of the rat  

Microsoft Academic Search

The parathyroid glands of the adult rat harbor a number of neuroendocrine markers, biologically active peptides and ”classical”\\u000a neuromessengers in addition to parathyroid hormone (PTH). Their appearance during parathyroid development is, however, not\\u000a known. In the present study we have examined several neuroendocrine markers and neuromessengers in the parathyroid glands\\u000a of the developing rat [embryonic stage 21(E21), newborn, 1, 2,

L. Luts; F. Sundler

1997-01-01

262

Phosphate metabolism and vitamin D  

PubMed Central

Phosphate plays many essential roles in our body. To accomplish these functions, serum phosphate needs to be maintained in a certain range. Serum phosphate level is regulated by intestinal phosphate absorption, renal phosphate handling and equilibrium of extracellular phosphate with that in bone or intracellular fluid. Several hormones such as parathyroid hormone, 1,25-dihydroxyvitamin D (1,25(OH)2D) and fibroblast growth factor 23 (FGF23) regulate serum phosphate by modulating intestinal phosphate absorption, renal phosphate reabsorption and/or bone metabolism. In addition, dietary phosphate rapidly enhances renal phosphate excretion, although detailed mechanisms of this adaptation remain to be clarified. Physiologically, extracellular concentrations of phosphate and these hormones are maintained by several negative feedback loops. For example, 1,25(OH)2D enhances FGF23 production and FGF23 reduces 1,25(OH)2D level. In addition, phosphate affects 1,25(OH)2D and FGF23 levels. Dysfunction of these negative feedback loops results in several diseases with abnormal phosphate and 1,25(OH)2D levels. Especially, excess actions of FGF23 cause several hypophosphatemic rickets/osteomalacia with relatively low level of 1,25(OH)2D that had been classified as vitamin D-resistant rickets/osteomalacia. In contrast, deficient actions of FGF23 cause hyperphosphatemic familial tumoral calcinosis. However, there still remain several unanswered questions regarding phosphate and vitamin D metabolism. PMID:24605214

Fukumoto, Seiji

2014-01-01

263

Intermittent administration of human parathyroid Hormone(1-34) prevents immobilization-related bone loss by regulating bone marrow capacity for bone cells in ddY mice.  

PubMed

ddY mice, 6 weeks of age, were neurectomized (Nx) in the right hindlimbs and sham-operated (Sham) in the left limbs for evaluation of the effects of intermittent injections of human parathyroid hormone (hPTH) on trabecular bone turnover and bone marrow cell development in unloaded and loaded limbs. Mice were given subcutaneous injections of hPTH(1-34) five times a week at a dose of 0 (vehicle), 4 (low dose), or 40 (high dose) microg/kg of body weight for 2, 4, or 6 weeks. Histomorphometric analyses of the trabecular bone of the proximal tibiae revealed that high-dose hPTH injections preserved the trabecular bone volume of the Nx limbs, which was reduced after neurectomy, at the same level as that of the contralateral Sham limbs. The mineral apposition rate in the Nx limbs was elevated to values above even that of the Sham limbs by high-dose hPTH injections. The bone formation rate reduced by neurectomy was maintained at the Sham level by low- and high-dose hPTH injections. The neurectomy-induced increase in osteoclast number was suppressed by high-dose hPTH injections. In the bone marrow cells, the numbers of nonadherent and adherent cells per tibia obtained from the Nx and Sham limbs did not change. The hPTH injections decreased the numbers of nonadherent cells and increased those of adherent cells in both the Nx and the Sham limbs, but the effects were less marked in the Nx than in the Sham limbs even at high-dose injections. The formation of osteogenic nodules in the marrow cultures obtained from the Nx limbs was decreased after surgery and was maintained at the level of the Sham limbs by high-dose hPTH injections. The number of osteoclast-like multinucleated cells was reduced in the Sham limbs by high-dose hPTH injections. The value was increased at 2 weeks after neurectomy, but it was maintained at the Sham level by high-dose hPTH injections through the experimental period. The numbers of colony forming units-fibroblastic, which were reduced by neurectomy, and those of colony forming units for granulocytes and macrophages were not altered by hPTH injections. These results demonstrate that intermittent high-dose hPTH administration in the Nx limbs as well as in the contralateral Sham limbs has similar anabolic effects, stimulating osteoblast cell lineage and suppressing osteoclast cell lineage. The anabolic effects at 4 microg were reduced, but the effects at 40 microg seemed to be less affected by unloading due to sciatic neurectomy. PMID:10491216

Sakai, A; Sakata, T; Ikeda, S; Uchida, S; Okazaki, R; Norimura, T; Hori, M; Nakamura, T

1999-10-01

264

Vitamin-D nutrition and bone mass in adolescent black girls.  

PubMed Central

OBJECTIVE: To examine the relationship between bone mass and serum levels of 25-hydroxyvitamin D and parathyroid hormone in African-American adolescent girls. STUDY DESIGN: A cross-sectional sample at a suburban research center. METHODS: Twenty-one adolescent black girls 12-14 years of age, were studied during winter with biochemical measurements of serum 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH). Bone mass assessment was done with dual energy x-ray absorbsiometry (DXA) and peripheral quantitative computed tomography of the radius (p-QCT). Anthropometric, physical activity and nutritional data were collected. RESULTS: All participants were vitamin-D deficient (serum 25-OHD level <50 nmol/L), of whom nine (43%) were severely vitamin-D deficient (serum 25-OHD level <20 nmol/L). Mean daily intake of dietary calcium was 540 mg/d and vitamin D was 195 IU/d. There was a positive correlation, although statistically not significant, between serum 25-OHD and various bone mass measurements. Serum PTH was inversely correlated to total body BMD (r = -0.51, p = 0.02) and other bone mineral density at the lumbar spine, total femur and mid-radius. CONCLUSION: Vitamin-D insufficiency is a widely prevalent problem among adolescent African-American girls. Our data implies that enhancing vitamin-D nutrition resulting in lower serum PTH levels could potentially influence their peak bone mass. PMID:17595934

Talwar, Sonia A.; Swedler, Jane; Yeh, James; Pollack, Simcha; Aloia, John F.

2007-01-01

265

Hormones  

MedlinePLUS

Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

266

Vitamin D and skeletal muscle tissue and function.  

PubMed

This review aims to summarize current knowledge on the role of vitamin D in skeletal muscle tissue and function. Vitamin D deficiency can cause a myopathy of varying severity. Clinical studies have indicated that vitamin D status is positively associated with muscle strength and physical performance and inversely associated with risk of falling. Vitamin D supplementation has shown to improve tests of muscle function, reduce falls, and possibly impact on muscle fiber composition and morphology in vitamin D deficient older adults. Molecular mechanisms of vitamin D action on muscle tissue include genomic and non-genomic effects via a receptor present in muscle cells. Genomic effects are initiated by binding of 1,25-dihydroxyvitamin D [1,25(OH)(2)D] to its nuclear receptor, which results in changes in gene transcription of mRNA and subsequent protein synthesis. Non-genomic effects of vitamin D are rapid and mediated through a cell surface receptor. Knockout mouse models of the vitamin D receptor provide insight into understanding the direct effects of vitamin D on muscle tissue. Recently, VDR polymorphisms have been described to affect muscle function. Parathyroid hormone which is strongly linked with vitamin D status also may play a role in muscle function; however, distinguishing its role from that of vitamin D has yet to be fully clarified. Despite the enormous advances in recent decades, further research is needed to fully characterize the exact underlying mechanisms of vitamin D action on muscle tissue and to understand how these cellular changes translate into clinical improvements in physical performance. PMID:18727936

Ceglia, Lisa

2008-12-01

267

Combination Treatment with Progesterone and Vitamin D Hormone May Be More Effective than Monotherapy for Nervous System Injury and Disease  

PubMed Central

More than two decades of pre-clinical research and two recent clinical trials have shown that progesterone (PROG) and its metabolites exert beneficial effects after traumatic brain injury (TBI) through a number of metabolic and physiological pathways that can reduce damage in many different tissues and organ systems. Emerging data on 1,25-dihydroxyvitamin D3 (VDH), itself a steroid hormone, have begun to provide evidence that, like PROG, it too is neuroprotective, although some of its actions may involve different pathways. Both agents have high safety profiles, act on many different injury and pathological mechanisms, and are clinically relevant, easy to administer, and inexpensive. Furthermore, vitamin D deficiency is prevalent in a large segment of the population, especially the elderly and institutionalized, and can significantly affect recovery after CNS injury. The combination of PROG and VDH in pre-clinical and clinical studies is a novel and compelling approach to TBI treatment. PMID:19394357

Cekic, Milos; Sayeed, Iqbal; Stein, Donald G.

2010-01-01

268

Prevalence of vitamin D deficiency among perinatally HIV-infected Thai adolescents receiving antiretroviral therapy.  

PubMed

We assessed the prevalence of vitamin D deficiency among 101 perinatally HIV-infected Thai adolescents receiving antiretroviral therapy. Median age was 14.3 (interquartile range 13.0-15.7) years, and 90% had a HIV RNA<50 copies/mL. The median (interquartile range) 25-hydroxyvitamin D (25-OHD) level was 24.8 (6.9-46.9) ng/mL; 25 (24.7%) had vitamin D deficiency (25-OHD<20 ng/mL) and 47 (46.5%) had insufficiency (25-OHD 20-30 ng/mL). Adolescents with vitamin D deficiency had significantly higher parathyroid hormone levels (54.9 vs. 40.2 pg/mL, P<0.007). No associations between vitamin D deficiency and body mass index, bone mineral density, efavirenz use, HIV RNA, CD4 or self-reported sunlight exposure were observed. PMID:24145954

Chokephaibulkit, Kulkanya; Saksawad, Rachanee; Bunupuradah, Torsak; Rungmaitree, Supattra; Phongsamart, Wanatpreeya; Lapphra, Keswadee; Maleesatharn, Alan; Puthanakit, Thanyawee

2013-11-01

269

Beyond mineral metabolism, is there an interplay between FGF23 and vitamin D in innate immunity?  

PubMed Central

Fibroblast Growth Factor 23 (FGF23) is an ‘endocrine’ FGF acting in the kidney as a phosphaturic hormone and a suppressor of active vitamin D, through an inhibition of the 1? hydroxylase and a stimulation of the 24 hydroxylase. Beyond its well-known effects on the bone/kidney/parathyroid axis and its deregulation during chronic kidney disease (CKD), recent evidence has revealed its direct systemic effects on cardiovascular health. In the meantime, studies have highlighted health implications for vitamin D inside and outside CKD that also extend beyond its classical actions on mineral homeostasis and bone metabolism: vitamin D has indeed been shown to exert pluripotent non-classical effects as a modulator of immune function in monocytes, mainly through the stimulation of the antimicrobial cathelicidin. The aim of this review is to provide new insights on the interplay between FGF23 and vitamin D in innate immunity in the context of CKD. PMID:23117582

Bacchetta, Justine; Salusky, Isidro B; Hewison, Martin

2014-01-01

270

The effects of palm vitamin E on stress hormone levels and gastric lesions in stress-induced rats  

PubMed Central

Introduction This study examines the effects of palm vitamin E (PVE) or ?-tocopherol (?-TF) supplementation on adrenocorticotropin hormone (ACTH), corticosterone and gastric lesions in rats exposed to water-immersion restraint stress (WIRS). Material and methods Sixty male Sprague-Dawley rats (200-250 g) were divided into three groups. Group I: 20 rats as a control group were given a normal diet. Group II: 20 rats received oral supplementation of PVE at 60 mg/kg body weight. Group III: 20 rats received oral supplementation of ?-TF at 60 mg/kg body weight. After the treatment period of 28 days, each group was further subdivided into two groups: 10 rats not exposed to stress, and the other 10 rats subjected to WIRS for 3.5 h. Blood samples were taken to measure the ACTH and corticosterone levels. The rats were then sacrificed and the stomach excised and opened along the greater curvature and examined for lesions. Results Rats exposed to WIRS had lesions in their stomach mucosa. Our findings showed that dietary supplementation of PVE or ?-TF was able to reduce gastric lesions significantly in comparison to the stressed controls. The WIRS increased plasma ACTH and corticosterone significantly. Palm vitamin E and ?-TF treatments reduced these parameters significantly compared to the stressed controls. Conclusions Supplementation with either PVE or ?-TF reduces the formation of gastric lesions, probably by inhibiting the elevation of ACTH and corticosterone levels induced by stress. PMID:22457670

Aziz Ibrahim, Ibrahim Abdel; Kamisah, Yusof; Nafeeza, Mohd Ismail

2012-01-01

271

The Role of Vitamin D in Autoimmune Hepatitis  

PubMed Central

Autoimmune hepatitis is an inflammation of the liver characterized by the presence of peri-portal hepatitis, hypergammaglobulinemia, and the serum autoantibodies. The disease is classified into 2 distinct types according to the nature of auto-antibodies. Disturbances of the calcium-parathyroid hormone-vitamin D axis are frequently associated with chronic liver disease. Patients with AIH have a high prevalence of vitamin D deficiency. Genetic studies have provided the opportunity to determine which proteins link vitamin D to AIH pathology, namely, the major histocompatibility complex class II molecules, vitamin D receptors, toll-like receptors, cytotoxic T lymphocyte antigen-4, cytochrome P450 CYP2D6, regulatory T cells (Tregs) and the forkhead/winged helix transcription factor 3. Vitamin D also exerts its effect on AIH through non-genomic factors, namely, mitogen-activated protein kinase signaling pathways, ??T cells, interferon-gamma nitric oxide synthase, and reactive oxygen stress. In conclusion, vitamin D may have a beneficial role in AIH and improves liver function in concanavalin A-induced mouse AIH. Calcitriol is best used for AIH because it is the active form of a vitamin D3 metabolite and its receptors are present in sinusoidal endothelial cells, Kupffer cells, stellate cells of normal livers, and the biliary cell line. PMID:24171052

Luong, Khanh vinh quoc; Nguyen, Lan Thi Hoang

2013-01-01

272

Single and Combined use of Human Parathyroid Hormone (PTH) (1-34) on Areal Bone Mineral Density (aBMD) in Postmenopausal Women with Osteoporosis: Evidence Based on 9 RCTs  

PubMed Central

Background Human parathyroid hormone (PTH) (1-34) or teriparatide (TPTD) is an anabolic agent for osteoporosis. This recombinant protein stimulates positive bone formation balance and bone remodeling. However, when concomitantly used with antiresorptive (AR) agents, previous studies reported conflicting results in their potential additive and synergistic effects on bone metabolism and bone mineral density (BMD). This study aimed to integrate previous evidence to assess the effect of TPTD monotherapy and the additive effect of TPTD on AR agents in postmenopausal women with osteoporosis. Material/Methods This meta-analysis identified 9 RCTs from databases. To assess the therapeutic effect on osteoporosis, the weighted mean differences (WMDs) were used to pool the percentage change of BMD along with the 95% confidence intervals (CIs). BMD of 3 skeletal sites, including lumbar spine, total hip, and femoral neck were assessed. Results TPTD alone could significantly improve BMD of all 3 skeletal sites compared with placebo, although the effect on the femoral neck was less conclusive. The additive effect of TPTD over hormone replacement therapy (HRT) and denosumab (DEN) agents is evident in all 3 skeletal sites. But TPTD plus Alendronate (ALN) did not demonstrate additive effect in total hip and femoral neck. Conclusions TPTD alone could significantly improve BMD of lumbar spine, total hip, and femoral neck. BMD outcomes of concomitant use of TPTD and AR agents are site-dependent and vary depending on the specific AR agent used and the timing of AR therapy initiation. PMID:25503108

Song, Jiefu; Jing, Zhizhen; Chang, Feng; Li, Lijun; Su, Yunxing

2014-01-01

273

Regulation of Calcitriol Biosynthesis and Activity: Focus on Gestational Vitamin D Deficiency and Adverse Pregnancy Outcomes  

PubMed Central

Vitamin D has garnered a great deal of attention in recent years due to a global prevalence of vitamin D deficiency associated with an increased risk of a variety of human diseases. Specifically, hypovitaminosis D in pregnant women is highly common and has important implications for the mother and lifelong health of the child, since it has been linked to maternal and child infections, small-for-gestational age, preterm delivery, preeclampsia, gestational diabetes, as well as imprinting on the infant for life chronic diseases. Therefore, factors that regulate vitamin D metabolism are of main importance, especially during pregnancy. The hormonal form and most active metabolite of vitamin D is calcitriol. This hormone mediates its biological effects through a specific nuclear receptor, which is found in many tissues including the placenta. Calcitriol synthesis and degradation depend on the expression and activity of CYP27B1 and CYP24A1 cytochromes, respectively, for which regulation is tissue specific. Among the factors that modify these cytochromes expression and/or activity are calcitriol itself, parathyroid hormone, fibroblast growth factor 23, cytokines, calcium and phosphate. This review provides a current overview on the regulation of vitamin D metabolism, focusing on vitamin D deficiency during gestation and its impact on pregnancy outcomes. PMID:25584965

Olmos-Ortiz, Andrea; Avila, Euclides; Durand-Carbajal, Marta; Díaz, Lorenza

2015-01-01

274

Invited commentary: The association of low vitamin D with cardiovascular disease--getting at the "heart and soul" of the relationship.  

PubMed

Low concentrations of 25-hydroxyvitamin D have been consistently associated with cardiovascular disease (CVD) in many observational studies. In an analysis published in this issue of the American Journal of Epidemiology, Welles et al. (Am J Epidemiol. 2014;179(11):1279-1287) used data from 946 participants with stable CVD who were enrolled in the Heart and Soul Study (San Francisco Bay Area, 2000-2012) and found that the association of low 25-hydroxyvitamin D with increased secondary CVD event risk was attenuated after adjustment for parathyroid hormone level, suggesting that parathyroid hormone may mediate this association. They used observational data to gain insight into potential mechanisms underlying the association between vitamin D and CVD risk. Their study focused on secondary CVD events, whereas many previous observational studies have focused on incident CVD events among persons without a history of CVD. In this commentary, we place the study by Welles et al. in context with the existing literature and propose future directions for vitamin D research. We highlight a number of methodological concepts that are important in analyzing vitamin D data, including racial differences in vitamin D concentrations and adjustment for seasonal variation in vitamin D concentrations. We agree that randomized controlled trials should be conducted before making guidelines for screening and treating vitamin D deficiency for the prevention of CVD events. PMID:24699787

Schneider, Andrea L C; Michos, Erin D

2014-06-01

275

The management of acute parathyroid crisis secondary to parathyroid carcinoma: a case report  

PubMed Central

Introduction Hypercalcaemic hyperparathyroid crisis is a rare but life-threatening complication of primary hyperparathyroidism. Parathyroid carcinoma is a rare malignancy with an incidence of 0.5% to 4% of all reported cases of primary hyperparathyroidism. Case presentation We report the case of a 60-year-old Caucasian man with hypercalcaemic hyperparathyroid crisis associated with parathyroid carcinoma. He presented with a classic hypercalcaemic syndrome and his serum calcium and parathyroid hormone levels were at 4.65 mmol/L and 1743 ng/L, respectively. He initially presented with a two-week history of weakness and lethargy and a one-week history of vomiting, polyuria and polydipsia. An emergency left thyroid lobectomy and left lower parathyroidectomy were performed. There was a prompt decrease in his parathyroid hormone level immediately after surgery. Histology revealed that our patient had a 4-cm parathyroid carcinoma. Conclusion In patients with parathyroid carcinoma, the optimal surgical treatment is en bloc resection with ipsilateral thyroid lobectomy and removal of any enlarged or abnormal lymph nodes. Surgery is the only curative treatment. In our patient, prompt surgical intervention proved successful. At six months the patient is well with no evidence of disease recurrence. This case highlights the importance of considering a hyperparathyroid storm in the context of a parathyroid carcinoma. Parathyroid carcinoma is a rare entity and our knowledge is mainly derived from case reports and retrospective studies. This case report increases awareness of this serious and life-threatening complication. This report also illustrates how prompt and appropriate management provides the best outcome for the patient. PMID:20181049

2010-01-01

276

Clinically prescribed sunscreen (sun protection factor 15) does not decrease serum vitamin D concentration sufficiently either to induce changes in parathyroid function or in metabolic markers.  

PubMed

Some studies have suggested that the use of sunscreens to prevent skin cancer may put the population at risk of vitamin D deficiency. We followed 24 sunscreen users and 19 controls over 2 years, including two summers, two winters and a basal period (winter). Vitamin D, parathormone and bone biological markers were evaluated each season. Mean levels of 25-hydroxyvitamin D rose in summer, with the increments being significantly higher for the second year in the control group. Levels decreased in winter in both groups, and were significantly lower in sunscreen users. We did not observe any significant change in parathormone, tartrate resistant phosphatase, total alkaline phosphatase, osteocalcin, urine hydroxyproline or urine calcium. Clinically prescribed sunscreen creams (sun protection factor 15) caused a minor decrease in 25-hydroxyvitamin D levels, which did not induce secondary hyperparathyroidism or an increment in bone biological markers. PMID:9767286

Farrerons, J; Barnadas, M; Rodríguez, J; Renau, A; Yoldi, B; López-Navidad, A; Moragas, J

1998-09-01

277

Vitamin D insufficiency and insulin resistance in obese adolescents.  

PubMed

Obese adolescents represent a particularly vulnerable group for vitamin D deficiency which appears to have negative consequences on insulin resistance and glucose homeostasis. Poor vitamin D status is also associated with future risk of type 2 diabetes and metabolic syndrome in the obese. The biological mechanisms by which vitamin D influences glycemic control in obesity are not well understood, but are thought to involve enhancement of peripheral/hepatic uptake of glucose, attenuation of inflammation and/or regulation of insulin synthesis/secretion by pancreatic ? cells. Related to the latter, recent data suggest that the active form of vitamin, 1,25-dihydroxyvitamin D, does not impact insulin release in healthy pancreatic islets; instead they require an environmental stressor such as inflammation or vitamin D deficiency to see an effect. To date, a number of observational studies exploring the relationship between the vitamin D status of obese adolescents and markers of glucose homeostasis have been published. Most, although not all, show significant associations between circulating 25-hydroxyvitamn D concentrations and insulin sensitivity/resistance indices. In interpreting the collective findings of these reports, significant considerations surface including the effects of pubertal status, vitamin D status, influence of parathyroid hormone status and the presence of nonalcoholic fatty liver disease. The few published clinical trials using vitamin D supplementation to improve insulin resistance and impaired glucose tolerance in obese adolescents have yielded beneficial effects. However, there is a need for more randomized controlled trials. Future investigations should involve larger sample sizes of obese adolescents with documented vitamin D deficiency, and careful selection of the dose, dosing regimen and achievement of target 25-hydroxyvitamn D serum concentrations. These trials should also include clamp-derived measures of in vivo sensitivity and ?-cell function to more fully characterize the effects of vitamin D replenishment on insulin resistance. PMID:25489472

Peterson, Catherine A; Tosh, Aneesh K; Belenchia, Anthony M

2014-12-01

278

Malignancy of parathyroid: An uncommon clinical entity  

PubMed Central

Parathyroid carcinoma is a very rare cause of hyperparathyroidism. The diagnosis is usually established on histopathological grounds of capsular and vascular invasion, but a potential clue to the diagnosis is also offered by the severity of clinical profile, abrupt onset of symptoms, and a high degree of hypercalcemia and raised serum parathyroid hormone (PTH). We report a case of an elderly female with a prolonged history of generalized weakness and bone pain along with bilateral renal calculi, classical bony lesions, and a high serum calcium and PTH level who underwent a right inferior parathyroidectomy considering a parathyroid adenoma as our diagnosis. However, the biopsy report was consistent with a parathyroid carcinoma, and so, she was further subjected to an ipsilateral hemithyroidectomy as a completion procedure. So, we would like to emphasize that its preferable to have a high index of suspicion for parathyroid carcinoma when these clues are present, than to miss the opportunity for surgical cure in the first go by failing to consider it in the differential diagnosis. PMID:23776914

Ali, Kamran; Sarangi, Rathindra; Dhawan, Shashi; Agarwal, Brij B.; Gupta, Manish K.

2013-01-01

279

Aplastic osteodystrophy without aluminum: The role of “suppressed” parathyroid function  

Microsoft Academic Search

Aplastic osteodystrophy without aluminum: The role of “suppressed” parathyroid function. We evaluated 259 dialysis patients using serum parathyroid hormone (PTH, IRMA; normal range 1 to 5.5 pM or 10 to 55 pg\\/ml), the deferoxamine infusion test and iliac crest bone biopsy to determine the various forms of renal osteodystrophy and their risk factors. Although half of the biopsied patients had

Gavril Hercz; Y Pei; C Greenwood; A Manuel; C Saiphoo; W G Goodman; G V Segre; S Fenton; D J Sherrard

1993-01-01

280

The effect of oral vitamin D on serum level of N-terminal pro-B-type natriuretic peptide  

PubMed Central

Background: The risk of cardiovascular disease in dialysis patients is higher than the general population. Vitamin D receptors exist in myocardium inhibit cardiac hypertrophy. N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is a neurohormone secreted by the heart in response to ventricular mass increase. This study aimed to evaluate the effect of oral vitamin D on serum level of pro-B-type natriuretic peptide (pro-BNP) in peritoneal dialysis patients. Materials and Methods: In a randomized clinical trial, 84 peritoneal dialysis patients (49 males and 35 females) were randomly divided into two groups. The intervention group received 50000 units oral vitamin D per week, for 12 weeks if 25-hydroxy-vitamin D level was <10 ng/ml and for 8 weeks if it was between 10 ng/ml and 30 ng/ml. The control group received placebo. Parathyroid hormone, calcium, phosphor, 25-hydroxy-vitamin D, albumin and NT-pro-BNP were evaluated before and after the study. Results: The mean serum level of pro-BNP in patients receiving vitamin D and placebo group before the study was 875 pg/ml and 793 pg/ml, respectively. There was 895.9 pg/ml in the intervention group and 736.7 pg/ml in the control group (P = 0.7). Mean serum level of 25(OH) D in patients receiving oral vitamin D and placebo group before the study was 16.9 ng/ml and 31.9 ng/ml, respectively. There was 28.9 ng/ml in the intervention group and 12.9 ng/ml in the control group (P = 0.001). There were no significant differences regarding other indices (Alb, P, Ca, intact parathyroid hormone) between two groups. Conclusion: Vitamin D did not significantly change the serum level of pro-BNP in peritoneal dialysis patients.

Seirafian, Shiva; Haghdarsaheli, Yalda; Mortazavi, Mojgan; Hosseini, Mohsen; Moeinzadeh, Firouzeh

2014-01-01

281

Repair of Local Bone Erosions and Reversal of Systemic Bone Loss Upon Therapy with Anti-Tumor Necrosis Factor in Combination with Osteoprotegerin or Parathyroid Hormone in Tumor Necrosis Factor-Mediated Arthritis  

PubMed Central

Local bone erosion and systemic bone loss are hallmarks of rheumatoid arthritis and cause progressive disability. Tumor necrosis factor (TNF) is a key mediator of arthritis and acts catabolically on bone by stimulating bone resorption and inhibiting bone formation. We hypothesized that the concerted action of anti-TNF, which reduces inflammation and parathyroid hormone (PTH), which stimulates bone formation, or osteoprotegerin (OPG), which blocks bone resorption and could lead to repair of local bone erosions and reversal of systemic bone loss. To test this, human TNF-transgenic mice with established erosive arthritis and systemic bone loss were treated with PTH, OPG, and anti-TNF, alone or in combination. Local bone erosions almost fully regressed, on combined treatment with anti-TNF and PTH and/or OPG, suggesting repair of inflammatory skeletal lesions. In contrast, OPG and anti-TNF alone led to arrest of bone erosions but did not achieve repair. Treatment with PTH alone had no influence on the progression of bone erosions. Local bone erosions all showed signs of new bone formation such as the presence of osteoblasts, osteoid formation, and mineralization. Furthermore, systemic bone loss was completely reversed on combined treatment and this effect was mediated by osteoblast stimulation and osteoclast blockade. In summary, we conclude that local joint destruction and systemic inflammatory bone loss because of TNF can regress and that repair requires a combined approach by reducing inflammation, blocking bone resorption, or stimulating bone formation. PMID:14742260

Redlich, Kurt; Görtz, Birgit; Hayer, Silvia; Zwerina, Jochen; Doerr, Nicholas; Kostenuik, Paul; Bergmeister, Helga; Kollias, George; Steiner, Günter; Smolen, Josef S.; Schett, Georg

2004-01-01

282

Vitamin D Status and Its Relationship with Metabolic Markers in Persons with Obesity and Type 2 Diabetes in the UAE: A Cross-Sectional Study  

PubMed Central

Aim. To report vitamin D status and its impact on metabolic parameters in people in the United Arab Emirates with obesity and type 2 diabetes (T2D). Methodology. This cross-sectional study included 309 individuals with obesity and T2D who were randomly selected based on study criteria. Serum concentrations of 25-hydroxy vitamin D (s-25(OH)D), calcium, phosphorus, parathyroid hormone, alkaline phosphatase, glycemic profile, and cardiometabolic parameters were assessed in fasting blood samples, and anthropometric measurements were recorded. Results. Vitamin D deficiency (s-25(OH)D < 50?nmol/L) was observed in 83.2% of the participants, with a mean s-25(OH)D of 33.8 ± 20.3?nmol/L. Serum 25(OH)D correlated negatively (P < 0.01) with body mass index, fat mass, waist circumference, parathyroid hormone, alkaline phosphatase, triglycerides, LDL-cholesterol, and apolipoprotein B and positively (P < 0.01) with age and calcium concentration. Waist circumference was the main predictor of s-25(OH)D status. There was no significant association between serum 25(OH)D and glycemic profile. Conclusion. There is an overwhelming prevalence of vitamin D deficiency in our sample of the Emirati population with obesity and T2D. Association of s-25(OH)D with body mass index, waist circumference, fat mass, markers of calcium homeostasis and cardiometabolic parameters suggests a role of vitamin D in the development of cardiometabolic disease-related process. PMID:25371907

Ahmed, Solafa M.; Skaria, Sijomol; Abusnana, Salah

2014-01-01

283

Functional and genetic studies of isolated cells from parathyroid tumors reveal the complex pathogenesis of parathyroid neoplasia  

PubMed Central

Parathyroid adenomas (PAs) causing primary hyperparathyroidism (PHPT) are histologically heterogeneous yet have been historically viewed as largely monotypic entities arising from clonal expansion of a single transformed progenitor. Using flow cytometric analysis of resected adenomatous parathyroid glands, we have isolated and characterized chief cells, oxyphil cells, and tumor-infiltrating lymphocytes. The parathyroid chief and oxyphil cells produce parathyroid hormone (PTH), express the calcium-sensing receptor (CASR), and mobilize intracellular calcium in response to CASR activation. Parathyroid tumor infiltrating lymphocytes are T cells by immunophenotyping. Under normocalcemic conditions, oxyphil cells produce ?50% more PTH than do chief cells, yet display significantly greater PTH suppression and calcium flux response to elevated calcium. In contrast, CASR expression and localization are equivalent in the respective parathyroid cell populations. Analysis of tumor clonality using X-linked inactivation assays in a patient-matched series of intact tumors, preparatively isolated oxyphil and chief cells, and laser-captured microdissected PA specimens demonstrate polyclonality in 5 of 14 cases. These data demonstrate the presence of functionally distinct oxyphil and chief cells within parathyroid primary adenomas and provide evidence that primary PA can arise by both clonal and polyclonal mechanisms. The clonal differences, biochemical activity, and relative abundance of these parathyroid adenoma subpopulations likely reflect distinct mechanisms of disease in PHPT. PMID:24510902

Shi, Yuhong; Hogue, Joyce; Dixit, Darshana; Koh, James; Olson, John A.

2014-01-01

284

Anti-tumor effects of 1,25-dihydroxyvitamin D3 and vitamin D analogs.  

PubMed

The role of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) as a regulator of cell growth and differentiation is well recognized. Currently, 1, 25-(OH)2D3 and vitamin D analogs are being evaluated for their therapeutic potential in the treatment of hyperproliferative disorders like cancer. In the present review, we will discuss several processes that might be involved in 1,25-(OH)2D3- and vitamin D analog-mediated suppression of cancer cell growth. The effects on tumor cell proliferation, differentiation, apoptosis, angiogenesis, metastases, and parathyroid hormone-related peptide secretion will be highlighted. In addition, combination therapy with other tumor effec tive drugs will be addressed. Furtermore, we will focus on the potential drawbacks and the possible side effects of vitamin D compounds in the treatment of cancer. PMID:10828303

van den Bemd, G J; Pols, H A; van Leeuwen, J P

2000-05-01

285

Supplemental vitamin D increases serum cytokines in those with initially low 25-hydroxyvitamin D: A randomized, double blind, placebo-controlled study.  

PubMed

The purpose of this study was to determine if vitamin D status before supplementation influences the cytokine response after supplemental vitamin D. Forty-six reportedly healthy adults (mean(SD); age, 32(7) y; body mass index (BMI), 25.3(4.5) kg/m(2); serum 25-hydroxyvitamin D (25(OH)D), 34.8(12.2) ng/mL) were randomly assigned (double blind) to one of three groups: (1) placebo (n=15), or supplemental vitamin D (cholecalciferol) at (2) 4000 (n=14) or (3) 8000IU (n=17). Supplements were taken daily for 35days. Fasting blood samples were obtained before (Baseline, Bsl) and 35-days after (35-d) supplementation. Serum 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)D), cytokines, and intact parathyroid hormone with calcium were measured in each blood sample. Supplemental vitamin D increased serum 25(OH)D (4000IU, ?29%; 8000IU, ?57%) and 1,25(OH)D (4000IU, ?12%; 8000IU, ?38%) without altering intact parathyroid hormone or calcium. The vitamin D metabolite increases in the supplemental vitamin D groups (n=31) were dependent on initial levels as serum 25(OH)D (r=-0.63, p<0.05) and 1,25(OH)D (r=-0.45, p<0.05) at Bsl correlated with their increases after supplementation. Supplemental vitamin D increased interferon (IFN)-? and interleukin (IL)-10 in subjects that were vitamin D insufficient (serum 25(OH)D<29ng/mL) compared to sufficient (serum 25(OH)D?30ng/mL) at Bsl. We conclude that supplemental vitamin D increase a pro- and anti-inflammatory cytokine in those with initially low serum 25(OH)D. PMID:25461390

Barker, Tyler; Rogers, Victoria E; Levy, Mark; Templeton, Jenna; Goldfine, Howard; Schneider, Erik D; Dixon, Brian M; Henriksen, Vanessa T; Weaver, Lindell K

2015-02-01

286

Prevalence of vitamin D deficiency in peritoneal dialysis patients.  

PubMed

Peritoneal dialysis (PD) patients have a high risk of developing vitamin D deficiency as 25(OH) vitamin D, the precursor of active vitamin D, is lost during dialysis. This cross-sectional study was conducted to investigate the prevalence of vitamin D deficiency among adult Saudi patients on regular PD The data was collected in the summer of 2010 from patients who were on PD for more than six months at the King Khalid University Hospital, Riyadh. We recorded the demographic and clinical parameters for all patients. Blood samples were taken for serum vitamin D level (25 OH), serum parathyroid hormone (PTH) levels and other necessary biochemical parameters. There were 27 patients (11 males and 16 females) with a mean age of 46 (15-78 ± 21) years. Five patients were on continuous ambulatory PD and 22 patients were using automated PD. The average time on PD was 27.5 (6-84 ± 18.5) months. The mean serum vitamin D 25 (OH) level was 16.1 (4.9-41.5 ± 8.23) nmol/L. Sixteen (59.2%) of the patients had levels below 15 nmol/L, while another eight patients (29.6%) had vitamin D levels between 15 and 25 nmol/L, indicating a marked deficiency. The mean serum calcium was 2.2 (1.7-2.6 ± 0.2) mmol/L and the mean serum phosphorous was 1.48 (0.64-2.22 ± 0.37) mmol/L. Fifteen patients (55.5%) had significant hyperparathyroidism (serum PTH levels above 30 pmol/L). Majority of the PD patients in our center had vitamin D deficiency. The possible reasons include chronic renal failure, dietary restrictions, loss of vitamin D and decreased exposure to sunlight. PMID:25193894

Alwakeel, Jamal S; Usama, Saira; Mitwalli, Ahmad H; Alsuwaida, Abdulkareem; Alghonaim, Mohammed

2014-09-01

287

Moderate endurance training has no effect on the parathyroid function of heart transplant patients  

Microsoft Academic Search

The benefit of retraining for heart transplant recipients (HTR) is now well established. The rehabilitation of these patients can be compromised by osteopenia and bone fractures. The resting levels of parathyroid hormone (PTH) and exercise-induced increases are higher in HTR than in healthy controls. To evaluate the effect of a moderate endurance training programme on parathyroid activity, six HTR, an

Anne Charloux; Gabrielle Brandenberger; Eliane Lampert; Florian Chapotot; Claude Gronfier; Bertrand Mettauer; Bernard Geny; Jean Lonsdorfer

1997-01-01

288

Secondary hypertension due to concomitant aldosterone-producing adenoma and parathyroid adenoma.  

PubMed

There is a growing body of evidence supporting a bidirectional relationship between parathyroid hormone (PTH) and aldosterone (Aldo). We report a case of secondary hypertension due to concomitant Aldo-producing adenoma (APA) and parathyroid adenoma (PA) requiring both unilateral adrenalectomy and parathyroidectomy. PMID:24951725

Chau, Katrina; Holmes, Daniel; Melck, Adrienne; Chan-Yan, Clifford

2015-02-01

289

Vitamin D: The “sunshine” vitamin  

PubMed Central

Vitamin D insufficiency affects almost 50% of the population worldwide. An estimated 1 billion people worldwide, across all ethnicities and age groups, have a vitamin D deficiency (VDD). This pandemic of hypovitaminosis D can mainly be attributed to lifestyle (for example, reduced outdoor activities) and environmental (for example, air pollution) factors that reduce exposure to sunlight, which is required for ultraviolet-B (UVB)-induced vitamin D production in the skin. High prevalence of vitamin D insufficiency is a particularly important public health issue because hypovitaminosis D is an independent risk factor for total mortality in the general population. Current studies suggest that we may need more vitamin D than presently recommended to prevent chronic disease. As the number of people with VDD continues to increase, the importance of this hormone in overall health and the prevention of chronic diseases are at the forefront of research. VDD is very common in all age groups. As few foods contain vitamin D, guidelines recommended supplementation at suggested daily intake and tolerable upper limit levels. It is also suggested to measure the serum 25-hydroxyvitamin D level as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D2 or vitamin D3 is recommended for deficient patients. A meta-analysis published in 2007 showed that vitamin D supplementation was associated with significantly reduced mortality. In this review, we will summarize the mechanisms that are presumed to underlie the relationship between vitamin D and understand its biology and clinical implications. PMID:22629085

Nair, Rathish; Maseeh, Arun

2012-01-01

290

Replantation of cryopreserved human parathyroid tissue.  

PubMed

Twenty-five patients with permanent postoperative hypoparathyroidism received cryopreserved parathyroid autografts. Twelve patients had undergone cervical re-operations due to persistent or recurrent hyperparathyroidism and 10 patients had malfunction of a fresh autograft after total parathyroidectomy. Hypoparathyroidism occurred in 2 patients after subtotal parathyroidectomy and in 1 after the resection of a solitary adenoma following previous thyroid resection. The viability of the tissue was examined histologically prior to replantation in 22 patients and the amount of tissue needed for transplantation was determined by the ratio of necrotic cells vs. viable cells in the material. The patients were examined between 6 months and 125 months (median: 40 months) after replantation. Pre-operatively each patient required high doses of calcium and vitamin D metabolites to establish normocalcemia. This medication was reduced postoperatively, with 16 patients requiring no supplemental treatment. Nine patients still needed low doses of calcium and/or vitamin D. At follow-up all patients were free of hypocalcemic symptoms. Our results demonstrate that replantation of autologous cryopreserved parathyroid tissue is safe and effective therapy for permanent postoperative hypoparathyroidism. Thus, we regard it as an essential part of today's parathyroid surgery. PMID:1767542

Wagner, P K; Seesko, H G; Rothmund, M

1991-01-01

291

The effects of programmed administration of human parathyroid hormone fragment (1-34) on bone histomorphometry and serum chemistry in rats  

NASA Technical Reports Server (NTRS)

PTH treatment can result in dramatic increases in cancellous bone volume in normal and osteopenic rats. However, this potentially beneficial response is only observed after pulsatile treatment; continuous infusion of PTH leads to hypercalcemia and bone abnormalities. The purpose of these studies was to determine the optimal duration of the PTH pulses. A preliminary study revealed that human PTH-(1-34) (hPTH) is cleared from circulation within 6 h after sc administration of an anabolic dose of the hormone (80 microg/kg). To establish the effects of gradually extending the duration of exposure to hPTH without increasing the daily dose, we programmed implanted Alzet osmotic pumps to deliver the 80 microg/kg x day dose of the hormone during pulses of 1, 2, and 6 h/day, or 40 microg/kg x day continuously. Discontinuous infusion was accomplished by alternate spacing of external tubing with hPTH solution and sesame oil. After 6 days of treatment, we evaluated serum chemistry and bone histomorphometry. As negative and positive controls, groups of rats received pumps that delivered vehicle only and 80 microg/kg x day hPTH by daily sc injection, respectively. Dynamic and static bone histomorphometry revealed that the daily sc injection and 1 h/day infusion dramatically increased osteoblast number and bone formation in the proximal tibial metaphysis, whereas longer infusion resulted in systemic side-effects, including up to a 10% loss in body weight, hypercalcemia, and histological changes in the proximal tibia resembling abnormalities observed in patients with chronic primary hyperparathyroidism, including peritrabecular marrow fibrosis and focal bone resorption. Infusion for as little as 2 h/day resulted in minor weight loss and changes in bone histology that were intermediate between sc and continuous administration. The results demonstrate that the therapeutic interval for hPTH exposure is brief, but that programmed administration of implanted hormone is a feasible alternative to daily injection as a route for administration of the hormone.

Dobnig, H.; Turner, R. T.

1997-01-01

292

Fat-Soluble Vitamin Status in Self-Neglecting Elderly  

NASA Technical Reports Server (NTRS)

Elder self-neglect is a form of elder mistreatment. The systematic characterization of self-neglecting individuals is the goal of the CREST project. Reported here is the evaluation of fat-soluble vitamin status. Self-neglect (SN) subjects were recruited and consented following referral from Adult Protective Services. Control (CN) subjects were matched for age, gender, race, and socioeconomic status, as possible. We report here on 47 SN subjects (age 77 plus or minus 7, mean plus or minus SD; body weight 76 kg plus or minus 26) and 40 CN subjects (77 y plus or minus 7, 79 kg plus or minus 20). Blood samples were analyzed for indices of fat-soluble vitamin status. Plasma retinol (p less than 0.01) was lower in SN subjects. Plasma tocopherol tended (p less than 0.06) to be lower in SN subjects, while gamma-tocopherol was unchanged. SN subjects tended to have lower serum 25-OH vitamin D (p less than 0.11), and to be vitamin D deficient (26% below 23 mmol/L). Hypercalcemia occurred more often in SN subjects (23% had values above 2.56 mmol/L), as did elevated parathyroid hormone concentrations (p less than 0.05). These data demonstrate that many nutrients are affected in the self-neglecting elderly, and that long-term deficits are evident by the nature of changes in fat soluble vitamins.

Kala, G.; Oliver, S. Mathews; Kelly, P. A.; Pickens, S.; Burnett, J.; Dyer, C. B.; Smith, S. M.

2006-01-01

293

Omega-3 Fatty Acids and Vitamin D in Cardiology  

PubMed Central

Dietary modification and supplementation play an increasingly important role in the conservative treatment of cardiovascular disease. Current interest has focused on n-3 polyunsaturated fatty acids (PUFA) and vitamin D. Clinical trial results on this subject are contradictory in many aspects. Several studies indicate that n-3 PUFA consumption improves vascular and cardiac hemodynamics, triglycerides, and possibly endothelial function, autonomic control, inflammation, thrombosis, and arrhythmia. Experimental studies show effects on membrane structure and associated functions, ion channel properties, genetic regulation, and production of anti-inflammatory mediators. Clinical trials evaluating a possible reduction in cardiovascular disease by n-3 PUFA have shown different results. Supplementation of vitamin D is common regarding prevention and treatment of osteoporosis. But vitamin D also seems to have several effects on the cardiovascular system. Vitamin D deficiency appears to be related to an increase in parathyroid hormone levels and can predispose to essential hypertension and left ventricular hypertrophy, increased insulin resistance, and eventually to atherosclerosis and adverse cardiovascular events. Randomized prospective clinical trials are needed to determine whether vitamin D and omega-3 FA supplementation therapy should be recommended as a routine therapy for primary or secondary prevention of cardiovascular disease. PMID:23346457

Güttler, Norbert; Zheleva, Kirila; Parahuleva, Mariana; Chasan, Ridvan; Bilgin, Mehmet; Neuhof, Christiane; Burgazli, Mehmet; Niemann, Bernd; Erdogan, Ali; Böning, Andreas

2012-01-01

294

Parathyroid Klotho and FGF-receptor 1 expression decline with renal function in hyperparathyroid patients with chronic kidney disease and kidney transplant recipients  

Microsoft Academic Search

Current studies suggest that short-term exposure of parathyroid glands to fibroblast growth factor 23 (FGF23) reduces parathyroid hormone secretion. However, patients with chronic kidney disease (CKD) develop secondary hyperparathyroidism despite high levels of serum FGF23, indicating a parathyroid FGF23 ‘resistance’. Here we analyzed the expression of the FGF23 receptors Klotho and FGF receptor 1 (FGFR1) in 88 hyperplastic parathyroid glands

Tijana Krajisnik; Hannes Olauson; Majd A I Mirza; Per Hellman; Göran Åkerström; Gunnar Westin; Tobias E Larsson; Peyman Björklund

2010-01-01

295

[Method of biopsy and ultrastructural study of the parathyroid gland in patients with primary hyperparathyroidism].  

PubMed

The authors suggest a new method of biopsy of a seemingly normal human parathyroid gland during surgery for parathyroid adenoma. Such a method provides adequate surgical specimen to rule out a likely diffuse hyperplastic disease associated with the parathyroid adenoma, and for the ultrastructural study of the gland, without any risk of postoperative complication. In all patients, ultrastructural examination showed an abnormal cell population and signs of glandular atrophy as a consequence of the high level of serum calcium due to hormonal hyperfunction of the parathyroid adenoma. PMID:9036826

D'Andrea, V; Malinovsky, L; Berni, A; Corbellini, L; Catania, A; Biancari, F; Di Matteo, F M; Lippolis, G; Nisati, L; Santoni, F; De Antoni, E

1996-01-01

296

The administration of intermittent parathyroid hormone affects functional recovery from pertrochanteric fractured neck of femur: a protocol for a prospective mixed method pilot study with randomisation of treatment allocation and blinded assessment (FRACTT)  

PubMed Central

Introduction Pertrochanteric hip fractures occur in an elderly population and cause considerable morbidity and loss of functional ability as the fracture heals. Recently, parathyroid hormone (PTH), which is licensed for the treatment of osteoporosis, has been shown to potentially accelerate bone healing in animal and human studies. If its administration could allow a faster functional recovery after pertrochanteric hip fracture, then a patient's hospital stay may be reduced and rehabilitation could be potentially accelerated. PTH can currently only be administered by subcutaneous injection. The acceptability of this intervention is unknown in this elderly population. The aim of this pilot study is to inform the design of a future powered study comparing the functional recovery after pertrochanteric hip fracture in patients undergoing standard care versus those who undergo administration of subcutaneous injection of PTH. Methods and analysis The study is an open label, prospective, randomised, comparative pilot study with blinded outcomes assessment to establish feasibility of the trial design. Patients will be randomised to receive a 6-week course of PTH or usual treatment. Functional outcomes will be assessed at 6?weeks and 12?weeks. Blinded assessment will be used to minimise the effect of bias of an open label study design. A nested qualitative study will investigate the patient experience of, and expectations following, hip fracture and the patient important aspects of recovery compared with the outcome measures proposed. Results Results will be analysed to establish the potential recruitment, compliance and retention rates using 95% CIs, and trial outcomes quoted with SDs and 95% CIs for the effect size. Ethics and dissemination The study has been approved by the South West 2 Research Ethics committee (reference 10/H0206/34). The findings of this study will be disseminated to the medical community via presentations to orthopaedic, orthogeriatric and osteoporosis societies, and their relevant specialist journals. Trial Registration ISRCTN Register reference number: ISRCTN03362357. Eudract Number: 2010-020081-22 PMID:24477319

Chesser, Tim; Fox, Rebecca; Harding, Karen; Greenwood, Rosemary; Javaid, Kassim; Barnfield, Steven; Halliday, Ruth; Willett, Keith; Lamb, Sallie

2014-01-01

297

Negative Association between Serum Parathyroid Hormone Levels and Urinary Perchlorate, Nitrate, and Thiocyanate Concentrations in U.S. Adults: The National Health and Nutrition Examination Survey 2005–2006  

PubMed Central

Objectives Perchlorate, nitrate, and thiocyanate are well-known inhibitors of the sodium-iodide symporter and may disrupt thyroid function. This exploratory study investigated the association among urinary perchlorate, nitrate, and thiocyanate concentrations and parathyroid hormone (PTH) levels in the general U.S. population. Methods We analyzed data on 4265 adults (aged 20 years and older) from the National Health and Nutrition Examination Survey in 2005 through 2006 to evaluate the relationship among urinary perchlorate, nitrate, and thiocyanate concentration and PTH levels and the presence of hyperparathyroidism cross-sectionally. Results The geometric means and 95% confidence interval (95% CI) concentrations of urinary perchlorate, nitrate, and thiocyanate were 3.38 (3.15–3.62), 40363 (37512–43431), and 1129 (1029–1239) ng/mL, respectively. After adjusting for confounding variables and sample weights, creatinine-corrected urinary perchlorate was negatively associated with serum PTH levels in women (P?=?0.001), and creatinine-corrected urinary nitrate and thiocyanate were negatively associated with serum PTH levels in both sex groups (P?=?0.001 and P<0.001 for men, P?=?0.018 and P<0.001 for women, respectively). Similar results were obtained from sensitivity analyses performed for exposure variables unadjusted for creatinine with urinary creatinine added as a separate covariate. There was a negative relationship between hyperparathyroidism and urinary nitrate and thiocyanate [odds ratio (95% CI)?=?0.77 (0.60–0.98) and 0.69 (0.61–0.79), respectively]. Conclusions A higher urinary concentration of perchlorate, nitrate, and thiocyanate is associated with lower serum PTH levels. Future studies are needed to determine the pathophysiological background of the observation. PMID:25514572

Ko, Wen-Ching; Liu, Chien-Liang; Lee, Jie-Jen; Liu, Tsang-Pai; Yang, Po-Sheng; Hsu, Yi-Chiung; Cheng, Shih-Ping

2014-01-01

298

Experimental induction of parathyroid adenomas in the rat  

SciTech Connect

Neonatal inbred Wistar albino rats were given either 5 or 10 microCi radioiodine (/sup 131/I) within 24 hours of birth. After weaning, animals were placed on diets high, normal, or deficient in vitamin D3 (cholecalciferol) for periods up to 2 years. In animals aged 12 months and older, adenomas were found in 0 of 67 unirradiated controls, in 22 of 67 given 5 microCi /sup 131/I, and in 25 of 67 given to microCi /sup 131/I. The incidence of tumors in irradiated animals was highest (55%) in those on a low-vitamin D diet and lowest (20%) in those on a high-vitamin D diet. Plasma calcium levels were significantly increased by the high-vitamin D diet, but the low-vitamin D diet did not lead to any significant decrease as compared to the calcium levels of the normal vitamin D diet group. Small but significant calcium increases were found in tumor-bearing animals. These findings indicate that parathyroid tumors in the rat can be induced by radiation and that their incidence is strongly influenced by dietary vitamin D content. The possibility that metabolites of vitamin D3 may influence parathyroid growth and tumor formation directly is discussed.

Wynford-Thomas, V.; Wynford-Thomas, D.; Williams, E.D.

1983-01-01

299

Parathyroid cell resistance to fibroblast growth factor 23 in secondary hyperparathyroidism of chronic kidney disease  

Microsoft Academic Search

Although fibroblast growth factor 23 (FGF23) acting through its receptor Klotho-FGFR1c decreases parathyroid hormone expression, this hormone is increased in chronic kidney disease despite an elevated serum FGF23. We measured possible factors that might contribute to the resistance of parathyroid glands to FGF23 in rats with the dietary adenine-induced model of chronic kidney disease. Quantitative immunohistochemical and reverse transcription–PCR analysis

H. Galitzer; I. Z. Ben-Dov; Justin Silver; Tally Naveh-Many

2010-01-01

300

PTH-C1: a rat continuous cell line expressing the parathyroid phenotype.  

PubMed

The lack of a continuous cell line of epithelial parathyroid cells able to produce parathyroid hormone (PTH) has hampered the studies on in vitro evaluation of the mechanisms involved in the control of parathyroid cell function and proliferation. The PT-r cell line was first established from rat parathyroid tissue in 1987, but these cells were known to express the parathyroid hormone-related peptide (Pthrp) gene, but not the Pth gene. In an attempt to subclone the PT-r cell line, a rat parathyroid cell strain was isolated and named PTH-C1. During 3 years, in culture, PTH-C1 cells maintained an epithelioid morphology, displaying a diploid chromosome number, a doubling time around 15 h during the exponential phase of growth, and parathyroid functional features. PTH-C1 cell line produces PTH and expresses the calcium sensing receptor (Casr) gene and other genes known to be involved in parathyroid function. Most importantly, the PTH-C1 cells also exhibit an in vitro secretory response to calcium. Altogether these findings indicate the uniqueness of the PTH-C1 cell line as an in vitro model for cellular and molecular studies on parathyroid physiopathology. PMID:24627164

Fabbri, Sergio; Ciuffi, Simone; Nardone, Valeria; Gomes, Ana Rita; Mavilia, Carmelo; Zonefrati, Roberto; Galli, Gianna; Luzi, Ettore; Tanini, Annalisa; Brandi, Maria Luisa

2014-09-01

301

Influence of Season, Ethnicity, and Chronicity on Vitamin D Deficiency in Traumatic Spinal Cord Injury  

PubMed Central

Background: Inadequate levels of vitamin D increase the risk of osteoporosis, a highly prevalent condition in patients with traumatic spinal cord injury (SCI). Reduced sunlight and dark skin further contribute to low vitamin D levels. Objectives: To compare serum 25-hydroxy vitamin D [vitamin D25(OH)] levels in acute and chronic SCI and to explore seasonal and ethnic differences among patients with acute and chronic SCI. Patients/Methods: Patients (N ?=? 96) aged 19 to 55 years with C3-T10 motor complete SCI participated. Acute SCI was 2 to 6 months after injury, whereas chronic SCI was at least 1 year from injury. Serum vitamin D25(OH), calcium, and parathyroid hormone were drawn during summer or winter months. Vitamin D deficiency (<13 ng/mL), insufficiency (<20 ng/mL), and subtherapeutic (<32 ng/mL) levels were compared for all groups. A 3-way analysis of covariance was adopted to determine significant main effects of season, chronicity, and ethnicity. Interactions between season and chronicity, season and ethnicity, and chronicity and ethnicity were evaluated. Evaluation of a 3-way interaction among season, chronicity, and ethnicity was completed. Results: In summer, 65% of patients with acute SCI and 81% of patients with chronic SCI had subtherapeutic vitamin D levels, whereas in winter, 84% with acute SCI and 96% with chronic SCI had vitamin D25(OH) (<32ng/mL). Lower vitamin D25(OH) levels were observed in African Americans relative to whites. Significant main effects were noted for season (P ?=? 0.017), chronicity (P ?=? 0.003), and ethnicity (P < 0.001). However, interactions between 2 or more factors were not found. Conclusions: Vitamin D insufficiency and deficiency are found in the majority of patients with chronic SCI and in many with acute SCI. Initial screening for serum vitamin D25(OH) levels should be performed early in rehabilitation. Periodic monitoring in the chronic setting is highly recommended. PMID:20737793

Oleson, Christina V; Patel, Payal H; Wuermser, Lisa-Ann

2010-01-01

302

2009 EANM parathyroid guidelines.  

PubMed

The present guidelines were issued by the Parathyroid Task Group of the European Association of Nuclear Medicine. The main focus was imaging of primary hyperparathyroidism. Dual-tracer and single-tracer parathyroid scintigraphy protocols were discussed as well as the various modalities of image acquisition. Primary hyperparathyroidism is an endocrine disorder with high prevalence, typically caused by a solitary parathyroid adenoma, less frequently (about 15%) by multiple parathyroid gland disease (MGD) and rarely (1%) by parathyroid carcinoma. Patients with MGD may have a double adenoma or hyperplasia of three or all four parathyroid glands. Conventional surgery has consisted in routine bilateral neck exploration. The current trend is toward minimally invasive surgery. In this new era, the success of targeted parathyroid surgery depends not only on an experienced surgeon, but also on a sensitive and accurate imaging technique. Recognizing MGD is the major challenge for pre-operative imaging, in order to not direct a patient towards inappropriate minimal surgery. Scintigraphy should also report on thyroid nodules that may cause confusion with a parathyroid adenoma or require concurrent surgical resection. The two main reasons for failed surgery are ectopic glands and undetected MGD. Imaging is mandatory before re-operation, and scintigraphy results should be confirmed with a second imaging technique (usually US for a neck focus, CT or MRI for a mediastinal focus). Hybrid SPECT/CT instruments should be most helpful in this setting. SPECT/CT has a major role for obtaining anatomical details on ectopic foci. However, its use as a routine procedure before target surgery is still investigational. Preliminary data suggest that SPECT/CT has lower sensitivity in the neck area compared to pinhole imaging. Additional radiation to the patient should also be considered. The guidelines also discuss aspects related to radio-guided surgery of hyperparathyroidism and imaging of chronic kidney disease patients with secondary hyperparathyroidism. PMID:19471928

Hindié, Elif; Ugur, Omer; Fuster, David; O'Doherty, Michael; Grassetto, Gaia; Ureña, Pablo; Kettle, Andrew; Gulec, Seza A; Pons, Francesca; Rubello, Domenico

2009-07-01

303

Experience in parathyroid scanning.  

PubMed

In our experience, the low success rate of 75Se parathyroid studies does not justify continuance of the test as a routine diagnostic procedure. The initial results using the 99mTc O4--131I subtraction technique are encouraging but further experience is required in order to ascertain whether this procedure will justify a place as a routine test in the localization of parathyroid adenoma. PMID:1202977

Arkles, L B

1975-11-01

304

Correlation between total vitamin D levels and psychotic psychopathology in patients with schizophrenia: therapeutic implications for add-on vitamin D augmentation  

PubMed Central

Objectives: Vitamin D deficiency is one of the implicated factors in ethio-pathogenesis of schizophrenia. Low serum vitamin D levels have been reported in many schizophrenia studies. However, the question is still not answered: Is there a correlation between disease activity and serum vitamin D levels? This is the first study evaluating the relationship between serum total vitamin D levels and disease activity, by comparing total vitamin D levels in two schizophrenia groups abruptly different in terms of disease activity. Methods: 41 patients with schizophrenia in remission, 40 patients with schizophrenia those in an acute episode and 40 age- and sex -matched controls with no major psychopatology were recruited in this study. Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression – Severety scale (CGI-S) were used to evaluate disease activity. A demographic data form that included entries on age, gender, ethnicity, weight, skin color, daily duration of sun exposure and nutritional assessment were used. Blood samples were taken from all patients and controls. Total vitamin D (D2+D3), calcium, phosphor, parathyroid hormone values were measured. Results: Patients in an acute episode had significantly lower vitamin D levels compared to patients in remission and to healthy controls (in terms of median values respectively, 7.18, 15.03, 15.02, p < 0.001). We observed negative and moderate correlations between vitamin D levels and CGI scores (r = ?0.624, p < 0.001), vitamin D levels and PANNS scores (r = ?0.508, p < 0.001). There were no significant differences between groups in terms of serum P, Ca and PTH levels (p = 0.099, p = 0.943, p = 0.762). We could not detect any significant impact of weekly duration of sun exposure, skin color, ethnicity or nutrition on total vitamin D levels. Conclusions: Even though important factors for vitamin D synthesis were similar, there was severe vitamin D deficiency in patients presenting with an acute episode, significantly different from those in remission. Is vitamin D deficiency the result or the cause of an acute episode? Our results contribute to the idea that vitamin D deficiency and schizophrenia may have interactions with an unknown pathway. Present data points out a possible influence at a genomic level. Future trials may investigate this association with longer follow up. We recommend that, serum vitamin D levels should be measured in patients with schizophrenia especially in long term care. Appropriate further treatment with add-on vitamin D supplements and diets that are rich in vitamin D should be considered. PMID:25489478

Altunsoy, Neslihan; Tikir, Baise; Cingi Külük, Merve; Unal, Kubranur; Goka, Sema; Aydemir, Cigdem; Goka, Erol

2014-01-01

305

Leaf Vitamin C Contents Modulate Plant Defense Transcripts and Regulate Genes That Control Development through Hormone Signaling  

Microsoft Academic Search

Vitamin C deficiency in the Arabidopsis mutant vtc1 causes slow growth and late flowering. This is not attributable to changes in photosynthesis or increased oxidative stress. We have used the vtc1 mutant to provide a molecular signature for vitamin C deficiency in plants. Using statistical analysis, we show that 171 genes are expressed differentially in vtc1 compared with the wild

Gabriela M. Pastori; Guy Kiddle; John Antoniw; Stephanie Bernard; Sonja Veljovic-Jovanovic; Paul J. Verrier; Graham Noctor; Christine H. Foyer

2003-01-01

306

A case of parathyroid carcinoma with a highly aggressive clinical course.  

PubMed

We describe a 59-year-old woman who presented with pathological osteoporosis, cerebral infarction, hypercalcemia, and markedly high parathyroid hormone levels. The diagnosis was primary hyperparathyroidism, and parathyroidectomy was performed. Histopathological examination showed parathyroid adenoma. Surgical exploration for recurrent parathyroid carcinoma was undertaken at 2 and 3 years after the initial neck resection. Pulmonary metastasis was diagnosed at 4 years after the initial surgery.Despite treatment with intravenous bisphosphonates, her calcium and parathyroid hormone (PTH) levels remained elevated, and leg amputation was performed following the development of arteriosclerosis obliterans at 6 years after the initial neck resection. The prognosis for parathyroid carcinoma is often difficult to predict due to recurrence. PMID:25501755

Mori, Hiroko; Okada, Yosuke; Arao, Tadashi; Tanaka, Yoshiya

2014-12-01

307

Natpara Approved for Hormone Disorder Causing Low Blood Calcium  

MedlinePLUS

... Natpara Approved for Hormone Disorder Causing Low Blood Calcium Drug is for people with insufficient parathyroid hormone (* ... Food and Drug Administration to control low blood calcium among people with hypoparathyroidism. Hypoparathyroidism is a rare ...

308

Traumatic Brain Injury and Aging: Is a Combination of Progesterone and Vitamin D Hormone a Simple Solution to a Complex Problem?  

PubMed Central

Summary Although progress is being made in the development of new clinical treatments for traumatic brain injury (TBI), little is known about whether such treatments are effective in older patients, in whom frailty, prior medical conditions, altered metabolism, and changing sensitivity to medications all can affect outcomes following a brain injury. In this review we consider TBI to be a complex, highly variable, and systemic disorder that may require a new pharmacotherapeutic approach, one using combinations or cocktails of drugs to treat the many components of the injury cascade. We review some recent research on the role of vitamin D hormone and vitamin D deficiency in older subjects, and on the interactions of these factors with progesterone, the only treatment for TBI that has shown clinical effectiveness. Progesterone is now in phase III multicenter trial testing in the United States. We also discuss some of the potential mechanisms and pathways through which the combination of hormones may work, singly and in synergy, to enhance survival and recovery after TBI. PMID:20129500

Cekic, Milos; Stein, Donald G.

2010-01-01

309

Health outcomes of vitamin D. Part I. characteristics and classic role.  

PubMed

Vitamin D is a compound responsible for maintaining mineral homeostasis. It protects against calcium and phosphate deficiency through the effects on the intestine, kidney, parathyroid gland and bone. All mechanisms that help maintain mineral homeostasis of the body are regulated by the vitamin D hormonal form - calcitriol. Synthesis of vitamin D starts in the skin as a non-enzymatic process, which begins during exposure to sunlight, when the absorption of ultraviolet B (UVB) radiation results in convertion of 7-dehydrocholesterol, a metabolite of cholesterol that is stored in the skin, to precholecalciferol (previtamin-D?) that is immediately converted into cholecalciferol (vitamin D?). After the skin synthesis cholecalciferol is transported to the liver where it undergoes hydroxylation, what results in formation of calcidiol (25(OH)D?). The second metabolic process takes place in the kidney, where calcidiol undergoes hydroxylation at the C-1 position to the hormonal, the most active metabolite - 1,25-dihydroxyvitamin D (calcitriol). Vitamin D deficiency may result in bone diseases, such as rickets in children and osteomalacia and osteoporosis in adults. Symptoms of osteomalacia affect mainly the skeletal system and are similar to that observed in rickets. It concerns thoracic kyphosis, pelvis deformities and also the varus knee. Osteoporosis is another condition that is related to abnormalities of mineral homeostasis. It is characterized by the progressive loss of bone mass, impaired bone microarchitecture, and consequently increased fragility and susceptibility to fracture. For the last several years other, non-classic actions of vitamin D? have been discussed. It was engendered by the discovery of vitamin D3 receptor (VDR) in the most of body tissues and cells. Hence, there are many hypotheses which suggest the inverse relationship between vitamin D status and various diseases, such as cancer, autoimmune diseases, diabetes mellitus and others. PMID:25247796

Wranicz, Julia; Szostak-W?gierek, Dorota

2014-01-01

310

Parathyroid carcinoma in pregnancy  

PubMed Central

A 24-year-old female patient with parathyroid carcinoma, the rarest endocrine malignancy, had two pregnancies. In the first pregnancy, she had severe nausea and fatigue. Hypercalcemia and hyperparathyroidism were diagnosed in the postpartum period. Hyperemesis gravidarum masked a diagnosis of hypercalcemia. Neck ultrasound and Tc-99m sestamibi found an enlarged lower right parathyroid gland. The gland was surgically removed, and an initial pathology report described atypical adenoma. Shortly afterward, she became pregnant again. During the second pregnancy, her calcium level was frequently controlled but was always in the normal range. Normocalcemia is explained by the specific physiology of pregnancy accompanied by hemodilution, hypoalbuminemia and maternal hypercalciuria (mediated by increased glomerular filtration). During lactation, calcium levels rose, and a new neck ultrasound showed a solitary mass in the area of prior surgery and an enlarged pretracheal lymph node. Fine needle aspiration of the solitary mass and node showed parathyroid carcinoma cells. The tumor mass was resected en bloc with the contiguous tissues and surrounding lymph nodes (pathology report; parathyroid carcinoma with metastases). Over the next five years, four consecutive surgeries were performed to remove malignant parathyroid tissue, lymph nodes and local metastases. Following the surgical procedures, no hypocalcemia was observed. More serious hypercalcemia recurred; the calcium level was difficult to control with a combination of pamidronate, cinacalcet and loop diuretic. No elements of multiple endocrine neoplasia were present. PMID:24868516

Bareti?, Maja; Tomi? Brzac, Hrvojka; Dobreni?, Margareta; Jakov?evi?, Antonia

2014-01-01

311

Effects of glutamine alone or in combination with zinc and vitamin A on growth, intestinal barrier function, stress and satiety-related hormones in Brazilian shantytown children  

PubMed Central

OBJECTIVE: To determine the impact of supplemental zinc, vitamin A, and glutamine alone or in combination on growth, intestinal barrier function, stress and satiety-related hormones among Brazilian shantytown children with low median height-for-age z-scores. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in children aged two months to nine years from the urban shanty compound community of Fortaleza, Brazil. Demographic and anthropometric information was assessed. The random treatment groups available for testing (a total of 120 children) were as follows: (1) glutamine alone, n?=?38; (2) glutamine plus vitamin A plus zinc, n?=?37; and a placebo (zinc plus vitamin A vehicle) plus glycine (isonitrogenous to glutamine) control treatment, n?=?38. Leptin, adiponectin, insulin-like growth factor (IGF-1), and plasma levels of cortisol were measured with immune-enzymatic assays; urinary lactulose/mannitol and serum amino acids were measured with high-performance liquid chromatography. ClinicalTrials.gov: NCT00133406. RESULTS: Glutamine treatment significantly improved weight-for-height z-scores compared to the placebo-glycine control treatment. Either glutamine alone or all nutrients combined prevented disruption of the intestinal barrier function, as measured by the percentage of lactulose urinary excretion and the lactulose:mannitol absorption ratio. Plasma leptin was negatively correlated with plasma glutamine (p?=?0.002) and arginine (p?=?0.001) levels at baseline. After glutamine treatment, leptin was correlated with weight-for-age (WAZ) and weight-for-height z-scores (WHZ) (p?0.002) at a 4-month follow-up. In addition, glutamine and all combined nutrients (glutamine, vitamin A, and zinc) improved the intestinal barrier function in these children. CONCLUSION: Taken together, these findings reveal the benefits of glutamine alone or in combination with other gut-trophic nutrients in growing children via interactions with leptin. PMID:24714829

Lima, Aldo A. M.; Anstead, Gregory M.; Zhang, Qiong; Figueiredo, Ítalo L.; Soares, Alberto M.; Mota, Rosa M. S.; Lima, Noélia L.; Guerrant, Richard L.; Oriá, Reinaldo B.

2014-01-01

312

Parathyroid cyst presenting as acute pancreatitis: report of a case.  

PubMed

We report the first case of hypercalcemia-induced acute pancreatitis caused by a functioning parathyroid cyst in a 67-year-old man. Laboratory investigation revealed increased serum amylase and lipase, increased serum ionized calcium and parathyroid hormone (PTH) levels, and decreased serum phosphate, indicating pancreatitis and primary hyperparathyroidism (PHPT). Abdominal computed tomography (CT) revealed mild swelling of the pancreatic head with peri-pancreatic fat infiltration and fluid collection around the pancreatic tail. Ultrasonography and CT of the neck showed a cystic lesion at the inferior portion of the left thyroid gland, suggesting a parathyroid cyst. There was no evidence of parathyroid adenoma by 99mTc sestamibi scintigraphy. PHPT caused by a functioning parathyroid cyst was suspected. The patient underwent surgical resection of the functioning parathyroid cyst owing to his prolonged hypercalcemia. At 3 weeks after the operation, his serum levels of PTH, total calcium, ionized calcium, inorganic phosphate, amylase, and lipase were normalized. At the follow-up examinations, he has remained asymptomatic. PMID:24400215

Kim, Mi-Young; Chung, Cho-Yun; Kim, Jong-Sun; Myung, Dae-Seong; Cho, Sung-Bum; Park, Chang-Hwan; Kim, Young; Joo, Young-Eun

2013-12-01

313

Apical membrane segregation of phosphatidylinositol-4,5-bisphosphate influences parathyroid hormone 1 receptor compartmental signaling and localization via direct regulation of ezrin in LLC-PK1 cells  

PubMed Central

The parathyroid hormone 1 receptor (PTH1R), a primary regulator of mineral ion homeostasis, is expressed on both the apical and basolateral membranes of kidney proximal tubules and in the LLC-PK1 kidney cell line. In LLC-PK1 cells, apical PTH1R subpopulations are far more effective at signaling via phospholipase (PLC) than basolateral counterparts, revealing the presence of compartmental signaling. Apical PTH1R localization is dependent upon direct interactions with ezrin, an actin-membrane cross-linking scaffold protein. Ezrin undergoes an activation process that is dependent upon phosphorylation and binding to phosphatidylinositol-4,5-bisphosphate (PIP2), a lipid that is selectively concentrated to apical surfaces of polarized epithelia. Consistently, the intracellular probe for PIP2, GFP-PLC?1-PH, localizes to the apical membranes of LLC-PK1 cells, directly overlapping ezrin and PTH1R expression. Activation of the apical PTH1R shifts the GFP-PLC?1-PH probe from the apical membrane to the cytosol and basolateral membranes, reflecting domain-specific activation of PLC and hydrolysis of PIP2. This compartmental signaling is likely due to the polarized localization of PIP2, the substrate for PLC. PIP2 degradation using a membrane-directed phosphatase shifts ezrin localization to the cytosol and induces ezrin de-phosphorylation, processes consistent with inactivation. PIP2 degradation also shifts PTH1R expression from brush border microvilli to basolateral membranes and markedly blunts PTH-elicited activation of the MAPK pathway. Transient expression of ezrin in HEK293 cells shifts PTH1R expression from the plasma membrane to microvilli-like surface projections that also contain PIP2. As a result, ezrin enhances PTH mediated activation of the PLC pathway in this cell model with increasing total receptor surface expression. Collectively, these findings demonstrate that the apical segregation of PIP2 to the apical domains not only promotes the activation of ezrin and the subsequent formation of the PTH1R containing scaffold, but also ensures the presence of ample substrate for propagating the PLC pathway. PMID:21672629

Mahon, Matthew J.

2011-01-01

314

Core binding factor beta (Cbf?) controls the balance of chondrocyte proliferation and differentiation by upregulating Indian hedgehog (Ihh) expression and inhibiting parathyroid hormone-related protein receptor (PPR) expression in postnatal cartilage and bone formation.  

PubMed

Core binding factor beta (Cbf?) is essential for embryonic bone morphogenesis. Yet the mechanisms by which Cbf? regulates chondrocyte proliferation and differentiation as well as postnatal cartilage and bone formation remain unclear. Hence, using paired-related homeobox transcription factor 1-Cre (Prx1-Cre) mice, mesenchymal stem cell-specific Cbf?-deficient (Cbf?(f/f) Prx1-Cre) mice were generated to study the role of Cbf? in postnatal cartilage and bone development. These mutant mice survived to adulthood but exhibited severe sternum and limb malformations. Sternum ossification was largely delayed in the Cbf?(f/f) Prx1-Cre mice and the xiphoid process was noncalcified and enlarged. In newborn and 7-day-old Cbf?(f/f) Prx1-Cre mice, the resting zone was dramatically elongated, the proliferation zone and hypertrophic zone of the growth plates were drastically shortened and disorganized, and trabecular bone formation was reduced. Moreover, in 1-month-old Cbf?(f/f) Prx1-Cre mice, the growth plates were severely deformed and trabecular bone was almost absent. In addition, Cbf? deficiency impaired intramembranous bone formation both in vivo and in vitro. Interestingly, although the expression of Indian hedgehog (Ihh) was largely reduced, the expression of parathyroid hormone-related protein (PTHrP) receptor (PPR) was dramatically increased in the Cbf?(f/f) Prx1-Cre growth plate, indicating that that Cbf? deficiency disrupted the Ihh-PTHrP negative regulatory loop. Chromatin immunoprecipitation (ChIP) analysis and promoter luciferase assay demonstrated that the Runx/Cbf? complex binds putative Runx-binding sites of the Ihh promoter regions, and also the Runx/Cbf? complex directly upregulates Ihh expression at the transcriptional level. Consistently, the expressions of Ihh target genes, including CyclinD1, Ptc, and Pthlh, were downregulated in Cbf?-deficient chondrocytes. Taken together, our study reveals not only that Cbf? is essential for chondrocyte proliferation and differentiation for the growth and maintenance of the skeleton in postnatal mice, but also that it functions in upregulating Ihh expression to promoter chondrocyte proliferation and osteoblast differentiation, and inhibiting PPR expression to enhance chondrocyte differentiation. PMID:24821091

Tian, Fei; Wu, Mengrui; Deng, Lianfu; Zhu, Guochun; Ma, Junqing; Gao, Bo; Wang, Lin; Li, Yi-Ping; Chen, Wei

2014-07-01

315

The Role of Mast Cells in Parathyroid Bone Disease  

PubMed Central

Chronic hyperparathyroidism (HPT) is a common cause of metabolic bone disease. These studies investigated the underlying cellular and molecular mechanisms responsible for the detrimental actions of elevated parathyroid hormone (PTH) on the skeleton. Bone biopsies from hyperparathyroid patients revealed an association between parathyroid bone disease and increased numbers of bone marrow mast cells. We therefore evaluated the role of mast cells in the etiology of parathyroid bone disease in a rat model for chronic HPT. In rats, mature mast cells were preferentially located at sites undergoing bone turnover, and the number of mast cells at the bone–bone marrow interface was greatly increased following treatment with PTH. Time-course studies and studies employing parathyroid hormone–related peptide (PTHrP), as well as inhibitors of platelet-derived growth factor-A (PDGF-A, trapidil), kit (gleevec), and PI3K (wortmannin) signaling revealed that mature mast cell redistribution from bone marrow to bone surfaces precedes and is associated with osteitis fibrosa, a hallmark of parathyroid bone disease. Importantly, mature mast cells were not observed in the bone marrow of mice. Mice, in turn, were resistant to the development of PTH-induced bone marrow fibrosis. These findings suggest that the mast cell may be a novel target for treatment of metabolic bone disease. © 2010 American Society for Bone and Mineral Research. PMID:20200965

Turner, Russell T; Iwaniec, Urszula T; Marley, Kevin; Sibonga, Jean D

2010-01-01

316

Clothing preference affects vitamin D status of young women.  

PubMed

Vitamin D deficiency is associated with several chronic diseases, which include cardiovascular, autoimmune diseases, and cancer. Several factors such as exposure to sunlight, skin color, dietary habits, and cultural factors affect serum vitamin D levels. We hypothesized that serum vitamin D levels in young women are associated with clothing styles and investigated this via a cross-sectional study that included 100 female students at Istanbul Medipol University. Our study used a questionnaire in order to collect demographic information. Serum calcium, 25-hydroxyvitamin D, alkaline phosphatase, and parathyroid hormone levels were determined via standard laboratory tests. We deployed bioelectrical impedance analysis to measure body composition, and we then determined the body mass index (BMI), waist circumference, and total body fat values. The mean age was 20.9 ± 2.1 years. Subjects' data were divided into 2 groups based on their clothing styles: covered (Muslim style clothing) and uncovered. Muslim style clothing, which covers the whole body but leaves the face and hands exposed, was worn by 40.0% of the undergraduate students. The mean BMI (in kilograms per meter squared) of the subjects was 23.0 ± 3.6. The BMI value for the covered students was 24.0 ± 4.0, and that for the uncovered students was 22.3 ± 3.1. Of the subjects, 28.0% had a BMI of at least 25 kg/m(2) (overweight). Serum 25-hydroxyvitamin D (in nanograms per milliliter), parathyroid hormone (in picograms per milliliter), alkaline phosphatase (in units per liter), and calcium levels (in milligrams per deciliter) were 21.1 ± 6.7, 27.5 ± 9.2, 65.9 ± 10.9, and 9.0 ± 0.2 for covered students, respectively, and 29.7 ± 3.1, 24.3 ± 6.1, 62.8 ± 13.2, and 9.0 ± 0.4, respectively, for uncovered students. The prevalence of vitamin D deficiencies was 55.0% for covered and 20.0% for uncovered students. The vitamin D status was found to be statistically significant and had a negative correlation with the duration of Islamic dressing (P < .05, r = -0.334). We concluded that the vitamin D levels of young women are associated with clothing style, and the age at which a female begins wearing Muslim style clothing is related. PMID:25156789

Buyukuslu, Nihal; Esin, Kubra; Hizli, Hilal; Sunal, Nihal; Yigit, Pakize; Garipagaoglu, Muazzez

2014-08-01

317

Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients  

PubMed Central

Prior studies showed conflicting results regarding the association between 25-hydroxyvitamin D (25(OH)D) levels and mineral metabolism in end-stage renal disease. In order to determine whether the bioavailable vitamin D (that fraction not bound to vitamin D binding protein) associates more strongly with measures of mineral metabolism than total levels, we identified 94 patients with previously measured 25(OH)D and 1,25-dihydroxyvitamin D (1,25(OH)2D) from a cohort of incident hemodialysis patients. Vitamin D binding protein was measured from stored serum samples. Bioavailable 25(OH)D and 1,25(OH)2D were determined using previously validated formulae. Associations with demographic factors and measures of mineral metabolism were examined. When compared with whites, black patients had lower levels of total, but not bioavailable, 25(OH)D. Bioavailable, but not total, 25(OH)D and 1,25(OH)2D were each significantly correlated with serum calcium. In univariate and multivariate regression analysis, only bioavailable 25(OH)D was significantly associated with parathyroid hormone levels. Hence, bioavailable vitamin D levels are better correlated with measures of mineral metabolism than total levels in patients on hemodialysis. PMID:22398410

Bhan, Ishir; Powe, Camille E.; Berg, Anders H; Ankers, Elizabeth; Wenger, Julia; Karumanchi, S. Ananth; Thadhani, Ravi

2012-01-01

318

Effect of physical activity on calcium homeostasis and calciotropic hormones: a review.  

PubMed

Physical exercise has frequently been shown to improve bone mass, especially at load-bearing bone sites. It is widely acknowledged that the anabolic effects of exercise on bone tissue are related to the application of mechanical constraints, but part of the osteogenic response may be due to other factors. In particular, various hormonal parameters that are modified by training, such as insulin-like growth factor-1 and sexual hormones, may modulate the bone response. In contrast, little is known about the involvement of calciotropic hormones in the adaptation mechanism of bone tissue. These hormones, which include parathyroid hormone, vitamin D metabolites, and calcitonin, are highly implicated in the regulation of both bone remodeling and calcium homeostasis. In addition to their direct action on bone cell activity, these hormones act on various target tissues such as kidney and intestine. This article describes the acute and long-term effects of exercise on both calcium homeostasis and calciotropic hormones in various populations. It clearly shows that exercise modifies calcium homeostasis and calciotropic hormone levels and that the variations in response are modulated by parameters related to exercise, including duration and intensity, as well as by individual characteristics such as age, sex, and training status. PMID:19760298

Maïmoun, Laurent; Sultan, Charles

2009-10-01

319

Lipothymoadenoma of the parathyroid.  

PubMed

We describe the clinical and morphological features of a most unusual functional mediastinal tumor that combines features of thymolipoma and lipoadenoma of the parathyroid gland. The lesion was unique in that microscopic elements of benign thymic, adipose, and parathyroid tissue were admixed intimately in one partially encapsulated mass. To the best of our knowledge, there has not been a previous description of this tumor. It was excised from a 54-year-old woman with a 10-year history of persistent hyperparathyroidism. The controversial relationship of embryological malformation, hamartoma, and neoplasm is exemplified by this entity. PMID:8442674

van Hoeven, K H; Brennan, M F

1993-03-01

320

Impact of race on hyperparathyroidism, mineral disarrays, administered vitamin D mimetic, and survival in hemodialysis patients.  

PubMed

Blacks have high rates of chronic kidney disease, are overrepresented among the US dialysis patients, have higher parathyroid hormone levels, but greater survival compared to nonblacks. We hypothesized that mineral and bone disorders (MBDs) have a bearing on survival advantages of black hemodialysis patients. In 139,328 thrice-weekly treated hemodialysis patients, including 32% blacks, in a large dialysis organization, where most laboratory values were measured monthly for up to 60 months (July 2001 to June 2006), we examined differences across races in measures of MBDs and survival predictabilities of these markers and administered the active vitamin D medication paricalcitol. Across each age increment, blacks had higher serum calcium and parathyroid hormone (PTH) levels and almost the same serum phosphorus and alkaline phosphatase levels and were more likely to receive injectable active vitamin D in the dialysis clinic, mostly paricalcitol, at higher doses than nonblacks. Racial differences existed in mortality predictabilities of different ranges of serum calcium, phosphorus, and PTH but not alkaline phosphatase. Blacks who received the highest dose of paricalcitol (>10?µg/week) had a demonstrable survival advantage over nonblacks (case-mix-adjusted death hazard ratio?=?0.87, 95% confidence level 0.83-0.91) compared with those who received lower doses (<10?µg/week) or no active vitamin D. Hence, in black hemodialysis patients, hyperparathyroidism and hypercalcemia are more prevalent than in nonblacks, whereas hyperphosphatemia or hyperphosphatasemia are not. Survival advantages of blacks appear restricted to those receiving higher doses of active vitamin D. Examining the effect of MBD modulation on racial survival disparities of hemodialysis patients is warranted. PMID:20614473

Kalantar-Zadeh, Kamyar; Miller, Jessica E; Kovesdy, Csaba P; Mehrotra, Rajnish; Lukowsky, Lilia R; Streja, Elani; Ricks, Joni; Jing, Jennie; Nissenson, Allen R; Greenland, Sander; Norris, Keith C

2010-12-01

321

Vitamin D and Caudal Primary Motor Cortex: A Magnetic Resonance Spectroscopy Study  

PubMed Central

Background Vitamin D is involved in brain physiology and lower-extremity function. We investigated spectroscopy in a cohort of older adults to explore the hypothesis that lower vitamin D status was associated with impaired neuronal function in caudal primary motor cortex (cPMC) measured by proton magnetic resonance spectroscopic imaging. Methods Twenty Caucasian community-dwellers (mean±standard deviation, 74.6±6.2 years; 35.0% female) from the ‘Gait and Brain Study’ were included in this analysis. Ratio of N-acetyl-aspartate to creatine (NAA/Cr), a marker of neuronal function, was calculated in cPMC. Participants were categorized according to mean NAA/Cr. Lower vitamin D status was defined as serum 25-hydroxyvitamin D (25OHD) concentration <75 nmol/L. Age, gender, number of comorbidities, vascular risk, cognition, gait performance, vitamin D supplements, undernourishment, cPMC thickness, white matter hyperintensities grade, serum parathyroid hormone concentration, and season of evaluation were used as potential confounders. Results Compared to participants with high NAA/Cr (n?=?11), those with low NAA/Cr (i.e., reduced neuronal function) had lower serum 25OHD concentration (P?=?0.044) and more frequently lower vitamin D status (P?=?0.038). Lower vitamin D status was cross-sectionally associated with a decrease in NAA/Cr after adjustment for clinical characteristics (??=??0.41, P?=?0.047), neuroimaging measures (??=??0.47, P?=?0.032) and serum measures (??=??0.45, P?=?0.046). Conclusions Lower vitamin D status was associated with reduced neuronal function in cPMC. These novel findings need to be replicated in larger and preferably longitudinal cohorts. They contribute to explain the pathophysiology of gait disorders in older adults with lower vitamin D status, and provide a scientific base for vitamin D replacement trials. PMID:24498072

Annweiler, Cedric; Beauchet, Olivier; Bartha, Robert; Hachinski, Vladimir; Montero-Odasso, Manuel

2014-01-01

322

THE EFFECTS OF DIETARY VITAMIN E AND SELENIUM DEFICIENCIES ON PLASMA THYROID AND THYMIC HORMONE CONCENTRATIONS IN THE CHICKEN  

Technology Transfer Automated Retrieval System (TEKTRAN)

Beginning at hatching, male Cornell K strain single comb white leghorn chickens were fed a basal diet, with or without vitamin E (100 IU/kg) and/or selenium (Se, 0.2 ppm). After 3 weeks of treatment, animals fed either the Se-deficient or basal diet had significantly reduced plasma Se-dependent glut...

323

Controversies on minimally invasive procedures for radio-guided surgery of parathyroid tumours.  

PubMed

The definitive treatment of primary hyperparathyroidism (PHPT) is the surgical approach which traditionally consists of bilateral neck exploration with visualization of at least 4 parathyroid glands and removal of the enlarged ones. However, the most frequent cause of PHPT is a solitary parathyroid adenoma so that a limited neck exploration in order to remove the solitary adenoma alone appears adequate to many surgeons. The recent significant improvements achieved in the pre-operative parathyroid localization techniques, mainly the parathyroid scintigraphy, and the introduction in surgical practice of measurement of quick parathyroid hormone, endoscopic procedures, and intra-operative gamma probes used together specific radiopharmaceuticals allowed to offer the PHPT patient a limited neck exploration as the unilateral neck exploration and the minimally invasive parathyroidectomy. The present article deals with the role of the intra-operative gamma probes used together with specific radio-pharmaceuticals, discussing the principal advantages and disadvantages of each currently used radio-guided approach. PMID:15765028

Rubello, D; Pelizzo, M R; Gross, M D; Fig, L M; Shapiro, B; Rampin, L; Mariani, G

2004-12-01

324

Vascular effects of parathyroid hormone (PTH).  

PubMed

PTH causes dose dependent transient vasodilatation in various vascular beds, specifically renal, coeliac, coronary, but not osseous. It has an acute dose-dependent hypotensive effect in the intact animal which is not mediated by alpha- or beta-adrenergic, cholinergic or histaminergic mechanisms. Aortic medial smooth muscle cells respond to PTH with an increase of cAMP, cGMP and, presumably via protein kinase, with activation of phosphorylase B kinase. The acute vasodilatory effect of PTH is antagonised by indomethacin and diclofenac as well as by ouabain, suggesting that the membrane Na-K pump and prostaglandins are involved in PTH-induced vasodilatation. Parathyroidectomy and a high calcium diet attenuate the rise of arterial pressure in experimental hypertension, pointing to some permissive effect of PTH for development hypertension. This is most likely due to long term effects of PTH on vessel wall calcium content and exchange. This chronic effect of PTH may explain the high prevalence of hypertension in patients with primary hyperparathyroidism. PMID:6758527

Rambausek, M; Ritz, E; Rascher, W; Kreusser, W; Mann, J F; Kreye, V A; Mehls, O

1982-01-01

325

A Spectrum of Clinical Presentations in Seven Japanese Patients with Vitamin D Deficiency  

PubMed Central

Recently, the reemergence of vitamin D deficiency in developed countries has been pointed out. Vitamin D deficiency is diagnosed based on the serum 25-hydroxyvitamin D (25OHD) level. However, its normal range is still controversial, making the diagnosis of vitamin D deficiency difficult. Here, we present seven Japanese patients diagnosed with vitamin D deficiency. Three patients complained of leg bowing, and the other four of tetany. The patients with leg bowing were toddlers. Radiographic surveys demonstrated evidence of rickets. Laboratory findings showed decreased levels of serum inorganic phosphorus and increased levels of alkaline phosphatase (ALP) and intact-parathyroid hormone (iPTH). The serum levels of 25OHD were relatively low, ranging from 13 to 15.2 ng/ml. Of the patients with tetany, three were young infants. Laboratory findings showed decreased levels of serum calcium and increased levels of ALP and iPTH. The serum levels of 25OHD were markedly decreased (below 8 ng/ml). Thus, these results indicate that relatively low levels of 25OHD can cause rickets, a symptom of vitamin D deficiency, and that clinicians should therefore carefully evaluate the levels of 25OHD. PMID:24790316

Kubota, Takuo; Kotani, Tomoo; Miyoshi, Yoko; Santo, Yoko; Hirai, Haruhiko; Namba, Noriyuki; Shima, Masaaki; Shimizu, Kazuo; Nakajima, Shigeo; Ozono, Keiichi

2006-01-01

326

Ectopic parathyroid adenoma localized with MIBI scintigraphy and excised with guide of macroaggregated human serum albumin injection.  

PubMed

Primary hyperparathyroidism is caused by an excessive amount of parathyroid hormone secreted by one or more enlarged parathyroid glands. Most commonly primary hyperparathyroidism is caused by a parathyroid adenoma. Ectopic parathyroid adenomas are rare, but they can complicate the surgical treatment and have an increased morbidity and poorer success rate. Thus, preoperative imaging is particularly valuable in this group of patients with hyperparathyroidism. Preoperative imaging has opened up a new era of minimally invasive parathyroid surgery procedures. The radioguided occult lesion localization technique has become the preferred approach to preoperative localization of nonpalpable breast lesions in several breast units. In this report, we investigated the usefulness of the radio-guided occult lesion localization technique in the identification of ectopic parathyroid adenomas. We describe the case of a 66-year-old woman who was diagnosed to be hypercalcemic. Tc-99m methoxy-isobutyl-isonitrile scintigraphy identified an ectopic parathyroid adenoma. The patient's cervical region was scanned with the probe to localize an area of maximal radiotracer uptake and the hot area was identified by a gamma probe. Careful dissection was then carried out and an enlarged ectopic parathyroid gland was removed. In conclusion, the preoperative imaging of an ectopic parathyroid adenoma and the excision of this tissue with radioguided occult lesion localization technique can open up a new era of minimally invasive parathyroid surgery. PMID:20173443

Aliyev, Anar; Kabasakal, Levent; Simsek, Osman; Paksoy, Melih; Halac, Metin; Uslu, Ilhami

2010-03-01

327

Consequences of a deficit in vitamin b6 biosynthesis de novo for hormone homeostasis and root development in Arabidopsis.  

PubMed

Vitamin B6 (pyridoxal 5'-phosphate) is an essential cofactor of many metabolic enzymes. Plants biosynthesize the vitamin de novo employing two enzymes, pyridoxine synthase1 (PDX1) and PDX2. In Arabidopsis (Arabidopsis thaliana), there are two catalytically active paralogs of PDX1 (PDX1.1 and PDX1.3) producing the vitamin at comparable rates. Since single mutants are viable but the pdx1.1 pdx1.3 double mutant is lethal, the corresponding enzymes seem redundant. However, the single mutants exhibit substantial phenotypic differences, particularly at the level of root development, with pdx1.3 being more impaired than pdx1.1. Here, we investigate the differential regulation of PDX1.1 and PDX1.3 by identifying factors involved in their disparate phenotypes. Swapped-promoter experiments clarify the presence of distinct regulatory elements in the upstream regions of both genes. Exogenous sucrose (Suc) triggers impaired ethylene production in both mutants but is more severe in pdx1.3 than in pdx1.1. Interestingly, Suc specifically represses PDX1.1 expression, accounting for the stronger vitamin B6 deficit in pdx1.3 compared with pdx1.1. Surprisingly, Suc enhances auxin levels in pdx1.1, whereas the levels are diminished in pdx1.3. In the case of pdx1.3, the previously reported reduced meristem activity combined with the impaired ethylene and auxin levels manifest the specific root developmental defects. Moreover, it is the deficit in ethylene production and/or signaling that triggers this outcome. On the other hand, we hypothesize that it is the increased auxin content of pdx1.1 that is responsible for the root developmental defects observed therein. We conclude that PDX1.1 and PDX1.3 play partially nonredundant roles and are differentially regulated as manifested in disparate root growth impairment morphologies. PMID:25475669

Boycheva, Svetlana; Dominguez, Ana; Rolcik, Jakub; Boller, Thomas; Fitzpatrick, Teresa B

2015-01-01

328

Transcriptional repression of the interleukin-2 gene by vitamin D3: direct inhibition of NFATp/AP-1 complex formation by a nuclear hormone receptor.  

PubMed Central

T-lymphocyte proliferation is suppressed by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active metabolite of vitamin D3, and is associated with a decrease in interleukin 2 (IL-2), gamma interferon, and granulocyte-macrophage colony-stimulating factor mRNA levels. We report here that 1,25(OH)2D3-mediated repression in Jurkat cells is cycloheximide resistant, suggesting that it is a direct transcriptional repressive effect on IL-2 expression by the vitamin D3 receptor (VDR). We therefore examined vitamin D3-mediated repression of activated IL-2 expression by cotransfecting Jurkat cells with IL-2 promoter/reporter constructs and a VDR overexpression vector and by DNA binding. We delineated an element conferring both DNA binding by the receptor in vitro and 1,25(OH)2D3-mediated repression in vivo to a short 40-bp region encompassing an important positive regulatory element, NF-AT-1, which is bound by a T-cell-specific transcription factor, NFATp, as well as by AP-1. VDR DNA-binding mutants were unable to either bind to this element in vitro or repress in vivo; the VDR DNA-binding domain alone, however, bound the element but also could not repress IL-2 expression. These results indicate that DNA binding by VDR is necessary but not sufficient to mediate IL-2 repression. By combining partially purified proteins in vitro, we observed the loss of the bound NFATp/AP-1-DNA complex upon inclusion of VDR or VDR-retinoid X receptor. Order of addition and off-rate experiments indicate that the VDR-retinoid X receptor heterodimer blocks NFATp/AP-1 complex formation and then stably associates with the NF-AT-1 element. This direct inhibition by a nuclear hormone receptor of transcriptional activators of the IL-2 gene may provide a mechanistic explanation of how vitamin derivatives can act as potent immunosuppressive agents. PMID:7565732

Alroy, I; Towers, T L; Freedman, L P

1995-01-01

329

An unusual case of brown tumor of hyperparathyroidism associated with ectopic parathyroid adenoma  

PubMed Central

Brown tumor is a giant cell lesion associated with hyperparathyroidism. It is a non-neoplastic condition and represents terminal stage of the remodeling process in hyperparathyroid state. We report a case of brown tumor with multiple lesions in craniofacial region associated with ectopic parathyroid adenoma revealed after acute L-thyroxine poisoning. This case report emphasizes on the need for routine biochemical investigations along with serum calcium, phosphorus and parathyroid hormone levels in patients on thyroxine therapy. PMID:24932128

Mohan, Mathan; Neelakandan, Ravana Sundaram; Siddharth, D.; Sharma, Ravi

2013-01-01

330

Moderate endurance training has no effect on the parathyroid function of heart transplant patients  

Microsoft Academic Search

The benefit of retraining for heart transplant recipients (HTR) is now well established. The rehabilitation of these patients\\u000a can be compromised by osteopenia and bone fractures. The resting levels of parathyroid hormone (PTH) and exercise-induced\\u000a increases are higher in HTR than in healthy controls. To evaluate the effect of a moderate endurance training programme on\\u000a parathyroid activity, six HTR, an

Anne Charloux; Gabrielle Brandenberger; Eliane Lampert; Florian Chapotot; Claude Gronfier; Bertrand Mettauer; Bernard Geny; Jean Lonsdorfer

1997-01-01

331

Parathyroid changes after high dose radioactive iodine in patients with thyroid cancer  

Microsoft Academic Search

Objective  The study aimed to investigate the effect of high dose radioactive iodine (RAI) on parathyroid function in patients with differentiated\\u000a thyroid cancer.\\u000a \\u000a \\u000a \\u000a Methods  Nineteen patients (8 men\\/11 women, age 46.5 ± 13.2 years) undergoing RAI for thyroid remnant ablation were enrolled in the\\u000a study. The biochemical parameters related to parathyroid function [serum calcium (Ca), phosphate (P), creatinine (Cr), alkaline\\u000a phosphatase (ALP), intact parathyroid hormone

Aytekin Guven; Serpil Salman; Harika Boztepe; Sema Yarman; Refik Tanakol; Halil Azizlerli; Faruk Alagol

2009-01-01

332

Current status of parathyroid autotransplantation.  

PubMed

Autotransplantation of the parathyroid glands is a clinically useful modality for the management of patients with certain forms of hyperparathyroidism. In conjunction with total parathyroidectomy, this procedure has been used to treat patients with primary and secondary hyperparathyroidism who have generalized parathyroid hyperplasia. Parathyroid autotransplantation is also an important adjunct to the management of patients undergoing radical thyroid or laryngeal surgery to prevent permanent hypoparathyroidism from devascularization of all in situ parathyroid tissue. The technique of parathyroid cryopreservation has been well established and provides surgeons with greater flexibility in the approach to patients undergoing reoperative parathyroid surgery in whom there is uncertainty about the functional status of the remaining parathyroid tissue. Parathyroid allotransplantation has been successfully performed in immunosuppressed patients but is rarely indicated. Parathyroid autografts can be placed heterotopically in a forearm muscle or in the sternocleidomastoid, but the former site is preferred in patients with hyperplastic or adenomatous tissue. This technique results in a low incidence of permanent hypoparathyroidism after radical parathyroidectomy, and recurrent hypercalcemia can be easily managed by local excision of a portion of the grafted tissue. PMID:2180041

Brunt, L M; Sicard, G A

1990-01-01

333

A case of parathyroid adenoma adjacent to the thoracic spine in a hemodialysis patient.  

PubMed

Ectopic parathyroid glands are detected occasionally, especially in cases of recurrent hyperparathyroidism after initial parathyroidectomy. Their ectopic locations usually result from faulty migration during embryogenesis. Ectopic parathyroid glands can be found within the thyroid gland, thymus, mediastinum, carotid sheath, or retropharynx, which lie along the path of their normal migration. Here we report a rare case of parathyroid adenoma adjacent to the thoracic spine in a hemodialysis patient who had undergone parathyroidectomy previously. A 67-year-old woman on maintenance hemodialysis since 1993 developed hyperparathyroidism. She underwent total parathyroidectomy with autotransplantation in 2007. Histological examination of the parathyroid glands showed hyperplasia in three glands and adenoma in one. Serum parathyroid hormone levels gradually increased after a year. Ultrasonography of the neck and upper limbs was negative, but technetium-99-sestamibi scanning showed focal uptake in the posterior mediastinum. Computed tomography and magnetic resonance imaging confirmed a tumor adjacent to the left costovertebral junction of the third thoracic vertebra. A tumor resection was performed in 2010, and histopathological examination showed a parathyroid adenoma. Parathyroid adenoma adjacent to the thoracic spine has not been reported previously, and our case suggests that technetium-9-sestamibi scanning is useful for the correct preoperative diagnosis of such rare cases of ectopic parathyroid glands. PMID:22854163

Nakai, Kentaro; Fujii, Hideki; Maeno, Koichiro; Nishida, Kotaro; Kobayashi, Akira; Shin, Jeongsoo; Hara, Shigeo; Nishi, Shinichi

2014-01-01

334

Vitamin K2, a Naturally Occurring Menaquinone, Exerts Therapeutic Effects on Both Hormone-Dependent and Hormone-Independent Prostate Cancer Cells  

PubMed Central

In recent years, several studies have shown that vitamin k2 (VK2) has anticancer activity in a variety of cancer cells. The antitumor effects of VK2 in prostate cancer are currently not known. In the present study, we sought to characterize the anticancer potential of VK2 in both androgen-dependent and -independent prostate cancer cells. Our investigations show that VK2 is able to suppress viability of androgen-dependent and androgen-independent prostate cancer cells via caspase-3 and -8 dependent apoptosis. We also show that VK2 treatment reduces androgen receptor expression and PSA secretion in androgen-dependent prostate cancer cells. Our results also implicate VK2 as a potential anti-inflammatory agent, as several inflammatory genes are downregulated in prostate cancer cells following treatment with VK2. Additionally, AKT and NF-kB levels in prostate cancer cells are reduced significantly when treated with VK2. These findings correlated with the results of the Boyden chamber and angiogenesis assay, as VK2 treatment reduced cell migration and angiogenesis potential of prostate cancer cells. Finally, in a nude mice model, VK2 administration resulted in significant inhibition of both androgen-dependent and androgen-independent tumor growth. Overall, our results suggest that VK2 may be a potential therapeutic agent in the treatment of prostate cancer. PMID:24062781

Samykutty, Abhilash; Shetty, Aditya V.; Dakshinamoorthy, Gajalakshmi; Zheng, Gouxing; Chen, Aoshuang; Bosland, Maarten C.; Kajdacsy-Balla, André; Gnanasekar, Munirathinam

2013-01-01

335

Sequence elements in the human osteocalcin gene confer basal activation and inducible response to hormonal vitamin D sub 3  

SciTech Connect

Osteoblast-specific expression of the bone protein osteocalcin is controlled at the transcriptional level by the steroid hormone 1{alpha},25-dihydroxyvitamin D{sub 3}. As this protein may represent a marker for bone activity in human disease, the authors examined the regulation of its expression at the molecular level by evaluating human osteocalcin gene promoter function. They describe regions within the promoter that contribute to basal expression of the gene in osteoblast-like cells in culture. Further, they define a 21-base-pair DNA element with the sequence 5{prime}-GTGACTCACCGGGTGAACGGG-3{prime}, which acts in cis to mediate 1{alpha},25-dihydroxyvitamin D{sub 3} inducibility of the osteocalcin gene. This response element bears sequence similarity with other short DNA segments, particularly those for estrogen and thyroid hormone, which act together with their respective trans-acting receptors to modulate gene transcription.

Kerner, S.A.; Scott, R.A.; Pike, J.W. (Baylor College of Medicine, Houston, TX (USA))

1989-06-01

336

Improvement in glucose tolerance and beta-cell function in a patient with vitamin D deficiency during treatment with vitamin D.  

PubMed Central

Glucose metabolism was studied in a patient with vitamin D deficiency during its treatment with small doses of vitamin D. A continuous infusion of glucose test was performed to assess glucose tolerance and insulin sensitivity and beta-cell function were derived by mathematical modelling. Fasting glucose was 5.6 mmol/l and achieved glucose after the infusion was 10.4 mmol/l confirming diabetes. The test was repeated 0.5, 1, 3 and 5 months after starting treatment. Serum calcium increased glucose intolerance from 1.76 to 2.0, 2.08, 1.96 and 2.0 mmol/l, respectively; vitamin D reached supraphysiological levels initially and returned to normal levels, and parathyroid hormone levels were normalized. Her weight did not change during treatment. Glucose tolerance improved during treatment and achieved glucose was 9.4, 8.6, 9.2 and 9.0 mmol/l at 0.5, 1, 3 and 5 months, respectively; insulin sensitivity did not change. Beta-cell function improved from 101% at diagnosis to 126%, 147%, 173% and 198% at 0.5, 1, 3 and 5 months, respectively. Improvement in beta-cell function and consequently in glucose tolerance is likely to have been due to correction of hypocalcaemia, vitamin D deficiency and secondary hyperparathyroidism. PMID:8029165

Kumar, S.; Davies, M.; Zakaria, Y.; Mawer, E. B.; Gordon, C.; Olukoga, A. O.; Boulton, A. J.

1994-01-01

337

All the Parathyroids, All the Time: The Parathyroids, Basic and Clinical Concepts  

NASA Technical Reports Server (NTRS)

The second edition of The Parathyroids, Basic and Clinical Concepts is a comprehensive source of information that most endocrinologists will want to have on their bookshelves. Not only does it describe the basic physiology of the parathyroids, but also the clinical aspects of hyper- and hypoparathyroid states. The authors have retained the general organization of the first edition but have updated and revised all the sections and added a few new chapters. The list of authors is impressive, comprising the many students of G. Auerbach, whose laboratory isolated the hormone and whose untimely death ten years ago inspired the first edition of the book. The younger generation of scientists from several other laboratories, who have made significant contributions to parathyroid physiology and molecular genetics, are also included. Chapters about the presentation of clinical primary hyperparathyroidism in Europe, India, Brazil and China are of particular interest. Classic features of the disease are found that contrast with the often asymptomatic disease found in the West, which is discovered through modest increases in serum calcium from biochemical screening.

Arnaud, Sara B.

2003-01-01

338

Evaluation of parathyroid autograft growth and function in hemodialysis patients  

SciTech Connect

The aim of our study was to evaluate the function and growth of parathyroid tissue autografted into the forearm of hemodialysis patients using several presently available methods. In a dynamic study, the secretory function of autografted tissue was evaluated in seven patients using either zero calcium dialysate or calcium infusion. In an additional prospective study, seven patients had repeated determinations of plasma immunoreactive parathyroid hormone (iPTH) concentration on samples from both forearms, a radionuclide evaluation of autograft function using thallium-201 chloride, and real time ultrasonography. Light microscopy analysis was performed in two patients. The dynamic study demonstrated that induction of hypocalcemia was followed by an increase, and induction of hypercalcemia by a decrease in circulating iPTH in both forearms using three different radioimmunoassays similar to what has been reported for normal parathyroid tissue. A significant gradient (ie, greater than 2.0) of plasma iPTH concentration in samples from both forearms was observed in only three out of the seven patients of the prospective study. Two of these patients disclosed an increased uptake of /sup 201/TI chloride at the site of autografted tissue and had an echographically detectable mass. In both, hyperplastic parathyroid tissue was removed. At present, the remaining third patient does not have other features of recurrent hyperparathyroidism. In conclusion, autotransplanted parathyroid tissue of hemodialysis patients shows an adequate response to physiologic stimuli such as hypo- and hypercalcemia. Dynamic tests, therefore, appear to be a useful tool in the assessment of its function. In addition, radionuclide and echographic studies may be reliable adjuncts in the detection of marked parathyroid autograft hyperplasia.

Karsenty, G.; Petraglia, A.; Bourdeau, A.; Gambini, D.J.; Moreau, J.F.; Lecharpentier, Y.; Zingraff, J.; Bournerias, F.; Buisson, C.; Dubost, C.

1986-07-01

339

Intraoperative 3-D mapping of parathyroid adenoma using freehand SPECT  

PubMed Central

Background Freehand single photon emission computed tomography (fSPECT) is a three-dimensional (3-D) tomographic imaging modality based on data acquisition with a handheld detector that is moved freely, in contrast to conventional, gantry-mounted gamma camera systems. In this pilot study, we evaluated the feasibility of fSPECT for intraoperative 3-D mapping in patients with parathyroid adenomas. Methods Three patients (range 30 to 45 years) diagnosed with hyperparathyroidism (one primary and two tertiary) underwent parathyroid scintigraphy with technetium-99m sestamibi (99mTc-MIBI) to localize parathyroid adenomas. Two patients were referred with persistent hyperparathyroidism after conventional parathyroidectomy. In all three patients, a planar scintigraphy of the neck was performed 10 min after injection (p.i.) followed by SPECT/CT (Symbia T2, Siemens Healthcare) and a correlative ultrasound 2 h p.i. 99mTc-MIBI scan was performed the day before surgery in two patients and at the same day in one patient. fSPECT images were acquired intraoperatively using declipse SPECT (SurgicEyeTM). Results A total of five parathyroid adenomas were successfully located with SPECT/CT. fSPECT allowed intraoperative detection of all adenomas, and successful parathyroidectomy was accomplished. Parathyroid hormone level decreased intraoperatively in all three patients, on average, by 79% (range 72% to 91%). Conclusion In this preliminary study, we could demonstrate that intraoperative localization of parathyroid adenomas is feasible using the freehand SPECT technology, thus allowing an image-guided parathyroidectomy. PMID:23014191

2012-01-01

340

Vitamin D intoxication in two brothers: be careful with dietary supplements.  

PubMed

Vitamin D (VitD) intoxication, a well-known cause of hypercalcaemia in children, has renal, cardiac and neurological consequences. Iatrogenic or accidental administrations are the most common causes. We present two cases of hypervitaminosis D due to over-the-counter VitD supplement self-medication. A 12-year-old boy was hospitalised for abdominal pain, constipation and vomiting. Routine biochemistry indicated severe hypercalcaemia and renal failure. Plasma 25-OH VitD level was very high and parathyroid hormone was suppressed. Renal ultrasound showed nephrolithiasis. Hydration, diuretics and prednisone induced a progressive reduction of calcium levels. His brother, who was receiving the same treatment, was hospitalised although asymptomatic. Normal serum calcium and renal function were revealed, while 25-OH VitD was high and parathyroid hormone was suppressed. Renal ultrasound was within the normal range. Examination of the VitD content of the over-the-counter supplement revealed a higher amount than declared. VitD administration implies several risks and must be prescribed only when needed and under strict medical control. PMID:24670344

Conti, Giovanni; Chirico, Valeria; Lacquaniti, Antonio; Silipigni, Lorena; Fede, Claudia; Vitale, Agata; Fede, Carmelo

2014-07-01

341

Parathyroid adenoma in third pharyngeal pouch cyst as a rare case of primary hyperparathyroidism.  

PubMed

The primitive thymus and inferior parathyroid derive from the third branchial cleft. During embryonic development, these structures descend, reaching their final localisation. Third branchial cleft anomalies present usually as a fistula, abscess or cyst. However, there are no reports on parathyroid adenomas in the literature other than as a morphological possibility. We describe the case of a 47-year-old man, who had been diagnosed with arterial hypertension and who presented with a cervical mass at the edge of the lower third of the sternocleidomastoid muscle. On ultrasonography, the mass had a cystic walled appearance. Laboratory analysis only revealed an intact parathyroid hormone level of 140.5 pg/ml. Sestamibi imaging showed a probable parathyroid adenoma in the anterior mediastinum. During surgery, a tract running from beyond the superior thyroid pedicle to the superior mediastinum was dissected and removed. In the inferior end of the tract, a brown mass was visible. Pathological examination revealed a thymus cyst surrounding a parathyroid adenoma. The primal alteration was the lack of division between the thymus and inferior parathyroid gland, and the prompt prevention of their development. In the case of our patient, a parathyroid adenoma had grown by chance. PMID:25245714

Salido, S; Gómez-Ramírez, J; Bravo, J M; Martín-Pérez, E; Fernández-Díaz, G; Múñoz de Nova, J L; Auza, J; Larrañaga, E

2014-10-01

342

A Parathyroid Adenoma: Benign Disease Presenting with Hyperparathyroid Crisis  

PubMed Central

Hyperparathyroid crisis is a rare manifestation of parathyroid disease. We present the case of a 53-year-old gentleman with a review of the current literature. He presented in acute renal failure with epigastric pain and vomiting. His serum-corrected calcium (CCa2+) was raised at 5.2?mmol/L, in addition to a massively raised parathyroid hormone (PTH) level (3957?ng/L). Ultrasound studies of the neck revealed a 2?cm well-defined mass inferoposterior to right thyroid lobe. CT scans of the neck showed a normal mediastinum and confirmed no associated lymphadenopathy. Having undergone medical resuscitation for 9 days, a neck exploration revealed a cystic mass, which was excised. Histological investigations revealed a 9.25?g, cystic parathyroid adenoma with no features of malignancy. His PTH and CCa2+ returned to normal postoperatively. This suspicious presentation of benign disease, including a marked elevation in PTH, highlights the challenges facing the endocrine surgeon in dealing with parathyroid disease. PMID:21209735

Tahim, A. S.; Saunders, J.; Sinha, P.

2010-01-01

343

Locally recurrent parathyroid neoplasms as a cause for recurrent and persistent primary hyperparathyroidism.  

PubMed Central

Between 1982 and 1989, 145 patients underwent operations for persistent or recurrent primary hyperparathyroidism (HPT). At re-exploration, 15 patients (10.3%) were found to have locally recurrent parathyroid tumors (11 patients with adenoma and 4 with carcinoma). These 15 patients had 28 previous operations at outside institutions for HPT. Patients with locally recurrent HPT secondary to adenoma had a longer disease-free interval than patients with locally recurrent carcinoma. At the time of evaluation at the National Institutes of Health (NIH) for recurrent or persistent HPT, each patient was symptomatic and patients with carcinoma had significantly more symptoms and higher serum levels of calcium and parathyroid hormone than patients with adenoma. Locally recurrent parathyroid neoplasm was correctly localized by preoperative testing in 14 of 15 patients. These 15 patients underwent 18 reoperations at NIH for excision of locally recurrent parathyroid tumors. Following the final reoperation (two patients had more than one procedure), each patient had normal serum levels of calcium. In addition each patient remains biochemically cured (based on normal serum calcium level), with a median follow-up interval of 21 months. Local recurrence of parathyroid adenoma comprises a small but significant proportion of cases of recurrent or persistent HPT and can be indistinguishable from parathyroid carcinoma. Findings suggestive of carcinoma include shorter disease-free interval, higher serum levels of calcium and parathyroid hormone, and histologic appearance. Whether the locally recurrent parathyroid neoplasm is benign or malignant, aggressive surgery can control serum levels of calcium in these patients with acceptable rates of morbidity. PMID:1985539

Fraker, D L; Travis, W D; Merendino, J J; Zimering, M B; Streeten, E A; Weinstein, L S; Marx, S J; Spiegel, A M; Aurbach, G D; Doppman, J L

1991-01-01

344

Parathyroid nuclear scan. A focused review on the technical and biological factors affecting its outcome  

PubMed Central

Summary Objective Technetium Parathyroid Scintigraphy (TS) is the most popular noninvasive localization procedure in patients with primary hyperparathyroidism (PHPT). Awareness of various factors involved in technetium uptake helps understand the outcome of TS. Methods We utilize a case of changing TS scans in a patient to review the literature on the various biological and technical factors involved in technetium uptake by the abnormal parathyroid tissue. A 56 year female was diagnosed with PHPT and osteopenia. An initial scan using 99mTc-Tetrofosmin showed no definite areas of abnormal parathyroid tissue. Patient refused surgical exploration, was started on Bisphosponates and subsequently monitored. Five years later she suffered fracture of her right wrist. A repeat TS using 99mTc-Sestamibi revealed hypervascular parathyroid lesion in the right lower neck. She underwent successful removal of a right lower parathyroid adenoma. Results Technical factors like the type of Tc isotope used, imaging techniques and biological factors like biochemical parameters (calcium, vitamin D levels), adenoma size, content of oxyphilic cells, vascularity can affect the outcome of the scan. Conclusion Clinicians should be aware of technical and biological factors that could result in negative scan in parathyroid nuclear scintigraphy. PMID:25002876

Kannan, Subramanian; Milas, Mira; Neumann, Donald; Parikh, Rikesh T.; Siperstein, Alan; Licata, Angelo

2014-01-01

345

The status of Vitamin D in medical students in the preclerkship years of a Saudi medical school  

PubMed Central

Background: The prevalence of vitamin D deficiency has recently been recognized in different parts of the world, even affecting healthy populations. The deficiency of vitamin D can lead to rickets in children and osteomalacia in adults. Few studies have been done to evaluate the status of vitamin D in the medical community. The objective of this study was to evaluate the prevalence of low levels of vitamin D in healthy Saudi medical students. Materials and Methods: A cross-sectional study was carried out in November 2009 on male and female students in the preclerkship years of medical school at the King Faisal University, Dammam. Data on age, consumption of dairy products and seafood, and exposure to sunlight were collected. The body mass index was calculated. Approximately, 15 ml of blood was extracted for the measurement of serum calcium, serum albumin, serum phosphorus, alkaline phosphatase, fasting parathyroid hormone, and vitamin D levels. Vitamin D deficiency was defined as serum 25-hydroxy vitamin D < 50 nmol/l. Comparison between groups was done for statistical significance using an unpaired t-test. Significance was set at P < 0.05 using 95% CI for all comparisons. Results: The data from 95 male and 103 female students were analyzed. The mean age for all students was 19.54 years. In 100% of the students, the vitamin D level was low. The prevalence of vitamin D deficiency in all students was 96.0% (92.64% in males and 99.03% in females), while the remaining 4% had vitamin D insufficiency. The mean 25-hydroxy vitamin D level was 26.83 ± 12.60 nmol/l in males and 16.03 ± 8.28 nmol/l in females (P-value = 0.0001). Males had a statistically significant higher body mass index as well as consumption of dairy products, while the consumption of seafood was significantly higher in females. There was no difference between the two groups in terms of exposure to the sun. Conclusion: Vitamin D deficiency was highly prevalent among medical students included in this study. An urgent action has to be taken in order to prevent adverse consequences of low vitamin D in the young, otherwise healthy populations. PMID:22870413

Al-Elq, Abdulmohsen H.

2012-01-01

346

Prevalence of hypovitaminosis D and predictors of vitamin D status in Italian healthy adolescents  

PubMed Central

Background Vitamin D plays an important role in health promotion during adolescence. Vitamin D deficiency and insufficiency are common in adolescents worldwide. Few data on vitamin D status and risk factors for hypovitaminosis D in Italian adolescents are currently available. Methods 25-hydroxyvitamin D (25-OH-D) and parathyroid hormone (PTH) levels were evaluated in 427 Italian healthy adolescents (10.0-21.0 years). We used the following cut-off of 25-OH-D to define vitamin D status: deficiency?vitamin D deficiency as 25-OH-D levels?vitamin D status. Results Enrolled adolescents had a median serum 25-OH-D level of 50.0 nmol/L, range 8.1-174.7, with 82.2% having hypovitaminosis D. Vitamin D deficiency and insufficiency were detected in 49.9% and 32.3% of adolescents, respectively. Among those with deficiency, 38 subjects were severely deficient (38/427, 8.9% of the entire sample). Non-white adolescents had a higher prevalence of severe vitamin D deficiency than white subjects (6/17-35.3% vs 32/410-7.8% respectively, p?=?0.002). Logistic regression showed increased risk of hypovitaminosis D as follows: blood withdrawal taken in winter-spring (Odds ratio (OR) 5.64) compared to summer-fall period; overweight-obese adolescents (OR 3.89) compared to subjects with normal body mass index (BMI); low sun exposure (OR 5.94) compared to moderate-good exposure and regular use of sunscreens (OR 5.89) compared to non regular use. Adolescents who performed?vitamin D status. Serum 25-OH-D levels were inversely related to PTH (r?=?-0.387, p?vitamin D deficiency and insufficiency. Pediatricians should tackle predictors of vitamin D status, favoring a healthier lifestyle and promoting supplementation in the groups at higher risk of hypovitaminosis D. PMID:24902694

2014-01-01

347

Vitamin D deficiency in HIV-infected postmenopausal Hispanic and African-American women  

PubMed Central

Summary We evaluated vitamin D status in HIV+ and HIV? postmenopausal African-American (AA) and Hispanic women. Most women (74–78%) had insufficient 25-hydroxyvitamin D (25OHD) levels, regardless of HIV status. 25OHD was lower in AA women and women lacking supplement use, providing support for screening and supplementation. Among HIV+ women, 25OHD was associated with current CD4 but not type of antiretroviral therapy. Introduction To evaluate vitamin D status and factors associated with vitamin D deficiency and insufficiency in HIV-infected (HIV+) postmenopausal minority women. Methods In this cross-sectional study, 89 HIV+ and 95 HIV? postmenopausal women (33% AA and 67% Hispanic) underwent assessment of 25OHD, 1,25-dihydroxyvitamin D, parathyroid hormone, markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry. Results The prevalence of low 25OHD did not differ by HIV status; the majority of both HIV+ and HIV? women (74–78%) had insufficient levels (<30 ng/ml). Regardless of HIV status, 25OHD was significantly lower in AA subjects, and higher in subjects who used both calcium and multi-vitamins. In HIV+ women on antiretroviral therapy (ART), 25OHD was directly associated with current CD4 count (r= 0.32; p<0.01) independent of age, ethnicity, BMI, or history of AIDS-defining illness. No association was observed between 1,25(OH)2D and CD4 count or between serum 25OHD, 1,25(OH)2D or PTH and type of ART. Conclusions In postmenopausal minority women, vitamin D deficiency was highly prevalent and associated with AA race and lack of supplement use, as well as lower current CD4 cell count. These results provide support for screening and repletion of vitamin D in HIV+ patients. PMID:20585939

Stein, E. M.; McMahon, D. J.; Shu, A.; Zhang, C. A.; Ferris, D. C.; Colon, I.; Dobkin, J. F.; Hammer, S. M.; Shane, E.

2011-01-01

348

Primary hyperparathyroidism and metabolic risk factors, impact of parathyroidectomy and vitamin D supplementation, and results of a randomized double-blind study  

PubMed Central

Background Vitamin D insufficiency may increase the risk for cardio metabolic disturbances in patients with primary hyperparathyroidism (PHPT). Objective To analyze the vitamin D status and indices of the metabolic syndrome in PHPT patients and the effect of vitamin D supplementation after parathyroid adenomectomy (PTX). Design and methods Double-blinded, randomized clinical trial (ClinicalTrials.gov Identifier: NCT00982722) performed at Karolinska University Hospital, Sweden, April 2008 to November 2011. One hundred and fifty consecutive patients with PHPT (119 women) were randomized after PTX, 75 to oral treatment with calcium carbonate 1000?mg daily and 75 to calcium carbonate 1000?mg and cholecalciferol 1600?IU daily over 12 months. Changes in metabolic profile and ambulatory blood pressure (BP) were analyzed. Main outcome measures were changes in metabolic factors, BP, and body composition. Results The 25-hydroxyvitamin D (25-OH-D)-level was <50?nmol/l in 76% of the patients before PTX. After PTX, glucose, insulin, and IGF1 decreased, while the 25-OH-D and the IGF-binding protein 1 increased and remained unchanged at follow-up after study medication. One year of vitamin D supplementation resulted in lower parathyroid hormone (PTH) (40 (34–52) vs 49 (38–66) ng/l) and higher 25-OH-D (76 (65–93) vs 49 (40–62) nmol/l; P<0.05). Other laboratory parameters were stable compared with after PTX. Systolic BP decreased and total bone mineral content increased in both groups. Conclusion Except for the lowering of the PTH level, no additive effect of vitamin D supplementation was seen. However, PTX proved effective in reducing insulin resistance. PMID:24026893

Norenstedt, Sophie; Pernow, Ylva; Brismar, Kerstin; Sääf, Maria; Ekip, Ayla; Granath, Fredrik; Zedenius, Jan; Nilsson, Inga-Lena

2013-01-01

349

[Mediastinal parathyroid adenoma: a surgically treated case].  

PubMed

Sixteen percent of primary hyperparathyroidism is caused by ectopic parathyroid glands. These cases present diagnostic and therapeutic challenges. In this article we present the case of a patient underwent surgery for a mediastinal parathyroid adenoma causing symptomatic hypercalcaemia. PMID:23955953

Mészáros, László; Kajdácsi, Zita; Tóth, Miklós; Révai, Tamás; Vadász, Pál

2013-08-01

350

Reduced serum concentrations of 25-hydroxy vitamin D in Egyptian patients with systemic lupus erythematosus: Relation to disease activity  

PubMed Central

Summary Background Recently, vitamin D deficiency has been implicated as a potential environmental factor triggering some autoimmune disorders, including systemic lupus erythematosus (SLE)). In addition, patients with SLE, especially those with increased disease activity, were suggested to have decreased vitamin D level, suggesting that vitamin D might play a role in regulating autoantibody production. Material/Methods To assess 25 hydroxy vitamin D [25(OH)D] status in Egyptian patients with SLE and its relation to disease activity. Clinical evaluation and assay of serum 25(OH)D, total calcium, phosphorous, alkaline phosphatase (ALP) and parathyroid hormone (PTH) were done on 60 SLE patients in comparison to 60 matched-healthy subjects. Serum 25(OH)D levels <30 and 10 ng/ml were defined as vitamin D insufficiency and deficiency, respectively. Results Serum 25(OH)D was significantly lower in patients than in controls (26.33±12.05 vs. 42.66±9.20 respectively, p<0.0001), with 13.30% and 60% being deficient and insufficient, respectively. Serum 25(OH)D levels were lower with increased disease activity (p=0.03) and frequency of photosensitivity(p=0.02) and photoprotection (p=0.002). Systemic lupus erythematosus disease activity index (SLEDAI) score (OR: 2.72, 95% CI: 1.42–5.18, P=0.002), photosensitivity (OR: 3.6, 95% CI: 1.9–6.8, P<0.01) and photoprotection (OR: 6.7, 95% CI: 2.9–8.8, P<0.001) were significant predictors of 25(OH)D level among SLE cases. Conclusions Low vitamin D status is prevalent in Egyptian SLE patients despite plentiful exposure to sunlight throughout the year, and its level is negatively correlated to disease activity. Future studies looking at a potential role of vitamin D in the pathophysiology and treatment of SLE are warranted. PMID:22129903

Hamza, Rasha T.; Awwad, Khaled S.; Ali, Mohamed K.; Hamed, Amira I.

2011-01-01

351

[Intrathyroidal parathyroid adenoma. Study of a case].  

PubMed

Intrathyroidal parathyroid adenoma is an infrequent lesion which can be explained by abnormalities during embryonic migration of the parathyroid glands. That abnormality can be a cause of failed cervical exploration for primary hyperparathyroidism. From a case report and literature data, we propose an exploration processes to search those ectopic parathyroid adenoma. PMID:15277980

Guinier, D; Delroeux, D; Viennet, G; Mantion, G A

2004-05-01

352

Vitamin D supplementation and calcium absorption during caloric restriction: a randomized double-blind trial123  

PubMed Central

Background: Weight loss (WL) is associated with a decrease in calcium absorption and may be one mechanism that induces bone loss with weight reduction. Objective: Because vitamin D supplementation has been shown to increase true fractional calcium absorption (TFCA), the goal of this study was to examine the effect of vitamin D during WL or weight maintenance (WM). Design: A randomized, placebo-controlled, double-blind 6-wk study was conducted in 82 postmenopausal women [BMI (in kg/m2; ±SD): 30.2 ± 3.7] with 25-hydroxyvitamin D [25(OH)D] concentrations <70 nmol/L during either WL or WM. All women were given 10 ?g vitamin D3/d and 1.2 g Ca/d and either weekly vitamin D3 (375 ?g) or a placebo equivalent to 63 ?g (2500 IU)/d and 10 ?g (400 IU)/d, respectively. We measured TFCA with the use of dual-stable isotopes, 25(OH)D, parathyroid hormone, estradiol, calcitriol, and urinary calcium at baseline and 6 wk in weight loss and vitamin D3–supplementation (WL-D; n = 19), weight maintenance and vitamin D3–supplementation (WM-D; n = 20), weight loss and placebo (n = 22), and weight maintenance and placebo (n = 21) groups. Results: WL groups lost 3.8 ± 1.1% of weight with no difference between vitamin D3 supplementation and the placebo. The rise in serum 25(OH)D was greatest in the WL-D group (19.8 ± 14.5 nmol/L) compared with in WM-D (9.1 ± 10.3 nmol/L) and placebo groups (1.5 ± 10.9 nmol/L). TFCA increased with vitamin D3 supplementation compared with placebo treatment (P < 0.01) and decreased during WL compared with WM. Serum 25(OH)D or 1,25-dihyroxyvitamin D did not correlate with TFCA. Conclusion: These data show that vitamin D supplementation increases TFCA and that WL decreases TFCA and suggest that, when calcium intake is 1.2 g/d, either 10 or 63 ?g vitamin D/d is sufficient to maintain the calcium balance. This trial was registered at clinicaltrials.gov as NCT00473031. PMID:23364004

Shapses, Sue A; Sukumar, Deeptha; Schneider, Stephen H; Schlussel, Yvette; Sherrell, Robert M; Field, M Paul; Ambia-Sobhan, Hasina

2013-01-01

353

The bovine renal parathyroid hormone (PTH) receptor has equal affinity for two different amino acid sequences: the receptor binding domains of PTH and PTH-related protein are located within the 14-34 region.  

PubMed

Previous studies examining the interaction of PTH and PTH-related protein (PTHrP) with target tissue have for the most part emphasized the similarity between the two hormones in binding to and activating receptors. This observation that two peptides with limited homology have equal affinities for the same receptor is unusual. In this report we investigated two aspects of PTH/PTHrP-receptor interactions. First, the nonhomologous 14-34 regions of PTH and PTHrP were synthesized and evaluated. Second, hybrid peptides containing the 7-18 fragment of one hormone combined with the 19-34 region of the other hormone were studied to determine whether interactions between these two regions are required for receptor recognition. All four peptides were examined in bovine renal cortical membrane and rat osteosarcoma (ROS 17/2.8) cell PTH-binding and PTH-stimulated adenylate cyclase assays. The results indicate that the receptor-binding domains of PTH and PTHrP lie outside of the 1-13 region, the region containing sequence homology shared by the two hormones, and that two peptides of different amino acid sequence bind with equal affinity to the bovine renal PTH receptor. However, in the absence of the N-terminal region, the rat bone PTH receptor displays a preference for the C-terminal (19-34 sequence) region of PTHrP. PMID:2163327

Caulfield, M P; McKee, R L; Goldman, M E; Duong, L T; Fisher, J E; Gay, C T; DeHaven, P A; Levy, J J; Roubini, E; Nutt, R F

1990-07-01

354

Vitamin A  

MedlinePLUS

... QuickFacts Datos en español Health Professional Other Resources Vitamin A Fact Sheet for Consumers What is vitamin A and what does it do? Vitamin A ... out more about vitamin A? Disclaimer How much vitamin A do I need? The amount of vitamin ...

355

Vitamin E  

MedlinePLUS

... Datos en español Health Professional Other Resources Vitamin E Fact Sheet for Consumers What is vitamin E and what does it do? Vitamin E is ... more about vitamin E? Disclaimer How much vitamin E do I need? The amount of vitamin E ...

356

Increased anxiety in mice lacking vitamin D receptor gene  

E-print Network

Increased anxiety in mice lacking vitamin D receptor gene Allan V. Kalue¡,1,CA Yan-Ru Lou,1 Ilkka.0000129370.04248.92 Vitamin D is a steroid hormone with many important functions in the brain, mediated through the vitamin D nuclear receptor. Nu- merous human and animal data link vitamin D dysfunctions

Kalueff, Allan V.

357

Vitamin D safety and requirements.  

PubMed

Vitamin D an ancient secosteroid is essential for mineral homeostasis, bone remodeling, immune modulation, and energy metabolism. Recently, debates have emerged about the daily vitamin D requirements for healthy and elderly adults, the safety and efficacy of long term supplementation and the role of vitamin D deficiency in several chronic disease states. Since this molecule acts as both a vitamin and a hormone, it should not be surprising that the effects of supplementation are multi-faceted and complex. Yet despite significant progress in the last decade, our understanding of vitamin D physiology and the clinical relevance of low circulating levels of this vitamin remains incomplete. The present review provides the reader with a comprehensive and up-to-date understanding of vitamin D requirements and safety. It also raises some provocative research questions. PMID:22179017

de Paula, Francisco J A; Rosen, Clifford J

2012-07-01

358

Vitamin D supplementation in older people (VDOP): Study protocol for a randomised controlled intervention trial with monthly oral dosing with 12,000 IU, 24,000 IU or 48,000 IU of vitamin D3  

PubMed Central

The randomised, double blind intervention trial ‘Optimising Vitamin D Status in Older People’ (VDOP) will test the effect of three oral dosages of vitamin D given for one year on bone mineral density (BMD) and biochemical markers of vitamin D metabolism, bone turnover and safety in older people. VDOP is funded by Arthritis Research UK, supported through Newcastle University and MRC Human Nutrition Research and sponsored by the Newcastle upon Tyne Hospitals NHS Foundation Trust.a Background Vitamin D insufficiency is common in older people and may lead to secondary hyperparathyroidism, bone loss, impairment of muscle function and increased risk of falls and fractures. Vitamin D supplementation trials have yielded conflicting results with regard to decreasing rates of bone loss, falls and fractures and the optimal plasma concentration of 25 hydroxy vitamin D (25OHD) for skeletal health remains unclear. Method/design Older (?70 years) community dwelling men and women are recruited through General Practices in Northern England and 375 participants are randomised to take 12,000 international units (IU), 24,000 IU or 48,000 IU of vitamin D3 orally each month for one year starting in the winter or early spring. Hip BMD and anthropometry are measured at baseline and 12 months. Fasting blood samples are collected at baseline and three-month intervals for the measurement of plasma 25OHD, parathyroid hormone (PTH), biochemical markers of bone turnover and biochemistry to assess the dose–response and safety of supplementation. Questionnaire data include falls, fractures, quality of life, adverse events and outcomes, compliance, dietary calcium intake and sunshine exposure. Discussion This is the first integrated vitamin D supplementation trial in older men and women using a range of doses given at monthly intervals to assess BMD, plasma 25OHD, PTH and biochemical markers of bone turnover and safety, quality of life and physical performance. We aim to investigate the vitamin D supplementation and plasma 25OHD concentration required to maintain bone health and to develop a set of biochemical markers that reflects the effect of vitamin D on bone. This will aid future studies investigating the effect of vitamin D supplementation on fracture risk. #ISRCTN 35648481 (assigned 16 August 2012), EudraCT 2011-004890-10.

2013-01-01

359

Treatment of vitamin D deficiency with UV light in patients with malabsorption syndromes: a case series  

PubMed Central

Background Cystic fibrosis (CF) and short bowel syndrome (SBS) patients are unable to absorb vitamin D from the diet and thus are frequently found to be severely vitamin D deficient. We evaluated whether a commercial portable ultraviolet (UV) indoor tanning lamp that has a spectral output that mimics natural sunlight could raise circulating 25-hydroxyvitamin D [25(OH)D] levels in subjects with CF and SBS. Methods In initial pilot studies, two SBS subjects came to the outpatient clinic twice weekly for 8 weeks for UV light sessions of 6 min each. In a follow-up study, five CF subjects exposed their lower backs in a seated position to the sunlamp at a distance of 14 cm for 5–10 min depending on the skin type five times a week for 8 weeks. Blood samples for 25(OH)D and parathyroid hormone (PTH) measurements were performed at baseline and at the end of the study. Results In our study, with two SBS subjects, the indoor lamp increased or maintained circulating 25(OH)D levels during the winter months. We increased the UV lamp frequency and found an improved response in the CF patients. Serum 25(OH)D levels in CF subjects at baseline were 21 ± 3 ng/ml, which increased to 27 ± 4 ng/ml at the end of 8 weeks (P = 0.05). PTH concentration remained largely unchanged in both population groups. Conclusion A UV lamp that emits ultraviolet radiation similar to sunlight and thus produces vitamin D3 in the skin is an excellent alternative for CF, and SBS patients who suffer from vitamin D deficiency due to fat malabsorption, especially during the winter months when natural sunlight is unable to produce vitamin D3 in the skin. This UV lamp is widely available for commercial home use and could potentially be prescribed to patients with CF or SBS. PMID:17803596

Chandra, Prakash; Wolfenden, Linda L.; Ziegler, Thomas R.; Tian, Junqiang; Luo, Menghua; Stecenko, Arlene A.; Chen, Tai C.; Holick, Michael F.; Tangpricha, Vin

2010-01-01

360

Vitamin D receptor gene polymorphisms in relation to Vitamin D related disease states  

Microsoft Academic Search

The role in skeletal metabolism of the steroid hormone Vitamin D and its nuclear receptor (VDR) is well known. In addition, however, Vitamin D is also involved in a wide variety of other biological processes including modulation of the immune response and regulation of cell proliferation and differentiation. Variations in the Vitamin D endocrine system have thus been linked to

André G. Uitterlinden; Yue Fang; Joyce B. J. van Meurs; Hans van Leeuwen; Huibert A. P. Pols

2004-01-01

361

VITAMIN D AND LIVING IN NORTHERN LATITUDES - AN ENDEMIC RISk AREA FOR VITAMIN D DEFICIENCy  

Microsoft Academic Search

Objectives. To review the current literature on the health effects of vitamin D, especially the effects on inhabitants living in the northern latitudes. Study Design. Literature review. Methods. The scientific literature concerning health effects of vitamin D was reviewed and the current dietary recommendations for inhabitants living in northern latitudes were discussed. Results. Vitamin D is a steroid-structured hormone produced

Anne Huotari; Karl-Heinz Herzig

362

Phosphatonins: new hormones involved in numerous inherited bone disorders  

PubMed Central

Summary Phosphate (Pi) homeostasis is under control of several endocrine factors that play effects on bone, kidney and intestine. The control of Pi homeostasis has a significant biological importance, as it relates to numerous cellular mechanisms involved in energy metabolism, cell signaling, nucleic acid synthesis, membrane function, as well as skeletal health and integrity. Pi is essential for diverse biological processes, and negative Pi balance resulting from improperly regulated intestinal absorption, systemic utilization, and renal excretion. As results of these functions, chronic Pi deprivation causes several biological alterations, such as bone demineralization with unmineralized osateoid typical of osteomalacia in adults and rickets in developing animals and humans (1). Phosphatonins are new hormones playing an important role in the control of Pi homeostasis together with parathyroid hormone (PTH) and 1,25-dihydroxy vitamin D3. Most insight into the underlying mechanisms was established by defining the molecular basis of different inherited disorders that are characterized by an abnormal regulation of Pi homeostasis. PMID:22461821

Masi, Laura

2011-01-01

363

The parathyroid hormone-regulated transcriptome in osteocytes: Parallel actions with 1,25-dihydroxyvitamin D3 to oppose gene expression changes during differentiation and to promote mature cell function.  

PubMed

Although localized to the mineralized matrix of bone, osteocytes are able to respond to systemic factors such as the calciotropic hormones 1,25(OH)2D3 and PTH. In the present studies, we examined the transcriptomic response to PTH in an osteocyte cell model and found that this hormone regulated an extensive panel of genes. Surprisingly, PTH uniquely modulated two cohorts of genes, one that was expressed and associated with the osteoblast to osteocyte transition and the other a cohort that was expressed only in the mature osteocyte. Interestingly, PTH's effects were largely to oppose the expression of differentiation-related genes in the former cohort, while potentiating the expression of osteocyte-specific genes in the latter cohort. A comparison of the transcriptional effects of PTH with those obtained previously with 1,25(OH)2D3 revealed a subset of genes that was strongly overlapping. While 1,25(OH)2D3 potentiated the expression of osteocyte-specific genes similar to that seen with PTH, the overlap between the two hormones was more limited. Additional experiments identified the PKA-activated phospho-CREB (pCREB) cistrome, revealing that while many of the differentiation-related PTH regulated genes were apparent targets of a PKA-mediated signaling pathway, a reduction in pCREB binding at sites associated with osteocyte-specific PTH targets appeared to involve alternative PTH activation pathways. That pCREB binding activities positioned near important hormone-regulated gene cohorts were localized to control regions of genes was reinforced by the presence of epigenetic enhancer signatures exemplified by unique modifications at histones H3 and H4. These studies suggest that both PTH and 1,25(OH)2D3 may play important and perhaps cooperative roles in limiting osteocyte differentiation from its precursors while simultaneously exerting distinct roles in regulating mature osteocyte function. Our results provide new insight into transcription factor-associated mechanisms through which PTH and 1,25(OH)2D3 regulate a plethora of genes important to the osteoblast/osteocyte lineage. PMID:25460572

St John, Hillary C; Meyer, Mark B; Benkusky, Nancy A; Carlson, Alex H; Prideaux, Mathew; Bonewald, Lynda F; Pike, J Wesley

2015-03-01

364

Vitamin D receptor agonists increase klotho and osteopontin while decreasing aortic calcification in mice with chronic kidney disease fed a high phosphate diet  

PubMed Central

Vascular calcification is common in chronic kidney disease, where cardiovascular mortality remains the leading cause of death. Patients with kidney disease are often prescribed vitamin D receptor agonists (VDRAs) that confer a survival benefit, but the underlying mechanisms remain unclear. Here we tested two VDRAs in a mouse chronic kidney disease model where dietary phosphate loading induced aortic medial calcification. Mice were given intraperitoneal calcitriol or paricalcitol three times per week for three weeks. These treatments were associated with half of the aortic calcification compared to no therapy, and there was no difference between the two agents. In the setting of a high phosphate diet, serum parathyroid hormone and calcium levels were not significantly altered by treatment. VDRA therapy was associated with increased serum and urine klotho levels, increased phosphaturia, correction of hyperphosphatemia, and lowering of serum fibroblast growth factor-23. There was no effect on elastin remodeling or inflammation, however, the expression of the anti-calcification factor, osteopontin, in aortic medial cells was increased. Paricalcitol upregulated osteopontin secretion from mouse vascular smooth muscle cells in culture. Thus, klotho and osteopontin were upregulated by VDRA therapy in chronic kidney disease, independent of changes in serum parathyroid hormone and calcium. PMID:22932118

Lau, Wei Ling; Leaf, Elizabeth M.; Hu, Ming Chang; Takeno, Marc M.; Kuro-o, Makoto; Moe, Orson W.; Giachelli, Cecilia M.

2012-01-01

365

Effect of adjuvant endocrine therapy on hormonal levels in premenopausal women with breast cancer: the ProBONE II study.  

PubMed

Endocrine therapy (ET) is a key treatment modality in hormone receptor positive (HR+) early breast cancer (BC) patients. Although the anticancer activity of adjuvant ET + zoledronic acid (ZOL) has been investigated, the potential effects of ET ± ZOL on endocrine hormones in premenopausal women with HR+ early BC are not well understood. ProBONE II was prospective, double-blind, randomized controlled trial. Premenopausal patients with histologically confirmed invasive BC with no evidence of metastases and a T score >-2.5 received ET ± ZOL 4 mg every 3 months for 2 years. Serum levels of estradiol (E2), follicle-stimulating hormone, anti-muellerian hormone (AMH), inhibins A and B, sex hormone-binding globulin, parathyroid hormone, total testosterone, and vitamin D were evaluated at baseline and at every scheduled visit. Of 71 women enrolled, 70 were evaluable (n = 34, ZOL; n = 36, placebo). No statistically significant differences were observed in hormone levels, except E2 and AMH, which showed minor differences. These included decreases in serum E2 levels, which reached a nadir after 3 and 9 months in placebo and ZOL groups, respectively, and decrease in serum AMH levels throughout the study with ZOL, but remained constant with placebo after 6 months. Adverse events in ZOL-treated group were influenza-like illness (32.4 %), bone pain (32.4 %), chills (20.6 %), and nausea (23.5 %). ET ± ZOL was well tolerated. This study showed no influence of ZOL on hormonal level changes that accompany ET, supporting inclusion of ZOL in adjuvant therapy for premenopausal women with HR + BC. PMID:24519387

Hadji, Peyman; Kauka, Annette; Ziller, May; Birkholz, Katrin; Baier, Monika; Muth, Mathias; Kann, Peter

2014-04-01

366

Vitamin D  

MedlinePLUS

... News Anxiety Disorders Relaxation Exercises The Flu Vaccine Vitamin D KidsHealth > Teens > Food & Fitness > Nutrition Basics > Vitamin ... get the recommended daily amount. Continue How Much Vitamin D Do I Need? The Institute of Medicine ( ...

367

Thoracoscopic Removal of Ectopic Mediastinal Parathyroid Adenoma  

PubMed Central

Ectopic mediastinal parathyroid adenomas or hyperplasias account for up to 25% of primary hyperparathyroidism cases. Most abnormal parathyroid glands are found in the superior mediastinum within the thymus and can be removed through a cervical incision; however, a few of these glands are not accessible using standard cervical surgical approaches. Surgical resection has traditionally been performed via median sternotomy or thoracotomy. However, recent advancement in video-assisted thoracic surgery techniques has decreased the need for sternotomy or thoracotomy to remove these ectopic parathyroid glands. Here, we report a successful case of video-assisted thoracoscopic removal of a mediastinal parathyroid adenoma. PMID:25207237

Kim, Young Su; Kim, Jhingook; Shin, Sumin

2014-01-01

368

PTH/PTHrP and Vitamin D Control Antimicrobial Peptide Expression and Susceptibility to Bacterial Skin Infection  

PubMed Central

The production of antimicrobial peptides is essential for protection against a wide variety of microbial pathogens and plays an important role in the pathogenesis of several diseases. The mechanisms responsible for expression of antimicrobial peptides are incompletely understood, but a role for vitamin D as a transcriptional inducer of the antimicrobial peptide cathelicidin has been proposed. We show that 1,25-dihydroxyvitamin D3 (1,25-D3) acts together with parathyroid hormone (PTH), or the shared amino-terminal domain of PTH-related peptide (PTHrP), to synergistically increase cathelicidin and immune defense. Administration of PTH to mouse skin decreased susceptibility to skin infection by group A Streptococcus. Mice on dietary vitamin D3 restriction that responded with an elevation in PTH have an increased risk of infection if they lack 1,25-D3. These results identify PTH/PTHrP as a variable that serves to compensate for inadequate vitamin D during activation of antimicrobial peptide production. PMID:22623742

Muehleisen, Beda; Bikle, Daniel D.; Aguilera, Carlos; Burton, Douglas W.; Sen, George L.; Deftos, Leonard J.; Gallo, Richard L.

2013-01-01

369

Parathyroid Scintigraphy in Renal Hyperparathyroidism  

PubMed Central

Secondary hyperparathyroidism (sHPT) is a major complication for patients with end-stage renal disease on long-term hemodialysis or peritoneal dialysis. When the disease is resistant to medical treatment, patients with severe sHPT are typically referred for parathyroidectomy (PTx), which usually improves biological parameters as well as clinical signs and symptoms. Unfortunately, early surgical failure with persistent disease may occur in 5%–10% of patients and recurrence reaches 20%–30% at 5 years. Presently, the use of parathyroid scintigraphy in sHPT is usually limited to the management of surgical failures after initial PTx. This review describes the strengths and limitations of typical 99mTc-sestamibi imaging protocols, and highlights the potential benefits of using parathyroid scintigraphy in the initial workup of surgical patients. PMID:23751837

Taïeb, David; Ureña-Torres, Pablo; Zanotti-Fregonara, Paolo; Rubello, Domenico; Ferretti, Alice; Henter, Ioline; Henry, Jean-François; Schiavi, Francesca; Opocher, Giuseppe; Blickman, Johan G.; Colletti, Patrick M.; Hindié, Elif

2015-01-01

370

A novel non-surgical, minimally invasive technique for parathyroid autotransplantation: A case report.  

PubMed

We present a case report of intramuscular autotransplantation of the parathyroid cell suspension acquired after total parathyroidectomy. A 15-yr-old female patient who had been undergoing hemodialysis due to chronic renal failure for eight yr was diagnosed with secondary hyperthyroidism and subsequently underwent total parathyroidectomy. The parathyroid cells were acquired from the resected tissues, processed through isolation and cultivation phases, and counted using a cell counter. A total of two million cells were injected into the left deltoid muscle using a 22-gauge needle. After surgery, five and 10 million cells were injected in the fifth and 12 week, respectively. The desired serum levels of parathyroid hormones and calcium were not achieved after the first two transplantations. In addition, there was no regression in the patient's symptoms. However, at four wk after the third transplantation, serum parathyroid hormone level did not decrease to <3 pg/mL, the patient was asymptomatic, and the oral treatment was stopped. Our findings indicate that this new technique is applicable because it is minimally invasive, and it can be easily repeated. PMID:25495657

Aysan, Erhan; Kilic, Ulkan; Gok, Ozlem; Altug, Burcugul; Ercan, Cilem; Idiz, Ufuk Oguz; Kesgin, Cemile; Muslumanoglu, Mahmut

2015-03-01

371

Vitamin D deficiency rickets in an adolescent with severe atopic dermatitis.  

PubMed

Atopic dermatitis (AD) affects 10% to 20% of children worldwide. Its severity may be inversely correlated with 25-hydroxyvitamin D (25OHD) levels. Although low levels of vitamin D (VD) can cause rickets in infants, VD deficiency rickets is an unusual presentation in teenagers. We report the case of a 14-year-old girl with severe AD and fish allergy since early childhood. She lived at high latitude (with less sun exposure) and, because of her atopic disorders, avoided sunlight and fish. Laboratory studies showed elevated alkaline phosphatase and parathyroid hormone levels and low serum calcium; her serum 25OHD level was <12 nmol/L. A radiograph of the wrist showed a radiolucent band in the distal metaphysis of the radius with marginal sclerosis. She was diagnosed as having hypocalcemic rickets due to VD deficiency. Treatment with VD increased her 25OHD level to 44 nmol/L, with normalization of alkaline phosphatase, parathyroid hormone, and calcium. Moreover, we observed a dramatic improvement in her AD severity with VD treatment. This case demonstrates the complex interaction between VD deficiency, AD, and food allergy. We advise a high index of suspicion of VD deficiency rickets in children of all ages with AD, particularly during accelerated growth periods and in the presence of other risk factors such as darker skin, living at high latitude, sun avoidance, and low intake of VD-rich foods. The concomitant improvement in bone-related parameters and AD severity may reflect a double benefit of VD treatment, a possibility that warrants research on VD as potential treatment for AD. PMID:24470638

Borzutzky, Arturo; Grob, Francisca; Camargo, Carlos A; Martinez-Aguayo, Alejandro

2014-02-01

372

VS-105: a novel vitamin D receptor modulator with cardiovascular protective effects  

PubMed Central

BACKGROUND AND PURPOSE Vitamin D receptor (VDR) modulators (VDRMs) such as calcitriol, paricalcitol and doxercalciferol are commonly used to manage hyperparathyroidism secondary to chronic kidney disease (CKD). CKD patients experience extremely high risks of cardiovascular morbidity and mortality. Clinical observations show that VDRM therapy may be associated with cardio-renal protective and survival benefits for CKD patients. However, hypercalcaemia remains a serious side effect for current VDRMs, which leads to the need for frequent dose titration and serum Ca (calcium) monitoring. Significant clinical benefits can be derived from a VDRM with cardiovascular protective effects without the hypercalcaemic liability. EXPERIMENTAL APPROACH Male Sprague–Dawley rats were 5/6 nephrectomized and 6 weeks later, after they had established uraemia, elevated parathyroid hormone levels, endothelial dysfunction and left ventricular hypertrophy, the rats were treated with VS-105, a novel VDRM. The effects of VS-105 were also tested in cultured HL-60 cells. KEY RESULTS VS-105 induced HL-60 cell differentiation with an EC50 value at 11.8 nM. Treatment (i.p., 3× a week over a period of 2 weeks) of the 5/6 nephrectomized rats by VS-105 (0.004–0.64 µg·kg?1) effectively suppressed serum parathyroid hormone without raising serum Ca or phosphate levels. Furthermore, 2 weeks of treatment with VS-105 improved endothelium-dependent aortic relaxation and attenuated left ventricular abnormalities in a dose range that did not affect serum Ca levels. Similar results were obtained when VS-105 was administered i.p. or by oral gavage. CONCLUSIONS AND IMPLICATIONS VS-105 exhibits an overall therapeutic product profile that supports expanded use in CKD to realize the cardiovascular protective effects of VDR activation. PMID:21557735

Wu-Wong, J Ruth; Kawai, Megumi; Chen, Yung-wu; Nakane, Masaki

2011-01-01

373

Vitamin B6  

MedlinePLUS

... only vitamin B6, or vitamin B6 with other B vitamins, are also available. Am I getting enough vitamin ... Heart disease Some scientists had thought that certain B vitamins (such as folic acid, vitamin B12, and vitamin ...

374

Rat parathyroid hormone (rPTH) ELISAs specific for regions (2-7), (22-34) and (40-60) of the rat PTH structure: influence of sex and age.  

PubMed

Rat (r) PTH ELISAs were used to study the influence of age and sex on rPTH levels and circulating PTH molecular forms separated by HPLC. Standard curves and saturation analysis were undertaken to define epitopes. Rats were sacrificed at approximately 27, 47 and 75days. Relevant biochemical parameters and 25(OH) vitamin D were measured. Differences between sexes were analyzed by Kruskal-Wallis ANOVA, followed by Dunn's test. Epitopes were localized in regions 2-7, 22-34 and 40-60 of rPTH structure for whole (W), total (T) and carboxyl (C) rPTH ELISAs. The W-rPTH assay only detected rPTH(1-84) and N-PTH in circulation while the T-PTH assay further detected large C-rPTH fragments. The C-rPTH assay detected all circulating rPTH molecular forms including smaller C-rPTH fragments. In both sexes, weight (p<0.001), ionized calcium, creatinine, albumin and 25(OH)D values (p<0.001) increased with age, while phosphate and alkaline phosphatase decreased (p<0.001). In male rats, W-rPTH remained unchanged, while T-rPTH rose slightly (p<0.05) and C-rPTH declined by half with time (p<0.001). In female rats, W-rPTH (p<0.05), T-rPTH (p<0.001) and C-rPTH (p<0.01) all increased in older animals. In both sexes, C-rPTH/W-rPTH and C-rPTH/T-rPTH ratios decreased between 25 and 47 days, to rise again between 47 and 75 days. The initial decrease may represent an adaptation to weaning and a change of diet between 25 and 47 days while the rise corresponds to higher calcium and 25(OH)D levels between 47 and 75 days. These changes were more pronounced in female rats, indicating an influence of sex on PTH molecular form secretion or metabolism. PMID:20627105

D'Amour, Pierre; Rousseau, Louise; Hornyak, Stephen; Yang, Zan; Cantor, Tom

2010-09-15

375

Vitamin D, light and mental health.  

PubMed

Vitamin D receptors and vitamin D metabolizing enzymes are present in the central nervous system. Calcitriol (the active vitamin D hormone) affects numerous neurotransmitters and neurotrophic factors, relevant for mental disorders. In the case of depressive disorders, considerable evidence supports a role of suboptimal vitamin D levels. However, the data are not conclusive and further studies are necessary. Especially, the relative importance of the pineal-melatonin system versus the vitamin D-endocrine system for the pathogenesis of seasonal affective disorders is presently unresolved. Two diagnoses, schizophrenia and autism, have been hypothetically linked to developmental (prenatal) vitamin D deficiency, however, also in adult patients, low levels have been reported, supporting the notion that vitamin D deficiency may not only be a predisposing developmental factor but also relate to the adult patients' psychiatric state. Two cases are described, whose psychiatric improvement coincided with effective treatment of vitamin D deficiency. PMID:20800506

Humble, Mats B

2010-11-01

376

Review: vitamin D, immunity and lupus.  

PubMed

The identification of vitamin D receptor in cells involved in the immune response and the discovery that activated dendritic cells produce vitamin D hormone suggested that vitamin D could exert immunoregulatory effects. Patients with autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus (SLE) show low 25-OH vitamin D serum levels. In particular, SLE patients have multiple risk factors for vitamin D deficiency and disease severity seems correlated with lower 25-OH vitamin D serum levels. Treatment of vitamin D deficiency could be particularly important in SLE patients due to concomitant insults on their tissues such as bone, and in view of the possible immunomodulatory effects exerted by vitamin D. PMID:18089676