Sample records for parathyroid hormone vitamin

  1. Parathyroid Hormone, Calcitonin, and Vitamin D

    NASA Technical Reports Server (NTRS)

    Potts, J. T.

    1972-01-01

    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.

  2. Vitamin D metabolites and bioactive parathyroid hormone levels during Spacelab 2

    NASA Technical Reports Server (NTRS)

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

    1988-01-01

    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.

  3. Parathyroid hormone decreases renal vitamin D receptor expression in vivo

    PubMed Central

    Healy, Kevin D.; Vanhooke, Janeen L.; Prahl, Jean M.; DeLuca, Hector F.

    2005-01-01

    The vitamin D receptor (VDR) is a nuclear transcription factor responsible for mediating the biological activities of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Renal and parathyroid gland VDR content is an important factor in calcium homeostasis, vitamin D metabolism, and the treatment of secondary hyperparathyroidism and renal osteodystrophy. In these tissues, VDR expression is highly regulated by the calcium and vitamin D status. Although 1,25(OH)2D3 up-regulates VDR expression, hypocalcemia and vitamin D deficiency result in drastically reduced expression of the receptor. The generation of 25-hydroxyvitamin D3-1?-hydroxylase-null mice, which are incapable of endogenously producing 1,25(OH)2D3, has allowed us to investigate the influence of parathyroid hormone (PTH) on VDR expression independent of PTH-mediated increases in 1,25(OH)2D3. Administration of human PTH (1-34) (110 ?g/kg per day) for 48 h reduced renal VDR levels from 515 to 435 fmol/mg protein (15%, P < 0.03) in wild-type mice. In the 25-hydroxyvitamin D3-1?-hydroxylase-null mice, PTH administration strongly reduced renal VDR levels, from 555 to 394 fmol/mg protein (29%, P < 0.001). These results demonstrate that PTH is a potent down-regulator of VDR expression in vivo. PMID:15769857

  4. Impact of Ergocalciferol Treatment of Vitamin D Deficiency on Serum Parathyroid Hormone Concentrations in Chronic Kidney Disease

    Microsoft Academic Search

    Anna L. Zisman; Marta Hristova; L. Tammy Ho; Stuart M. Sprague

    2007-01-01

    Background: Vitamin D deficiency is highly prevalent and associated with secondary hyperparathyroidism in patients with chronic kidney disease (CKD). The Kidney Disease Outcomes Quality Initiative (K\\/DOQI) guidelines recommend treatment of vitamin D deficiency starting with CKD stage 3, though no data are available showing an impact on serum parathyroid hormone (PTH) concentrations. The goal of this analysis, therefore, was to

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

    NASA Technical Reports Server (NTRS)

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

    1975-01-01

    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.

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

    PubMed Central

    Naveh-Many, T; Silver, J

    1990-01-01

    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

  7. Temporal Relationship between Vitamin D Status and Parathyroid Hormone in the United States

    PubMed Central

    Kroll, Martin H.; Bi, Caixia; Garber, Carl C.; Kaufman, Harvey W.; Liu, Dungang; Caston-Balderrama, Anne; Zhang, Ke; Clarke, Nigel; Xie, Minge; Reitz, Richard E.; Suffin, Stephen C.; Holick, Michael F.

    2015-01-01

    Background Interpretation of parathyroid hormone (iPTH) requires knowledge of vitamin D status that is influenced by season. Objective Characterize the temporal relationship between 25-hydroxyvitamin D3 levels [25(OH)D3] and intact iPTH for several seasons, by gender and latitude in the U.S. and relate 25-hydrovitamin D2 [25(OH)D2] levels with PTH levels and total 25(OH)D levels. Method We retrospectively determined population weekly-mean concentrations of unpaired [25(OH)D2 and 25(OH)D3] and iPTH using 3.8 million laboratory results of adults. The 25(OH)D3 and iPTH distributions were normalized and the means fit with a sinusoidal function for both gender and latitudes: North >40, Central 32–40 and South <32 degrees. We analyzed PTH and total 25(OH)D separately in samples with detectable 25(OH)D2 (?4 ng/mL). Findings Seasonal variation was observed for all genders and latitudes. 25(OH)D3 peaks occurred in September and troughs in March. iPTH levels showed an inverted pattern of peaks and troughs relative to 25(OH)D3, with a delay of 4 weeks. Vitamin D deficiency and insufficiency was common (33% <20 ng/mL; 60% <30 ng/mL) as was elevated iPTH levels (33%>65 pg/mL). The percentage of patients deficient in 25(OH)D3 seasonally varied from 21% to 48% and the percentage with elevated iPTH reciprocally varied from 28% to 38%. Patients with detectable 25(OH)D2 had higher PTH levels and 57% of the samples with a total 25(OH)D > 50 ng/mL had detectable 25(OH)D2. Interpretation 25(OH)D3 and iPTH levels vary in a sinusoidal pattern throughout the year, even in vitamin D2 treated patients; 25(OH)D3, being higher in the summer and lower in the winter months, with iPTH showing the reverse pattern. A large percentage of the tested population showed vitamin D deficiency and secondary hyperparathyroidism. These observations held across three latitudinal regions, both genders, multiple-years, and in the presence or absence of detectable 25(OH)D2, and thus are applicable for patient care. PMID:25738588

  8. 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...

  9. Aluminum, parathyroid hormone, and osteomalacia

    SciTech Connect

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

    1983-01-01

    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.

  10. Vitamin D and parathyroid hormone relationships with obesity, nitric oxide metabolites, oxidative stress, blood pressure, vascular function and salt sensitivity in African Americans

    Microsoft Academic Search

    Anna Liza B Valina-Toth

    2009-01-01

    African Americans relative to white have higher rates of hypertension, nitric oxide (NO)-mediated endothelial dysfunction, oxidative stress\\/inflammation, salt sensitivity and obesity. Moreover, vitamin D deficiency and reactive rises in parathyroid hormone (PTH) are highly prevalent in African Americans, particularly in those who are obese. Furthermore, depressed 25-hydroxyvitamin D (25-OH D) and elevated PTH levels have been linked to obesity, elevated

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

    PubMed Central

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

    2014-01-01

    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

  12. Relationships among Vitamin D Levels, Parathyroid Hormone, and Calcium Absorption in Young Adolescents

    PubMed Central

    Abrams, Steven A.; Griffin, Ian J.; Hawthorne, Keli M.; Gunn, Sheila K.; Gundberg, Caren M.; Carpenter, Thomas O.

    2005-01-01

    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 evaluate the relationships among vitamin D status, PTH, and calcium absorption in mid-pubertal boys and girls. Methods Calcium absorption was measured as part of an evaluation of the effects of prebiotics (inulin-type fructans) using a stable isotope method in 93 young adolescents, 12.7 ± 1.0 yr of age, receiving diets averaging approximately 900 mg/d calcium. Results A significant positive relation to calcium absorption was found for serum 1,25-dihydroxyvitamin D(P = 0.048) and PTH(P = 0.007), but not for 25-OHD (P = 0.77). PTH was significantly inversely related to 25-OHD and was positively related to serum 1,25-dihydroxyvitamin D and osteocalcin. PTH was marginally significantly inversely related to lumbar spinal, but not whole body, bone mineral density. Conclusions These data suggest that in adolescents, especially in the presence of vitamin D insufficiency, PTH secretion increases to adapt to higher rates of bone formation associated with growth. This results in higher serum 1,25(OH)2D concentrations and increased calcium absorption results. Vitamin D status, as reflected by the serum 25-OHD level, is not closely related to calcium absorption. Whether adaptation to low serum 25-OHD is adequate under physiologically stressful situations, including those leading to very low serum 25-OHD levels, is unknown. PMID:16076940

  13. 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

    Majid, Hafsa; Khan, Aysha Habib; Moatter, Tariq

    2015-01-01

    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. PMID:25695075

  14. Assay for parathyroid hormone receptors

    SciTech Connect

    Nissenson, R.A.; Teitelbaum, A.P.; Arnaud, C.D.

    1985-01-01

    The paper presents methods used to identify and quantify parathyroid hormone (PTH) receptors in kidney and bone. Experimental details are provided for the preparation of radioiodinated PTH, purification of labeled PTH, and PTH binding assays using renal plasma membranes and cultured cells from embryonic chick bone cells.

  15. Parathyroid hormone and bone biomechanics

    Microsoft Academic Search

    Matthew R. Allen; David B. Burr

    2006-01-01

    Parathyroid hormone (PTH) treatment, either in the form of teriparatide or recombinant human PTH(1–34), reduces the fracture\\u000a risk of osteoporotic women by enhancing both structural and material biomechanical properties. Cortical bone thickness and\\u000a cross-sectional moment of inertia increase because of new bone formation on periosteal and endocortical surfaces. Intracortical\\u000a porosity is increased yet preferential localization near the endocortical surface limits

  16. Parathyroid Hormone Levels and Cognition

    NASA Technical Reports Server (NTRS)

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

    2009-01-01

    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.

  17. Aspiration of enlarged parathyroid glands for parathyroid hormone assay

    SciTech Connect

    Doppmann, J.L. (National Inst. of Health, Bethesda, MD); Krudy, A.G.; Marx, S.J.

    1983-07-01

    Enlarged parathyroid glands were percutaneously aspirated under computed tomographic (CT) control in 7 patients, and levels of parathyroid hormone (PTH) and human thyroglobulin (HTg) were measured. All 7 patients had high levels of PtH in at least 1 specimen. It is concluded that the measurement of high concentrations of PTH in the aspirate from a cervical or mediastinal mass, with CT documentation of needle position, provides absolute localization of parathyroid masses.

  18. 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

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

    2015-04-01

    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

  19. [Parathyroid hormone and Wnt signaling].

    PubMed

    Tamura, Yukinori; Kaji, Hiroshi

    2013-06-01

    Parathyroid hormone (PTH) is clinically used as therapeutic agent for osteoporosis in Japan. However, the mechanisms for bone anabolic action of PTH are not fully understood. Recently, numerous studies suggest that PTH enhances bone formation through the suppression of sclerostin, DKK1 and sFRP1, inhibitors of Wnt-?-catenin signal. Moreover, we identified Tmem119 as new osteoblast differentiation factor, which is involved in an increase in?-catenin level by PTH in osteoblasts. Further understanding of Wnt-?-catenin signaling in the bone anabolic action by PTH may lead to the development of novel bone anabolic agent. PMID:23719497

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

    PubMed Central

    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

    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

  1. Parathyroid hormone levels predict posttotal thyroidectomy hypoparathyroidism.

    PubMed

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

    2014-08-01

    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

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

    PubMed

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

    2014-11-01

    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

  3. Determinants of Plasma Parathyroid Hormone Levels in Young Women

    Microsoft Academic Search

    Julie M. PaikGary; Gary C. Curhan; John P. Forman; Eric N. Taylor

    2010-01-01

    While the effects of calcium, phosphorus intake, and vitamin D on parathyroid hormone (PTH) have been well studied, less is\\u000a known about other factors that impact PTH. Our goal was to delineate associations between demographic, dietary, and plasma\\u000a factors and PTH. We conducted a cross-sectional study of intact PTH among 1,288 nonblack women in the Nurses Health Study\\u000a II aged

  4. Parathyroid hormone response to hypocalcemia in hemodialysis patients with osteomalacia

    Microsoft Academic Search

    Dennis Andress; Arnold J Felsenfeld; Anne Voigts; Francisco Llach

    1983-01-01

    Parathyroid hormone response to hypocalcemia in hemodialysis patients with osteomalacia. The parathyroid hormone response to hypocalcemia was investigated in hemodialysis patients with osteomalacia and compared to those with osteitis fibrosa. Hypocalcemia was induced during hemodialysis by employing a dialysate devoid of calcium. Patients with osteomalacia had a blunted maximum amino terminal parathyroid hormone response (± SD) (0.39 ± 0.33 vs.

  5. Role of 1,25-dihydroxyvitamin D on the skeletal resistance to parathyroid hormone

    Microsoft Academic Search

    Tilde Galceran; Kevin J Martin; Jeremiah J Morrissey; Eduardo Slatopolsky

    1987-01-01

    Role of 1,25-dihydroxy vitamin D on the skeletal resistance to parathyroid hormone. Hypocalcemia in chronic renal failure (CRF) has been attributed in part to a skeletal resistance (S.R.) to the calcemie action of parathyroid hormone (PTH) as a consequence of low levels of 1,25 (OH)2D3. To further elucidate the role of 1,25(OH)2D3 in the genesis of S.R., the calcemie effect

  6. Supplementation with 1000 IU vitamin D/d leads to parathyroid hormone suppression, but not increased fractional calcium absorption, in 4–8-y-old children: a double-blind randomized controlled trial1234

    PubMed Central

    Abrams, Steven A; Hawthorne, Keli M; Chen, Zhensheng

    2013-01-01

    Background: The effects of vitamin D supplementation in healthy prepubertal children on physiologic outcomes have not been investigated. Objective: The objective was to evaluate the effects of supplementation with 1000 IU vitamin D3/d on calcium absorption. Design: In a double-blind, placebo-controlled trial, we randomly assigned 64 children to 1000 IU vitamin D3/d (n = 32) or placebo (n = 32) for 8 wk. Stable isotopes were used to assess calcium absorption. The main outcome measure was calcium absorption before and after supplementation. Results: All of the data are shown as means ± SDs. At baseline, vitamin D intake was 221 ± 79 IU/d and calcium intake was 830 ± 197 mg/d. Baseline serum 25-hydroxyvitamin D [25(OH)D] was not significantly correlated with fractional or total calcium absorption. After 8 wk, with baseline values used as a covariate, no differences were seen in fractional or total calcium absorption based on supplementation group (P = 0.75 and 0.36, respectively). Supplemented children had a significant increase in 25(OH)D concentrations (from 27.7 ± 7.4 to 36.0 ± 10.3 ng/mL; P < 0.0001) and a decrease in parathyroid hormone (from 21.4 ± 10.4 to 12.9 ± 7.1 pg/mL; P < 0.001); no significant changes in the placebo group were observed. No adverse side effects were noted in either group. Conclusions: Vitamin D3 supplementation at 1000 IU/d increases 25(OH)D and decreases parathyroid hormone in children with average vitamin D intakes below the dietary recommendations of the Institute of Medicine. However, no significant effects of this change on calcium absorption occurred. This trial was registered at clinicaltrials.gov as NCT 00868738. PMID:23151536

  7. Parathyroid hormone and left ventricular hypertrophy

    Microsoft Academic Search

    F. N. Saleh; H. Schirmer; J. Sundsfjord; R. Jorde

    2003-01-01

    Aims A relation between left ventricular hypertrophy and parathyroid hormone (PTH) has been described in patients with end stage renal disease and secondary hyperpar- athyroidism. In vitro studies indicate a hypertrophic effect of PTH on cardiomyocytes. The purpose of this study was to examine the relation between PTH and left ventricular hypertrophy in a general population. Methods and results The

  8. Parathyroid hormone binding to cultured avian osteoclasts

    SciTech Connect

    Teti, A.; Rizzoli, R.; Zambonin Zallone, A. (Univ. of Bari (Italy))

    1991-02-14

    Parathyroid hormone (PTH) increases serum calcium concentration via a controversial cellular mechanism. We investigated whether PTH binds avian osteoclasts. Isolated hypocalcaemic hen osteoclasts were incubated with ({sup 125}I)--bovine PTH (1-84). Specific binding of the hormone to the cells, which reached the equilibrium within 60 min, was observed. Half maximal binding was reached by 10 min. Binding was competitively inhibited by increasing doses of unlabeled PTH, and was about 55% displaced by adding, at the equilibrium, 10(-6) M unlabeled PTH. Autoradiography demonstrated specific label on the osteoclast. The cellular mechanism activated by the hormone remains to be elucidated.

  9. 21 CFR 862.1545 - Parathyroid hormone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1545 Parathyroid hormone test system. (a)...

  10. 21 CFR 862.1545 - Parathyroid hormone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1545 Parathyroid hormone test system. (a)...

  11. 21 CFR 862.1545 - Parathyroid hormone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1545 Parathyroid hormone test system. (a)...

  12. 21 CFR 862.1545 - Parathyroid hormone test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1545 Parathyroid hormone test system. (a)...

  13. Sequences of the cDNAs encoding canine parathyroid hormone-related protein and parathyroid hormone

    Microsoft Academic Search

    T. J. Rosol; C. L. Steinmeyer; L. K. McCauley; A. Gröne; J. W. Dewille; C. C. Capen

    1995-01-01

    The cDNA clones encoding canine parathyroid-hormone-related protein (cPTHrP) and parathyroid hormone (cPTH) have been isolated and sequenced. The predicted amino-acid sequences of the mature canine homologs have a high degree of homology to human PTHrP (hPTHrP) and PTH (hPTH), especially in the biologically active regions. The cPTHrP cDNA is unique, since it has homology to exon lA of hPTHrP which

  14. Effects of a Short-Term Vitamin D3 and Calcium Supplementation on Blood Pressure and Parathyroid Hormone Levels in Elderly Women

    Microsoft Academic Search

    MICHAEL PFEIFER; BETTINA BEGEROW; HELMUT W. MINNE; DETLEF NACHTIGALL; CORINNA HANSEN

    2010-01-01

    Calcium supplementation is effective in reducing blood pressure in various states of hypertension, including pregnancy-induced hyperten- sion and preeclampsia. In addition, calcitropic hormones are associated with blood pressure. The hypothesis is that short-term therapy with calcium and vitamin D3 may improve blood pressure as well as secondary hyperparathyroidism more effectively than calcium monotherapy. The effects of 8 weeks of supplementation

  15. Predictive value of serum parathyroid hormone levels for bone turnover in patients on chronic maintenance dialysis

    Microsoft Academic Search

    Quanle Qi; Marie-Claude Monier-Faugere; Zhaopo Geng; Hartmut H. Malluche

    1995-01-01

    With the increasing occurrence of adynamic bone disease, it is essential to determine the level of bone turnover in chronically dialyzed patients before instituting vitamin D therapy. To assess the value of serum parathyroid hormone (PTH) levels for prediction of bone turnover, we determined sensitivity, specificity, and predictive value positive of serum PTH, alone or in combination with other variables,

  16. Annotation: Parathyroid hormone and fracture healing

    PubMed Central

    2013-01-01

    This annotation describes some early rat studies which conclude that parathyroid hormone (PTH) has more dramatic stimulatory effects on bone repair than on untraumatized bone. It also suggests, based on the effects of PTH on osteoblasts, that it is more likely to accelerate normal fracture healing than to prevent non-union. The only 2 controlled clinical trials that have been published are critically discussed. Although both are encouraging and appear to show acceleration of normal fracture healing, they have methodological shortcomings that preclude definitive conclusions. PMID:23368745

  17. Annotation: parathyroid hormone and fracture healing.

    PubMed

    Aspenberg, Per

    2013-02-01

    This annotation describes some early rat studies which conclude that parathyroid hormone (PTH) has more dramatic stimulatory effects on bone repair than on untraumatized bone. It also suggests, based on the effects of PTH on osteoblasts, that it is more likely to accelerate normal fracture healing than to prevent non-union. The only 2 controlled clinical trials that have been published are critically discussed. Although both are encouraging and appear to show acceleration of normal fracture healing, they have methodological shortcomings that preclude definitive conclusions. PMID:23368745

  18. Associations Between Serum-Intact Parathyroid Hormone, Serum 25-Hydroxyvitamin D, Oral Vitamin D Analogs and Metabolic Syndrome in Peritoneal Dialysis Patients: A Multi-Center Cross-Sectional Study

    PubMed Central

    Dong, Jie; Wang, Qin; Chen, Meng-Hua; Zhao, Hui-Ping; Zhu, Tong-Ying; Tian, Na; Wang, Mei; Hao, Chuan-Ming; Ren, Ye-Ping; Wang, Hai-Yan

    2014-01-01

    ? Introduction: Although previous studies have suggested associations between serum intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25(OH)D) and metabolic syndrome (MS) in the general population, these associations are still uncharacterized in peritoneal dialysis (PD) patients. ? Methods: In total, 837 prevalent PD patients from 5 centers in China were enrolled between April 1, 2011 and November 1, 2011. The demographic data, biochemical parameters and medical records were collected, except for serum 25(OH)D which was measured in 347 of 837 patients. The definition of MS was modified from National Cholesterol Education Program Third Adult Treatment Panel (NCEP-ATPIII). ? Results: 55.4% of 837 patients were found to have MS. The median concentration of iPTH, 25(OH)D and doses of oral vitamin D analogs for participants with MS was significantly lower than those without MS. The iPTH, 25(OH)D values and doses of vitamin D analogs were all associated with one or more components of MS. After multivariate adjustment, low serum iPTH values and oral vitamin D analogs, rather than serum 25(OH)D, were significantly associated with the presence of MS, abnormal fasting blood glucose (FBG) and high-density lipoprotein cholesterol (HDL-C). Compared to iPTH < 130pg/mL, iPTH 130-585 pg/mL and > 585pg/mL were associated with a lower risk of MS with adjusted odds ratio (OR) of 0.59 and 0.33, respectively. Taking vitamin D analogs was also associated with a lower risk of MS with adjusted OR of 0.55. ? Conclusions: Serum iPTH and the use of active vitamin D supplements rather than serum 25(OH)D were independently associated with the presence of MS in patients on PD. PMID:24497582

  19. Immunoprecipitation of the parathyroid hormone receptor

    SciTech Connect

    Wright, B.S.; Tyler, G.A.; O'Brien, R.; Caporale, L.H.; Rosenblatt, M.

    1987-01-01

    An /sup 125/I-labeled synthetic analog of bovine parathyroid hormone, (8-norleucine,18-norleucine,34-tyrosine)PTH-(1-34) amide ((Nle)PTH-(1-34)-NH/sub 2/), purified by high-pressure liquid chromatography (HPLC), was employed to label the parathyroid hormone (PTH) receptor in cell lines derived from PTH target tissues: the ROS 17/2.8 rat osteosarcoma of bone and the CV1 and COS monkey kidney lines. After incubation of the radioligand with intact cultured cells, the hormone was covalently attached to receptors by using either a photoaffinity technique or chemical (affinity) crosslinking. In each case, covalent labeling was specific, as evidenced by a reduction of labeling when excess competing nonradioactive ligand was present. After covalent attachment of radioligand, membranes were prepared form the cells and solubilized in the nonionic detergent Nonidet P-40 or octyl glucoside. Analysis of the immunoprecipitate on NaDod-SO/sub 4//polyacrylamide gel electrophoresis followed by autoradiography revealed the presence of a doublet of apparent molecular mass 69-70 kDa. Specifically labeled bands of approximate molecular mass 95 and 28 kDa were also observed. The anti-PTH IgG was affinity purified by passage over a PTH-Sepharose column and used to made an immunoaffinity column. These studies suggest that the use of an anti-PTH antiserum that binds receptor-bound hormone is likely to be a useful step in the further physicochemical characterization and purification of the PTH receptor.

  20. 1,25(OH)2 vitamin D3 inhibits parathyroid cell proliferation in experimental uremia

    Microsoft Academic Search

    Andras Szabo; Jürgen Merke; Eric Beier; Gerhard Mall; Eberhard Ritz

    1989-01-01

    1,25(OH)2 vitamin D3 inhibits parathyroid cell proliferation in experimental uremia. Parathyroid cell proliferation and parathyroid hyperplasia are features of renal secondary hyperparathyroidism. Since parathyroids have recently been recognized as an important target for 1,25(OH)2D3, the effects of administration of variable doses of 1,25(OH)2D3 on ex vivo radiothymidine incorporation in the parathyroid glands, on parathyroid cell mitoses, on parathyroid weight, morphometric

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

    PubMed Central

    Kimura, Shigemi; Yoshioka, Kowasi

    2014-01-01

    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

  2. Intraoperative Parathyroid Hormone Analysis: A Study of 200 Consecutive Cases

    Microsoft Academic Search

    Lori J. Sokoll; Helen Drew; Robert Udelsman

    Background: Immunoassays for parathyroid hormone (PTH), with short incubation times and results available in <15 min, have allowed intraoperative monitoring of the success of parathyroid surgery. The purpose of this study was to evaluate the analytical performance of a rapid PTH assay and its clinical performance in a series of 200 patients. Methods: PTH was measured with a modified immuno-

  3. The Case for Routine Parathyroid Hormone Monitoring

    PubMed Central

    Moe, Sharon M.

    2013-01-01

    Summary Parathyroid hormone (PTH) is a uremic toxin with multiple systemic effects including bone disorders (renal osteodystrophy), myopathy, neurologic abnormalities, anemia, pruritus, and cardiomyopathy. Hyperparathyroidism is common in CKD and results in significant morbidity and mortality if left untreated. Clinical practice guidelines from the Kidney Disease Improving Global Outcomes initiative broadened the optimal PTH range to >2 and <9 times the upper limit of normal for the assay measured. Furthermore, the guidelines recommend following trends in PTH to determine the appropriate therapy. These guidelines overcome issues with the assay variability and help clinicians make judgments when treating individual patients. They also require frequent measurement in order to determine trends and implement appropriate treatments. PMID:23037984

  4. Parathyroid carcinoma: location of pelvic metastases by parathyroid hormone assay

    PubMed Central

    Murray, Timothy M.; Patt, Norman L.; Muzaffar, Syed Ali

    1974-01-01

    A metastasis from a functioning parathyroid carcinoma was located by PTH radioimmunoassay and selective venous catheterization. The site of the metastasis, verified at autopsy, was in the right side of the pelvis. This is the most distant reported location for metastatic parathyroid carcinoma. The patient's plasma immunoreactive PTH rose more than twofold in response to induced hypocalcemia. This suggests that relative hypocalcemia, induced therapeutically in such patients, may result in a higher chronic level of PTH secretion. ImagesFIG. 3 PMID:4363399

  5. Effects of Parathyroid Hormone on Bone of Thyroparathyroidectomized Rats

    PubMed Central

    Weisbrode, Steven E.; Capen, Charles C.; Nagode, Larry A.

    1974-01-01

    Osteoblasts and osteocytes in adult thyroparathyroidectomized (TxPTx) rats fed a low calcium vitamin D-free diet and given parathyroid (PTH) had ultrastructural evidence of increased activity compared to controls. Osteoblasts in PTH-treated rats had prominent rough endoplasmic reticulum and Golgi apparatuses and large mitochondria. The plasma membranes were extensively convoluted and associated with initial loci of mineralization in osteoid. Osteocytes contained increased rough endoplasmic reticulum, well-developed Golgi apparatuses and large mitochondria. Lacunar walls were roughened, but osteocytic osteolysis was not observed. Osteoclasts were encountered more frequently in PTH-treated rats, but their ultrastructural features were similar to those of controls. Osteoblasts and osteocytes in controls appeared to be inactive cells lining quiescent mineral surfaces. Parathyroid hormone treatment increased serum calcium levels and urinary hydroxyproline excretion, indicating enhanced resorption of bone mineral and matrix. Bone alkaline phosphatase and calcium-adenosine triphosphatase activities were elevated after PTH treatment and may be related to increased calcium transport by bone cells. These findings were interpreted to suggest that PTH mobilizes bone mineral by osteoclasis and increases metabolic activity of the osteocyte-osteoblast pump. ImagesFig 11Fig 1Fig 2Fig 3Fig 4Fig 5Fig 6Fig 7Fig 8Fig 9Fig 10 PMID:4275712

  6. Effect of parathyroid hormone on energy metabolism of skeletal muscle

    Microsoft Academic Search

    Ryszard Baczynski; Shaul G Massry; Maria Magott; Sami El-Belbessi; Ricardo Kohan; Nachman Brautbar; G Massry

    1985-01-01

    Effect of parathyroid hormone on energy metabolism of skeletal muscle. Clinical states with primary or secondary hyperparathyroidism are associated with muscle dysfunction, suggesting that parathyroid hormone (PTH) may affect muscle metabolism. The present study examined the effect of 1–84 PTH and its amino-terminal fragment (1–34 PTH) on energy production, transfer, and utilization by skeletal muscle. Rats weighing 150 to 200

  7. Therapy of Hypoparathyroidism by Replacement with Parathyroid Hormone

    PubMed Central

    2014-01-01

    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

  8. Degradation of parathyroid hormone in macrophage endosomes

    SciTech Connect

    Diment, S.; Martin, K.J.; Stahl, P.D.

    1986-05-01

    Parathyroid hormone (PTH) is secreted as an 84 amino acid protein that is rapidly cleaved between amino acids 34 and 35 by Kupffer cells in liver. The resulting amino terminal peptide (1-34) is active at PTH target organs (kidney and bone). Cathepsin D can process PTH to 1-34 in vitro, and a cathepsin D-like protease, which may rapidly process proteins, is present in endosomes of alveolar macrophages. The authors set out to determine whether PTH is degraded to 1-34 in endosomes, and to elucidate the mechanism of hormone processing in vivo. Intracellular transport of /sup 125/I-PTH was assessed by binding to alveolar macrophages at 4/sup 0/C, followed by internalization at 37/sup 0/C. Distribution of PTH among plasma membranes, endosomes and lysosomes was determined by subcellular fractionation. Degradation of the ligand to TCA-soluble fragments in each compartment was assayed at neutral and acid pH. 1-34 in supernatants was separated from undergraded PTH by gel filtration and detected by bioassay on kidney membranes. The authors data suggest that: 1) macrophages rapidly degrade PTH to TCA-soluble fragments. 2) macrophages do not secrete proteases that degrade extracellular PTH. 3) PTH is internalized into endocytic vesicles after 5 mins, but not delivered to lysosomes within 30 mins. 4) A bioactive peptide is released into the extracellular medium after 20 mins. 5) PTH is degraded in endosomes at acid pH by a pepstatin-sensitive protease.

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

    SciTech Connect

    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

    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.

  10. Vitamin D: a pleiotropic hormone

    Microsoft Academic Search

    Annemieke Verstuyf; Geert Carmeliet; Roger Bouillon; Chantal Mathieu

    2010-01-01

    The secosteroid hormone 1?,25-dihydroxyvitamin D3 (1,25(OH)2D3) 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

  11. Sarcoidosis-related hypercalcaemia due to production of parathyroid hormone-related peptide.

    PubMed

    Raalte, Daniel H van; Goorden, Susan M; Kemper, Evelien A; Brosens, Lodewijk A A; Ten Kate, Reinier W

    2015-01-01

    Hypercalcaemia is frequently observed in patients with sarcoidosis. This is classically attributed to ectopic production of 1,25 dihydroxy vitamin D by sarcoid granulomas. We present a case of sarcoidosis-related hypercalcaemia with normal vitamin D levels. In this patient, production of parathyroid hormone-related peptide (PTHrp) was the cause for sarcoidosis-induced hypercalcaemia. As such, plasma PTHrp levels were increased and bone marrow granulomas stained positively for PTHrp expression. Medium-dose prednisolone treatment improved symptoms of sarcoidosis and normalised serum calcium, and PTHrp concentrations. Thus, production of PTHrp may be the cause for hypercalcaemia in some patients with sarcoidosis. PMID:26160550

  12. Use of parathyroid hormone in hypoparathyroidism

    PubMed Central

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

    2015-01-01

    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

  13. Parathyroid Hormone and Physical Exercise: a Brief Review

    PubMed Central

    Bouassida, Anissa; Latiri, Imed; Bouassida, Semi; Zalleg, Dalenda; Zaouali, Monia; Feki, Youssef; Gharbi, Najoua; Zbidi, Abdelkarim; Tabka, Zouhair

    2006-01-01

    Parathyroid hormone (PTH) is the major hormone regulating calcium metabolism and is involved in both catabolic and anabolic actions on bone. Intermittent PTH exposure can stimulate bone formation and bone mass when PTH has been injected. In contrast, continuous infusion of PTH stimulates bone resorption. PTH concentration may be affected by physical exercise and our review was designed to investigate this relationship. The variation in PTH concentration appears to be influenced by both exercise duration and intensity. There probably exists a stimulation threshold of exercise to alter PTH. PTH regulation is also influenced by the initial bone mineral content, age, gender, training state, and other hormonal and metabolic factors (catecholamines, lactic acid and calcium concentrations). Key Points Physical exercise can improve PTH secretion. Parathyroid hormone has both anabolic and catabolic effects on bone: intermittent treatment of PTH is anabolic whereas continuous treatment is catabolic. PMID:24353453

  14. New Members of the Parathyroid Hormone\\/Parathyroid Hormone Receptor Family: The Parathyroid Hormone 2 Receptor and Tuberoinfundibular Peptide of 39 Residues

    Microsoft Academic Search

    Ted B. Usdin; Tianlun Wang; Samuel R. J. Hoare; Éva Mezey; Miklós Palkovits

    2000-01-01

    The parathyroid hormone (PTH) family currently includes three peptides and three receptors. PTH regulates calcium homeostasis through bone and kidney PTH1 receptors. PTH-related peptide, probably also through PTH1 receptors, regulates skeletal, pancreatic, epidermal, and mammary gland differentiation and bladder and vascular smooth muscle relaxation and has a CNS role that is under investigation. Tuberoinfundibular peptide of 39 residues (TIP39) was

  15. Parathyroid hormone, but not vitamin D, is associated with the metabolic syndrome in morbidly obese women and men: a cross-sectional study

    PubMed Central

    Hjelmesćth, Jřran; Hofsř, Dag; Aasheim, Erlend T; Jenssen, Trond; Moan, Johan; Hager, Helle; Rřislien, Jo; Bollerslev, Jens

    2009-01-01

    Background The prevalence of vitamin D insufficiency and secondary hyperparathyroidism is high among morbidly obese subjects. Further, low serum levels of 25-hydroxyvitamin D (25 [OH]D) and magnesium have been associated with increased risk of the metabolic syndrome (MS), and recently, a possible link between PTH and MS has been reported. Although it is well known that the synthesis and secretion of PTH is regulated by serum levels of calcium, phosphate, magnesium and 25(OH)D, less is known about the possible clustered affiliation of these parameters with MS. We aimed to explore whether MS is associated with abnormal serum levels of PTH, 25(OH)D and magnesium in a population of morbidly obese patients. Methods Fasting serum levels of 25(OH)D, PTH and magnesium were assessed in a cross-sectional cohort study of 1,017 consecutive morbidly obese patients (68% women). Multiple logistic regression analyses were used to assess the independent effect of PTH, 25(OH)D and magnesium on the odds for MS (National Cholesterol Education Program [NCEP]) after adjustment for confounding factors. Results Sixty-eight percent of the patients had MS. Patients with MS had lower mean serum magnesium (P < 0.001) and higher mean PTH (P = 0.067) than patients without MS, whereas mean 25(OH)D did not differ significantly. Patients with PTH levels in the second to fourth quartiles had higher odds of prevalent MS (odds ratio 1.47 [95% CI 0.92–2.35], 2.33 [95% CI 1.40–3.87] and 2.09 [95% CI 1.23–3.56], respectively), after adjustment for 25(OH)D, magnesium, calcium, phosphate, creatinine, age, gender, season of serum sampling, BMI, current smoking, albuminuria, CRP, insulin resistance and type 2 diabetes. Further, PTH was significantly correlated with systolic and diastolic pressure (both P < 0.001), but not with the other components of MS. The levels of 25(OH)D and magnesium were not associated with MS in the multivariate model. Conclusion The PTH level, but not the vitamin D level, is an independent predictor of MS in treatment seeking morbidly obese Caucasian women and men. Randomized controlled clinical trials, including different therapeutic strategies to lower PTH, e.g. calcium/vitamin D supplementation and weight reduction, are necessary to explore any cause-and-effect relationship. PMID:19187564

  16. 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

    2012-01-01

    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

  17. Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats.

    PubMed

    Gowen, M; Stroup, G B; Dodds, R A; James, I E; Votta, B J; Smith, B R; Bhatnagar, P K; Lago, A M; Callahan, J F; DelMar, E G; Miller, M A; Nemeth, E F; Fox, J

    2000-06-01

    Parathyroid hormone (PTH) is an effective bone anabolic agent, but it must be administered parenterally. An orally active anabolic agent would provide a valuable alternative for treating osteoporosis. NPS 2143 is a novel, selective antagonist (a "calcilytic") of the parathyroid cell Ca(2+) receptor. Daily oral administration of NPS 2143 to osteopenic ovariectomized (OVX) rats caused a sustained increase in plasma PTH levels, provoking a dramatic increase in bone turnover but no net change in bone mineral density. Concurrent oral administration of NPS 2143 and subcutaneous infusion of 17beta-estradiol also resulted in increased bone turnover. However, the antiresorptive action of estrogen decreased the extent of bone resorption stimulated by the elevated PTH levels, leading to an increase in bone mass compared with OVX controls or to either treatment alone. Despite the sustained stimulation to the parathyroid gland, parathyroid cells did not undergo hyperplasia. These data demonstrate that an increase in endogenous PTH secretion, induced by antagonism of the parathyroid cell Ca(2+) receptor with a small molecule, leads to a dramatic increase in bone turnover, and they suggest a novel approach to the treatment of osteoporosis. PMID:10841518

  18. Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats

    PubMed Central

    Gowen, Maxine; Stroup, George B.; Dodds, Robert A.; James, Ian E.; Votta, Bart J.; Smith, Brian R.; Bhatnagar, Pradip K.; Lago, Amparo M.; Callahan, James F.; DelMar, Eric G.; Miller, Michael A.; Nemeth, Edward F.; Fox, John

    2000-01-01

    Parathyroid hormone (PTH) is an effective bone anabolic agent, but it must be administered parenterally. An orally active anabolic agent would provide a valuable alternative for treating osteoporosis. NPS 2143 is a novel, selective antagonist (a “calcilytic”) of the parathyroid cell Ca2+ receptor. Daily oral administration of NPS 2143 to osteopenic ovariectomized (OVX) rats caused a sustained increase in plasma PTH levels, provoking a dramatic increase in bone turnover but no net change in bone mineral density. Concurrent oral administration of NPS 2143 and subcutaneous infusion of 17?-estradiol also resulted in increased bone turnover. However, the antiresorptive action of estrogen decreased the extent of bone resorption stimulated by the elevated PTH levels, leading to an increase in bone mass compared with OVX controls or to either treatment alone. Despite the sustained stimulation to the parathyroid gland, parathyroid cells did not undergo hyperplasia. These data demonstrate that an increase in endogenous PTH secretion, induced by antagonism of the parathyroid cell Ca2+ receptor with a small molecule, leads to a dramatic increase in bone turnover, and they suggest a novel approach to the treatment of osteoporosis. PMID:10841518

  19. Parathyroid hormone and growth in chronic kidney disease

    Microsoft Academic Search

    Simon Waller

    2011-01-01

    Growth failure is common in children with chronic kidney disease, and successful treatment is a major challenge in the management\\u000a of these children. The aetiology is multi-factorial with “chronic kidney disease–metabolic bone disorder” being a key component\\u000a that is particularly difficult to manage. Parathyroid hormone is at the centre of this mineral imbalance, consequent skeletal\\u000a disease and, ultimately, growth failure.

  20. Parathyroid hormone-related protein and lung biology

    Microsoft Academic Search

    Randolph H. Hastings

    2004-01-01

    Parathyroid hormone-related protein (PTHrP) is expressed in normal and malignant lung and has roles in development, homeostasis, and pathophysiology of injury and cancer. Its effects in developing lung include regulation of branching morphogenesis and type II cell maturation. In adult lung, PTHrP stimulates disaturated phosphatidylcholine secretion, inhibits type II cell growth, and sensitizes them to apoptosis. In lung cancer, PTHrP

  1. Spatial and Temporal Expression of Parathyroid Hormone-Related Protein during Wound Healing

    Microsoft Academic Search

    Eric A. G. Blomme; Hong Zhou; Vicky Kartsogiannis; Charles C. Capen; Thomas J. Rosol

    1999-01-01

    Parathyroid hormone-related protein is produced by many normal tissues including the skin, where it regulates growth and differentiation of keratinocytes. To define better the role of parathyroid hormone-related protein in the skin, we investigated the spatial and temporal expression of parathyroid hormone-related protein and mRNA by immunohistochemistry and in situ hybridization during the healing of skin wounds, and the effects

  2. Parathyroid biopsy

    MedlinePLUS

    ... under a microscope. The level of parathyroid hormone (PTH) in your blood will also be checked. ... The parathyroid glands release parathyroid hormone (PTH). This ... body. This procedure is most often done to rule out cancer as a ...

  3. Interspecies comparison of renal cortical receptors for parathyroid hormone and parathyroid hormone-related protein

    SciTech Connect

    Orloff, J.J.; Goumas, D.; Wu, T.L.; Stewart, A.F. (West Haven Veterans Administration Medical Center, CT (USA))

    1991-03-01

    Parathyroid hormone (PTH) and PTH-related proteins (PTHrP) interact with a common receptor in rat bone cells and in canine renal membranes with similar affinity, but PTHrP are substantially less potent than PTH in stimulating adenylate cyclase in canine renal membranes; in contrast, PTH and PTHrP are equipotent in stimulating adenylate cyclase in rat bone cells. This discrepancy has been largely viewed as reflecting differences in the relative efficiency of signal transduction of PTHrP between bone and kidney assay systems. To test the alternative (but not mutually exclusive) hypothesis that these differences could reflect interspecies differences in PTH receptors, we have characterized the bioactivity of amino-terminal PTHrP and PTH in rat and human renal cortical membranes (RCM) and compared them to results we previously reported in canine RCM. The stability of PTH and PTHrP peptides under binding and adenylate cyclase assay conditions was greater than 80% for each species. Competitive inhibition of ({sup 125}I)(Tyr36)hPTHrP-(1-36)NH{sub 2} binding to rat RCM by bPTH-(1-34) and (Tyr36)hPTHrP-(1-36)NH{sub 2} yielded nearly identical binding dissociation constants (3.7 and 3.6 nM, respectively), and binding to human RCM demonstrated slightly greater potency for PTHrP (0.5 nM) than for PTH (0.9 nM). Similarly, adenylate cyclase stimulating activity was equivalent for the two peptides in rat RCM, but PTHrP was twofold more potent than PTH in human RCM. Covalent photoaffinity labeling of protease-protected rat RCM yielded an apparent 80 kD receptor protein, and cross-linking of human RCM labeled an 85 kD receptor, indistinguishable in size from the canine renal PTH receptor. We conclude that rat, canine, and human renal cortical PTH receptors exhibit species specificity.

  4. Three-phase model harmonizes estimates of the maximal suppression of parathyroid hormone by 25-hydroxyvitamin D in persons 65 y of age and older

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The concentration or threshold of 25-Hydroxyvitamin D [25(OH)D] needed to maximally suppress intact serum parathyroid hormone (iPTH) has been suggested as a measure of optimal vitamin D status. Depending upon the definition of maximal suppression of iPTH and the two-phase regression approach used, ...

  5. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis

    Microsoft Academic Search

    Dennis M. Black; Susan L. Greenspan; Kristine E. Ensrud; Lisa Palermo; Joan A. McGowan; Thomas F. Lang; Patrick Garnero; Mary L. Bouxsein; John P. Bilezikian; Clifford J. Rosen

    2003-01-01

    BACKGROUND: Parathyroid hormone increases bone strength primarily by stimulating bone formation, whereas antiresorptive drugs reduce bone resorption. We conducted a randomized, double-blind clinical study of parathyroid hormone and alendronate to test the hypothesis that the concurrent administration of the two agents would increase bone density more than the use of either one alone. METHODS: A total of 238 postmenopausal women

  6. Ultrasonographic evaluation of parathyroid hyperplasia in multiple endocrine neoplasia type 1: Positive correlation between parathyroid volume and circulating parathyroid hormone concentration.

    PubMed

    Tamiya, Hiroyuki; Miyakawa, Megumi; Takeshita, Akira; Miura, Daishu; Takeuchi, Yasuhiro

    2014-09-17

    There are few reports on parathyroid ultrasonography of multiple endocrine neoplasia type 1 (MEN1). This study investigated the ultrasonographic features of parathyroid glands in 10 patients with MEN1 who underwent preoperative neck ultrasonography and parathyroidectomy between 2006 and 2010 at Toranomon Hospital. We retrospectively analyzed clinical features, laboratory and ultrasonographic data, and pathological diagnosis. A total of 38 parathyroid glands were surgically removed (three to five glands from each patient). All removed parathyroids were pathologically diagnosed as hyperplasia. Seven cases (70.0 %) had adenomatous thyroid nodules. Twenty-five enlarged parathyroid glands (65.8 %) were detected by preoperative ultrasonography with a detection rate of 81.8 % (9/11) and 59.3 % (16/27) for patients without and with adenomatous nodules, respectively. Total parathyroid gland weight and potentially predictable total parathyroid volume by preoperative ultrasonography were significantly correlated with preoperative serum intact parathyroid hormone (iPTH) concentration (R = 0.97, P < 0.001 and R = 0.96, P < 0.001, respectively). The equation used for prediction of the total volume by ultrasonography was 15 × iPTH (pg/ml) - 1,000 and that for total weight was 20 × iPTH (pg/ml) - 1,400. Although adenomatous nodules often coexisted with MEN1 and made identification of enlarged parathyroid glands by ultrasonography difficult, the positive correlation between the predictable parathyroid volume by ultrasonography and serum iPTH suggests that their measurement is useful in the preoperative detection and localization of enlarged parathyroid glands in patients with MEN1. Furthermore, the presence of parathyroid glands that should be resected can be predicted before surgery using the equation proposed here. PMID:25227285

  7. Pseudohypoparathyroidism: defective excretion of 3?,5?-AMP in response to parathyroid hormone

    PubMed Central

    Chase, Lewis R.; Melson, G. Leland; Aurbach, G. D.

    1969-01-01

    Urinary excretion of cyclic adenosine 3?,5?-monophosphate (3?,5?-AMP) was tested in normal subjects and patients with pseudohypoparathyroidism, idiopathic hypoparathyroidism, surgical hypoparathyroidism, and pseudopseudohypoparathyroidism under basal conditions and after a 15 min infusion of purified parathyroid hormone. Basal excretion of the nucleotide was less than normal in the patients with hypocalcemic disorders and greater than normal in pseudopseudohypoparathyroidism. Parathyroid hormone caused a marked increase in excretion of 3?,5?-AMP in all subjects except those with pseudohypoparathyroidism; nine patients with this disorder did not respond to the hormone and four showed a markedly deficient response. Radioimmunoassay showed that parathyroid hormone circulated in increased amounts in plasma from patients with pseudohypoparathyroidism and became undetectable when serum calcium was increased above 12 mg/100 ml. Suppression of parathyroid hormone secretion by induction of hypercalcemia did not alter the deficient response to exogenous hormone. The results indicate that: (a) parathyroid hormone circulates in abnormally high concentrations in pseudohypoparathyroidism and secretion of the hormone responds normally to physiological control by calcium; (b) testing urinary excretion of 3?,5?-AMP in response to infusion of purified parathyroid hormone appears to be an accurate and sensitive index for establishing the diagnosis of pseudohypoparathyroidism; and (c) the metabolic defect of the disorder can be accounted for by a lack of or defective form of parathyroid hormone-sensitive adenyl cyclase in bone and kidney. PMID:4309802

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

    PubMed

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

    2015-02-01

    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

  9. Current concepts of the metabolism and radioimmunoassay of parathyroid hormone

    SciTech Connect

    Slatopolsky, E.; Martin, K.; Morrissey, J.; Hruska, K.

    1982-03-01

    Two major hormonal system (PTH and vitamin D) and a minor system (calcitonin) are responsible for the regulation of calcium homeostasis. Serum ionized calcium is maintained within narrow limits by the intereactions of these hormonal systems and their effects on the intestine, the kidney, and the skeleton. The editorial describes in a succinct form, general aspects of PTH metabolism in view of recent information regarding the contributions of the liver, kidney, and bone to the degradation of PTH. On the basis of information accumulated concerning the peripheral metabolism of PTH, the different RIAs for PTH are also discussed.

  10. Influence of parathyroid hormone on bone cell ultrastructure

    SciTech Connect

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

    1981-05-01

    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)

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

    E-print Network

    Eisenberg, Rahel E. (Rahel Esther)

    2009-01-01

    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 ...

  12. Turmeric inhibits parathyroid hormone-related protein (PTHrP) secretion from human rheumatoid synoviocytes

    E-print Network

    Frye, J.; Timmermann, Barbara N.; Funk, J.

    2012-06-12

    Excessive production of parathyroid hormone-related protein (PTHrP) by tumor-like synoviocytes contributes to joint destruction in rheumatoid arthritis (RA). Having previously demonstrated that curcuminoid-only and essential oil-only fractions...

  13. Effect of parathyroid hormone on myocardial energy metabolism in the rat

    Microsoft Academic Search

    Ryszard Baczynski; Shaul G Massry; Ricardo Kohan; Maria Magott; Yahya Saglikes; Nachman Brautbar

    1985-01-01

    Effect of parathyroid hormone on myocardial energy metabolism in the rat. This study examined the effect of parathyroid hormone (PTH) on myocardial energy production, transfer, and utilization. Rats (150 to 200 g) were injected with 1-84 PTH, 200 U\\/day i.p., or 1-34 PTH, 200 or 300 U\\/day i.p., for 4 days. Control animals received the vehicle only. The effect of

  14. Recombinant expression and purification of the N-terminal extracellular domain of the parathyroid hormone receptor

    Microsoft Academic Search

    Paul Monaghan; Iwona Woznica; Beenu Moza; Eric J. Sundberg; Michael Rosenblatt

    2007-01-01

    Our goal is to elucidate the nature of the bimolecular interaction of parathyroid hormone (PTH) with its receptor, the parathyroid hormone receptor type-1 (PTHR1). In order to study this interaction, we are aiming to obtain a three-dimensional structure of the PTH–PTHR1 bimolecular complex. Due to the very low expression levels of endogenous PTHR1, a recombinant form is required for structural

  15. Desensitization of parathyroid hormone receptors on cultured bone cells

    SciTech Connect

    Pun, K.K.; Ho, P.W.; Nissenson, R.A.; Arnaud, C.D. (Univ. of Hong Kong (Hong Kong))

    1990-12-01

    Administration of excessive amounts of parathyroid hormone (PTH) in the treatment of osteoporosis can reverse the beneficial effects of a low-dose, intermittent regime. To investigate the direct actions and the possible cellular mechanisms of PTH in inducing desensitization of PTH receptors, we studied the effects of desensitization on rat osteoblastic UMR-106 cells. When the osteoblasts were preincubated with bPTH-(1-34), complete refractoriness to a subsequent challenge with the hormone developed within 1 h and at hormone concentrations as low as 5 nM. When osteoblasts thus desensitized were incubated in hormone-free medium, recovery of the cAMP responses began within 2 h and reached maximum after 16 h. Cycloheximide did not affect the process of desensitization. (Nle8,Nle18,Tyr34)bPTH-(3-34)amide significantly impaired the desensitization process by PTH-(1-34) but did not have stimulatory effect on cAMP responses. No significant heterologous desensitization was obvious after preincubation with isoprenaline (50 microM), prostaglandin E1 (50 microM), or prostaglandin E2 (50 microM) for 2 h. Binding experiments with (125I)PLP-(1-36)amide after desensitization revealed that there was an approximate twofold decrease in receptor affinities as analyzed by Scatchard analysis, showing that the decrease in affinity was prominent in the process of desensitization. When the cells were treated with monensin during desensitization, PTH challenge after desensitization produced significantly lower cyclic AMP responses. Recovery after desensitization occurred over a period of 16 h. Inclusion of monensin, but not cycloheximide, impaired the recovery. The results show that homologous desensitization of rat osteoblasts to PTH is brought about by the occupancy of receptors by PTH-(1-34) but not by cAMP generation itself.

  16. Parathyroid Hormone, Cognitive Function and Dementia: A Systematic Review

    PubMed Central

    Lourida, Ilianna; Thompson-Coon, Jo; Dickens, Chris M.; Soni, Maya; Ku?ma, El?bieta; Kos, Katarina; Llewellyn, David J.

    2015-01-01

    Background Metabolic factors are increasingly recognized to play an important role in the pathogenesis of Alzheimer’s disease and dementia. Abnormal parathyroid hormone (PTH) levels play a role in neuronal calcium dysregulation, hypoperfusion and disrupted neuronal signaling. Some studies support a significant link between PTH levels and dementia whereas others do not. Methods We conducted a systematic review through January 2014 to evaluate the association between PTH and parathyroid conditions, cognitive function and dementia. Eleven electronic databases and citation indexes were searched including Medline, Embase and the Cochrane Library. Hand searches of selected journals, reference lists of primary studies and reviews were also conducted along with websites of key organizations. Two reviewers independently screened titles and abstracts of identified studies. Data extraction and study quality were performed by one and checked by a second reviewer using predefined criteria. A narrative synthesis was performed due to the heterogeneity of included studies. Results The twenty-seven studies identified were of low and moderate quality, and challenging to synthesize due to inadequate reporting. Findings from six observational studies were mixed but suggest a link between higher serum PTH levels and increased odds of poor cognition or dementia. Two case-control studies of hypoparathyroidism provide limited evidence for a link with poorer cognitive function. Thirteen pre-post surgery studies for primary hyperparathyroidism show mixed evidence for improvements in memory though limited agreement in other cognitive domains. There was some degree of cognitive impairment and improvement postoperatively in observational studies of secondary hyperparathyroidism but no evident pattern of associations with specific cognitive domains. Conclusions Mixed evidence offers weak support for a link between PTH, cognition and dementia due to the paucity of high quality research in this area. PMID:26010883

  17. Primary hyperparathyroidism: four- to eight-year postoperative follow-up demonstrating persistent functional insignificance of microscopic parathyroid hyperplasia and decreased autonomy of parathyroid hormone release.

    PubMed Central

    Harrison, T S; Duarte, B; Reitz, R E; Princenthal, R; Seaton, J F; Badder, E M; Graham, W P

    1981-01-01

    Thirty-nine patients with primary hyperparathyroidism were studied four to eight years after their initial operation. In six patients, both the pathologist and surgeon agreed on the diagnosis of solitary adenoma; in 16 patients, the surgeon diagnosed solitary adenoma and the pathologist parathyroid hyperplasia (microscopic hyperplasia). In 16 patients, primary chief cell hyperplasia was agreed upon by the pathologist and surgeon. In the 16 patients with microscopic hyperplasia, there have been no long-term recurrences of hypercalcemia, but, in two patients, plasma parathyroid hormone levels are high. Parathyroid hormone--total calcium regression curves demonstrate significant preoperative correlation in solitary adenoma, p less than 0.01, and primary chief cell hyperplasia, p less than 0.05. After operation, significant correlations were not found between parathyroid hormone and total calcium. T-testing slope differences of pre- and postoperative parathyroid hormone--total calcium regression curves demonstrates a significant (p less than 0.01) shift to the right of the microscopic hyperplasia patients after operation, moving them to a broader range of total calcium per picogram parathyroid hormone. We conclude that 1) in primary hyperparathyroidism, positive regulation of total calcium by autonomously released parathyroid hormone exists in patients with solitary adenoma and chief cell hyperplasia; 2) autonomously functioning parathyroid tissue has been removed by operation for solitary adenoma with coexistent microscopic parathyroid hyperplasia. In this four- to eight-year follow-up period, it is clear that microscopic parathyroid hyperplasia is not associated with recurrent hypercalcemia. Two functionally distinct forms of parathyroid suppression are suggested; positively regulated microscopic hyperplasia and negatively regulated pathologically suppressed glands. PMID:7283504

  18. A new analog of calcitriol, 19-nor-1,25-(OH) 2D 2, suppresses parathyroid hormone secretion in uremic rats in the absence of hypercalcemia

    Microsoft Academic Search

    Eduardo Slatopolsky; Jane Finch; Cindy Ritter; Masashi Denda; Jeremiah Morrissey; Alex Brown; Hector DeLuca

    1995-01-01

    The active metabolite of vitamin D, calcitriol (1?,25-(OH)2D3), suppresses parathyroid hormone (PTH) gene transcription. Although 1?,25-(OH)2D3 is effective in suppressing secondary hyperparathyroidism (SH) in uremic patients, the mandatory use of large amounts of calcium salts to control serum phosphorus may preclude, in some patients, the use of ideal therapeutic doses of 1?,25-(OH)2D3 because of hypercalcemia. We have studied a new

  19. Catabolic and anabolic actions of parathyroid hormone on the skeleton

    PubMed Central

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

    2015-01-01

    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

  20. Parathyroid hormone is not an inhibitor of lipoprotein lipase activity.

    PubMed

    Arnadottir, M; Nilsson-Ehle, P

    1994-01-01

    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

  1. Identification of a renal receptor for parathyroid hormone by photoaffinity radiolabeling using a synthetic analogue

    SciTech Connect

    Coltera, M.D.; Potts, J.T.; Rosenblatt, M.

    1981-10-01

    To identify a parathyroid hormone-binding component in renal membranes, a biologically active photoaffinity radioligand of parathyroid hormone was designed using chemical strategies based on the experience of earlier structure-activity studies. The sulfur-free, oxidation-resistant, synthetic analogue of bovine parathyroid hormone (bPTH), (Nle-8,Nle-18,Tyr-34) bPTH-(1-34) amide, was radiolabeled with /sup 125/iodine. Two photolabile moieties, 4-fluoro-3-nitrophenyl azide and N-succinimidyl-6(4' -azido-2' -nitrophenyl amino)-hexanoate, were separately conjugated to iodinated peptide under conditions favoring coupling through lysine side chains rather than the NH/sub 2/-terminal amino group. Concurrent studies established that a photolabile analogue was fully active in the renal adenylate cyclase assay. After incubation of both photolabile analogues in darkness with renal membranes in the presence or absence of competing hormone, exposure to light covalently linked the analogues to membrane components. Membranes were then solubilized, reduced, and fractionated on sodium dodecyl sulfate poly- acrylamide gels. Radioautographs of the gels showed four to six labeled membrane components for each analogue in the absence of competing hormone, but only one band failed to label in the presence of competing hormone. This band labeled in the presence of inactive synthetic fragments of parathyroid hormone, and was not identified in membrane preparations derived from a renal cell line that is not parathyroid hormone-responsive. The migration of the band (M/sub r/ approx. = 70,000) was identical regardless of the photolabile analogue employed. These studies provide a technique useful for further study of the interactions of parathyroid hormone and receptor in various target tissues and for receptor purification and characterization.

  2. The combined effect of parathyroid hormone and bone graft on implant fixation

    PubMed Central

    Daugaard, H.; Elmengaard, B.; Andreassen, T. T.; Baas, J.; Bechtold, J. E.; Sřballe, K.

    2013-01-01

    Impaction allograft is an established method of securing initial stability of an implant in arthroplasty. Subsequent bone integration can be prolonged, and the volume of allograft may not be maintained. Intermittent administration of parathyroid hormone has an anabolic effect on bone and may therefore improve integration of an implant. Using a canine implant model we tested the hypothesis that administration of parathyroid hormone may improve osseo-integration of implants surrounded by bone graft. In 20 dogs a cylindrical porous-coated titanium alloy implant was inserted into normal cancellous bone in the proximal humerus and surrounded by a circumferential gap of 2.5 mm. Morsellised allograft was impacted around the implant. Half of the animals were given daily injections of human parathyroid hormone (1-34) 5 ?g/kg for four weeks and half received control injections. The two groups were compared by mechanical testing and histomorphometry. We observed a significant increase in new bone formation within the bone graft in the parathyroid hormone group. There were no significant differences in the volume of allograft, bone-implant contact or in the mechanical parameters. These findings suggest that parathyroid hormone improves new bone formation in impacted morsellised allograft around an implant and retains the graft volume without significant resorption. Fixation of the implant was neither improved nor compromised at the final follow-up of four weeks. PMID:21196558

  3. Vitamin D, steroid hormones, and autoimmunity.

    PubMed

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

    2014-05-01

    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

  4. Supplementation with 1000 IU vitamin D/d leads to parathyroid hormone suppression, but not increased fractional calcium absorption, in 4-8-y-old children: A double-blind randomized controlled trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of vitamin D supplementation in healthy prepubertal children on physiologic outcomes have not been investigated. The objective was to evaluate the effects of supplementation with 1000 IU vitamin D(3)/d on calcium absorption. In a double-blind, placebo-controlled trial, we randomly assign...

  5. Parathyroid Hormone Therapy Mollifies Radiation-Induced Biomechanical Degradation in Murine Distraction Osteogenesis

    PubMed Central

    Deshpande, Sagar S.; Gallagher, Katherine K.; Donneys, Alexis; Tchanque-Fossuo, Catherine N.; Sarhaddi, Deniz; Nelson, Noah S.; Chepeha, Douglas B.; Buchman, Steven R.

    2015-01-01

    Objective Descriptions of mandibular distraction osteogenesis for tissue replacement after oncologic resection or for defects caused by osteoradionecrosis have been limited. Previous work demonstrated radiation decreases union formation, cellularity and mineral density in mandibular distraction osteogenesis. The authors posit that intermittent systemic administration of parathyroid hormone will serve as a stimulant to cellular function, reversing radiation-induced damage and enhancing bone regeneration. Methods Twenty male Lewis rats were randomly assigned to three groups: group 1 (radiation and distraction osteogenesis, n = 7) and group 2 (radiation, distraction osteogenesis, and parathyroid hormone, n = 5) received a human-equivalent dose of 35 Gy of radiation (human bioequivalent, 70 Gy) fractionated over 5 days. All groups, including group 3 (distraction osteogenesis, n = 8), underwent a left unilateral mandibular osteotomy with bilateral external fixator placement. Distraction osteogenesis was performed at a rate of 0.3 mm every 12 hours to reach a gap of 5.1 mm. Group 2 was injected with parathyroid hormone (60 ?g/kg) subcutaneously daily for 3 weeks after the start of distraction osteogenesis. On postoperative day 40, all left hemimandibles were harvested. Biomechanical response parameters were generated. Statistical significance was considered at p ? 0.05. Results Parathyroid hormone–treated mandibles had significantly higher failure load and higher yield than did untreated mandibles. However, these values were still significantly lower than those of nonirradiated mandibles. Conclusions The authors have successfully demonstrated the therapeutic efficacy of parathyroid hormone to stimulate and enhance bone regeneration in their irradiated murine mandibular model of distraction osteogenesis. Anabolic regimens of parathyroid hormone, a U.S. Food and Drug Administration–approved drug on formulary, significantly improve outcomes in a model of postoncologic craniofacial reconstruction. PMID:23806959

  6. Parathyroid Disorders

    MedlinePLUS

    ... completely different. The parathyroid glands make parathyroid hormone (PTH), which helps your body keep the right balance ... it disrupts this balance. If they secrete extra PTH, you have hyperparathyroidism, and your blood calcium rises. ...

  7. Wintertime Vitamin D Deficiency in Male Adolescents: Effect on Parathyroid Function and Response to Vitamin D3 Supplements

    Microsoft Academic Search

    J. Guillemant; H.-T. Le; A. Maria; A. Allemandou; G. Pérčs; S. Guillemant

    2001-01-01

    :   The first part of this study consisted of an 18 month follow-up of the vitamin D status and parathyroid function in a group\\u000a of 54 French male adolescents, aged from 13 to 16 years old and all pupils of a jockey training school. During the 18 month\\u000a period four samplings were made, one every 6 months. The first was

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

    PubMed

    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

    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

  9. 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...

  10. Regulation of Phosphate Transport in the Renal Tubule through Parathyroid Hormone Receptor: Unexpected Pathways

    Microsoft Academic Search

    Caroline Silve; Gérard Friedlander

    1998-01-01

    The recent molecular identification of parathyroid hormone (PTH) receptors, on the one hand, and Napi cotransporters, on the other hand, has enabled the development of powerful tools to boost the study of the regulation of renal Pi transport by PTH, a regulation which stands at a crucial point in the physiology and pathophysiology of Pi homeostasis. The aim of this

  11. Parathyroid hormone-related protein: Primary osteolytic factor produced by breast tumor cells in vitro?

    Microsoft Academic Search

    Arnold Tabuenca; Subburaman Mohan; Carlos A. Garberoglio; Patrick I. Borgen; Thomas Rosol; Thomas A. Linkhart

    1995-01-01

    Tumor cells in bone metastases are thought to induce bone resorption primarily by releasing paracrine factors. Parathyroid hormone related protein (PTHrp) has been proposed to mediate osteolytic activity of many tumors. PTHrp is produced by 40% to 60% of breast tumors and is elevated in the serum of up to 50% of patients with breast cancer metastases to bone. Most

  12. Intrauterine expression of parathyroid hormone-related protein in normal and pre-eclamptic pregnancies

    Microsoft Academic Search

    N. E. Curtis; R. G. King; J. M. Moseley; P. W. M. Ho; G. E. Rice; M. E. Wlodekd

    1998-01-01

    Maternal hypertension, vasoconstriction and placental insufficiency are features of pre-eclampsia. Alterations in calcium homeostasis and in the production of calciotropic hormones and vasoactive agents have also been described in association with pre-eclampsia. Parathyroid hormone-related protein (PTHrP) is abundantly expressed in intrauterine tissues during normal pregnancy and has roles in fetal growth and calcium homeostasis, placental calcium transport and vascular tone

  13. Comparison of renal and osseous binding of parathyroid hormone and hormonal fragments

    SciTech Connect

    Demay, M.; Mitchell, J.; Goltzman, D.

    1985-11-01

    The authors compared receptor binding and adenylate cyclase stimulation of intact bovine parathyroid hormone (bPTH)-(1-84) and the synthetic amino-terminal fragments, bPTH-(1-34) and rat PTH (rPTH)-(1-34). In both canine renal membranes and cloned rat osteosarcoma cells the amino-terminal fragments bound to a single order of sites; the affinity of rPTH-(1-34) exceeded that of bPTH-(1-34), correlating with its higher potency in stimulating adenylate cyclase. In studies with oxidized bPTH-(1--84), the middle and carboxyl regions of intact PTH were found to bind to both tissues but with higher affinity to osteosarcoma cells than to renal membranes. Our results demonstrate that rPTH-(1--34) is the most favorable probe of amino-terminal PTH binding and the most potent of the PTH peptides in stimulating renal and osseous adenylate cyclase. The results also show that midregion and carboxyl determinants within intact PTH contribute to hormone binding, which does not correlate with adenylate cyclase activation and appears more significant for skeletal than for renal binding.

  14. A new analog of 1,25-(OH) 2D 3, 19NOR1,25-(OH) 2D 2, suppresses serum PTH and parathyroid gland growth in uremic rats without elevation of intestinal vitamin D receptor content

    Microsoft Academic Search

    Fumiaki Takahashi; Jane L. Finch; Masashi Denda; Adriana S. Dusso; Alex J. Brown; Eduardo Slatopolsky

    1997-01-01

    We have previously reported that 19-nor-1,25-(OH)2D2, a new analog of 1,25-(OH)2D3, suppresses parathyroid hormone (PTH) secretion in uremic rats in the absence of hypercalcemia or hyperphosphatemia. In the current study, we examined the effect of 19-nor-1,25-(OH)2D2on parathyroid gland growth and intestinal vitamin D receptor (VDR) content. After induction of uremia by 5\\/6 nephrectomy, rats were divided into five experimental groups

  15. Human parathyroid hormone-related protein and human parathyroid hormone receptor type 1 are expressed in human medulloblastomas and regulate cell proliferation and apoptosis in medulloblastoma-derived cell lines

    Microsoft Academic Search

    Marco Gessi; Giovanni Monego; Gabriella Calviello; Paola Lanza; Felice Giangaspero; Andrea Silvestrini; Libero Lauriola; Franco O. Ranelletti

    2007-01-01

    Human parathyroid hormone-related protein (hPTHrP), identified in patients with paraneoplastic hypercalcemia and expressed\\u000a by different cell types during development and adult life, plays important roles in many human neoplasms. Immunohistochemical\\u000a and RT-PCR analyses of hPTHrP and human parathyroid hormone receptor type 1 (PTHR-1) in primary medulloblastoma confirmed\\u000a their expression in both classic and desmoplastic variants at RNA and protein levels.

  16. Upregulation of calcitriol during pregnancy and skeletal recovery after lactation do not require parathyroid hormone.

    PubMed

    Kirby, Beth J; Ma, Yue; Martin, Heather M; Buckle Favaro, Kerri L; Karaplis, Andrew C; Kovacs, Christopher S

    2013-09-01

    Pregnancy invokes a doubling of intestinal calcium absorption whereas lactation programs skeletal resorption to provide calcium to milk. Postweaning bone formation restores the skeleton's bone mineral content (BMC), but the factors that regulate this are not established. We used Pth-null mice to test whether parathyroid hormone (PTH) is required for postweaning skeletal recovery. On a normal 1% calcium diet, wild-type (WT) and Pth-null mice each gained BMC during pregnancy, declined 15% to 18% below baseline during lactation, and restored the skeleton above baseline BMC within 14 days postweaning. A 2% calcium diet reduced the lactational decline in BMC without altering the gains achieved during pregnancy and postweaning. The hypocalcemia and hyperphosphatemia of Pth-null mice normalized during lactation and serum calcium remained normal during postweaning. Osteocalcin and propeptide of type 1 collagen (P1NP) each rose significantly after lactation to similar values in WT and Pth-null. Serum calcitriol increased fivefold during pregnancy in both genotypes whereas vitamin D binding protein levels were unchanged. Absence of PTH blocked a normal rise in fibroblast growth factor-23 (FGF23) during pregnancy despite high calcitriol. A 30-fold higher expression of Cyp27b1 in maternal kidneys versus placenta suggests that the pregnancy-related increase in calcitriol comes from the kidneys. Conversely, substantial placental expression of Cyp24a1 may contribute significantly to the metabolism of calcitriol. In conclusion, PTH is not required to upregulate renal expression of Cyp27b1 during pregnancy or to stimulate recovery from loss of BMC caused by lactation. A calcium-rich diet in rodents suppresses skeletal losses during lactation, unlike clinical trials that showed no effect of supplemental calcium on lactational decline in BMC. PMID:23505097

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

    Microsoft Academic Search

    EDUARDO A SLATOPOLSKY; STEVEN K BURKE; MAUREEN A DILLON

    1999-01-01

    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

  18. Coexpression and stimulation of parathyroid hormone receptor positively regulates slowly activating IsK channels expressed in Xenopus oocytes

    Microsoft Academic Search

    Siegfried Waldegger; Gertraud Raber; Hartmut Süßbrich; J Peter Ruppersberg; B Fakler; Heini Murer; Florian Lang; Andreas E Busch

    1996-01-01

    Coexpression and stimulation of parathyroid hormone receptor positively regulates slowly activating IsK channels expressed in Xenopus oocytes. Expression of the IsK protein in Xenopus oocytes induced the characteristically slow, voltage-dependent outward currents. Superfusion with the parathyroid hormone (PTH) peptide 1–34 had no effect on IsK when expressed alone, but increased IsK when IsK was coexpressed with the PTH-receptor. PTH receptor

  19. N-terminal phosphorylation of parathyroid hormone (PTH) abolishes its receptor activity.

    PubMed

    Kumar, Amit; Gopalswamy, Mohanraj; Wishart, Clare; Henze, Mathias; Eschen-Lippold, Lennart; Donnelly, Dan; Balbach, Jochen

    2014-11-21

    The parathyroid hormone (PTH) is an 84-residue peptide, which regulates the blood Ca(2+) level via GPCR binding and subsequent activation of intracellular signaling cascades. PTH is posttranslationally phosphorylated in the parathyroid glands; however, the functional significance of this processes is not well characterized. In the present study, mass spectrometric analysis revealed three sites of phosphorylation, and NMR spectroscopy assigned Ser1, Ser3, and Ser17 as modified sites. These sites are located at the N-terminus of the hormone, which is important for receptor recognition and activation. NMR shows further that the three phosphate groups remotely disturb the ?-helical propensity up to Ala36. An intracellular cAMP accumulation assay elucidated the biological significance of this phosphorylation because it ablated the PTH-mediated signaling. Our studies thus shed light on functional implications of phosphorylation at native PTH as an additional level of regulation. PMID:25158085

  20. Serum parathyroid hormone and risk of adverse outcomes in patients with stable coronary heart disease

    Microsoft Academic Search

    Norma Christine Grandi; Lutz Philipp Breitling; Harry Hahmann; Bernd Wüsten; Winfried März; Dietrich Rothenbacher; Hermann Brenner

    2011-01-01

    Background and objectiveRecent longitudinal studies have suggested an association of high serum parathyroid hormone levels (PTH) with elevated cardiovascular risk in the general population. This study presents analyses of the prognostic value of baseline PTH for subsequent cardiovascular events and all-cause mortality in a high-risk population with stable coronary heart disease.MethodsBased on measurements of PTH levels in 1133 patients recruited

  1. The influence of parathyroid hormone on the adult hematopoietic stem cell niche

    Microsoft Academic Search

    Narges Rashidi; Gregor B. Adams

    2009-01-01

    Adult hematopoietic stem cells (HSCs) reside in the bone marrow in stable microenvironments known as the stem cell niche.\\u000a One key component of the stem cell niche is cells of the osteoblastic lineage. Factors that are known to affect osteoblast\\u000a activity, such as parathyroid hormone (PTH), have also been shown to affect the HSCs. Treatment of mice with PTH has

  2. Comparison of 1-84 and intact parathyroid hormone assay in pediatric dialysis patients

    Microsoft Academic Search

    Rita D. Sheth; Stuart L. Goldstein

    2005-01-01

    The non-invasive diagnosis of renal osteodystrophy (ROD) in patients with end-stage renal disease (ESRD) remains dependent on the determination of an accurate parathyroid hormone (PTH) level. Older assays that determine the “intact” PTH molecule are known to cross react with various PTH fragments, resulting in overestimation of PTH levels. Recently, assays that determine the whole 1-84 PTH molecule have been

  3. Parathyroid hormone regulation of Na + \\/H + exchange in opossum kidney cells: polarity and mechanisms

    Microsoft Academic Search

    Corinna Helmle-Kolb; Marshall H. Montrose; Heini Murer

    1990-01-01

    In previous work we have shown that parathyroid hormone (PTH) inhibits Na+\\/H+ exchange in cellular suspensions of OK (oppossum kidney) cells (an established renal epithelial cell line) in a dose-dependent manner. PTH effects could be mimicked by pharmacological activation of both protein kinase A and protein kinase C (Helmle-Kolb et al. 1990). In the present paper we extend these observations

  4. Prolonged signaling at the parathyroid hormone receptor by peptide ligands targeted to a specific receptor conformation

    Microsoft Academic Search

    Makoto Okazaki; Sebastien Ferrandon; Jean-Pierre Vilardaga; Mary L. Bouxsein; John T. Potts; Thomas James Gardella

    2008-01-01

    The parathyroid hormone receptor (PTHR) is a class B G protein-coupled receptor that plays critical roles in bone and mineral ion metabolism. Ligand binding to the PTHR involves interactions to both the amino-terminal extracellular (N) domain, and transmembrane\\/extracellular loop, or juxtamembrane (J) regions of the receptor. Recently, we found that PTH(1-34), but not PTH-related protein, PTHrP(1-36), or M-PTH(1-14) (M =

  5. Parathyroid Hormone-related Protein as a Growth Regulator of Prostate Carcinoma1

    Microsoft Academic Search

    Kristiann M. Dougherty; Eric A. G. Blomme; Amy J. Koh; Janet E. Henderson; Kenneth J. Pienta; Thomas J. Rosol; Laurie K. McCauley

    Parathyroid hormone-related protein (PTHrP) is produced by prostate carcinoma cells and tumors, but little is known of its role in prostate carcinogenesis. The goal of this study was to evaluate PTHrP expression in the regulation of prostate carcinoma growth using human and animal models. PTHrP expression was assessed in prostate cancer cell lines in vitro. Seven of nine cell lines

  6. Alternative splicing of parathyroid hormone-related protein mRNA: expression and stability

    Microsoft Academic Search

    R S Sellers; A I Luchin; V Richard; R M Brena; D Lima; T J Rosol

    2004-01-01

    Parathyroid hormone-related protein (PTHrP) is a multifunctional protein that is often dysregulated in cancer. The human PTHrP gene is alternatively spliced into three isoforms, each with a unique 3'-untranslated region (38-UTR), encoding 139, 173 and 141 amino acid proteins. The regulation of PTHrP mRNA isoform expression has not been completely elucidated, but it may be affected by transforming growth factor-1

  7. Messenger RNA stability of parathyroid hormone-related protein regulated by transforming growth factor-?1

    Microsoft Academic Search

    R. S. Sellers; C. C. Capen; Thomas J. Rosol

    2002-01-01

    Humoral hypercalcemia of malignancy (HHM), a paraneoplastic syndrome associated with epithelial cancers, including squamous cell carcinoma (SCC), is due to expression and secretion of parathyroid hormone-related protein (PTHrP). Transforming growth factor-?1 (TGF?1), expressed by many tumors, has been demonstrated in vitro to increase the half-life of PTHrP mRNA. In this study, oral squamous carcinoma cells (SCC2\\/88) had a two-fold increase

  8. Hysteresis and calcium set-point for the calcium parathyroid hormone relationship in healthy horses

    Microsoft Academic Search

    Ramiro E. Toribio; Catherine W. Kohn; Richard A. Sams; Charles C. Capen; Thomas J. Rosol

    2003-01-01

    Abnormalities in calcium (Ca2+) homeostasis are reported in horses with several pathological conditions; however, there is little information on Ca2+ regulation in horses. The objectives of the present study were to determine the Ca2+ set-point in healthy horses, to determine whether the Ca2+\\/parathyroid hormone (PTH) response curves were characterized by hysteresis, and to determine if the order of experimentally induced

  9. Kinetic analysis of the rapid intraoperative parathyroid hormone assay in patients during operation for hyperparathyroidism

    Microsoft Academic Search

    Steven K. Libutti; H. Richard Alexander; David L. Bartlett; Maureen L. Sampson; Mark E. Ruddel; Monica Skarulis; Stephen J. Marx; Allen M. Spiegel; William Simmonds; Alan T. Remaley

    1999-01-01

    Background: Rapid intraoperative parathyroid hormone (RI-PTH) assay is used to guide adequacy of resection during operation for hyperparathyroidism. We compared the RI-PTH assay (15 minutes) with a standard PTH assay, determined whether the PTH half-life varied between patients, and constructed a kinetic analysis of the RI-PTH data. Methods: Forty-five patients with hyperparathyroidism had blood sampled at baseline and at times

  10. Parathyroid hormone (1–34) increases vertebral bone mass, compressive strength, and quality in old rats

    Microsoft Academic Search

    C. Ejersted; T. T. Andreassen; E.-M. Hauge; F. Melsen; H. Oxlund

    1995-01-01

    Human parathyroid hormone 1–34 (PITH) exerts an anabolic effect on bone in younger rats. The aim of the present study was to examine the effect of PTH on vertebral bone in 2-year-old male rats. The rats were treated with daily injections of 15 nmol\\/kg PTH or vehicle (V) for 56 days. Tetracycline and calcein were injected on day 15 and

  11. A Role for Interleukin6 in Parathyroid Hormone-Induced Bone Resorption in Vivo

    Microsoft Academic Search

    ANDREW GREY; MARY-ANN MITNICK; URSZULA MASIUKIEWICZ; BEN-HUA SUN; STUART RUDIKOFF; ROBERT L. JILKA; STAVROS C. MANOLAGAS; KARL INSOGNA

    1999-01-01

    Parathyroid hormone (PTH) exerts its regulatory effects on cal- cium homeostasis in part by stimulating the release of calcium from the skeleton. PTH stimulates bone resorption indirectly, by inducing the production by stromal\\/osteoblastic cells of paracrine agents which recruit and activate the bone-resorbing cell, the osteoclast. The iden- tity of the stromal cell\\/osteoblast-derived paracrine factor(s) respon- sible for mediating the

  12. Parathyroid hormone-related protein and calcium concentrations in milk and blood of ewes

    Microsoft Academic Search

    N. Kocabagli; J.-L. Riond; K. Küng; M. Wanner

    1995-01-01

    Parathyroid hormone-related protein (PTHrP) and calcium (Ca) concentrations were measured 2 to 3 months postpartum in milk and plasma or serum of 22 ewes by the use of commercial radioimmunoassay kits for PTHrP concentration, colorimetry for serum total Ca concentration (Catot), and atomic absorption spectrophotometry for milk total Ca concentration. Scatter plots did not reveal dependency between milk Ca and

  13. Anabolic effect of human parathyroid hormone fragment on trabecular bone in involutional osteoporosis: a multicentre trial

    Microsoft Academic Search

    J Reeve; P J Meunier; J A Parsons; M Bernat; O L Bijvoet; P Courpron; C Edouard; L Klenerman; R M Neer; J C Renier; D Slovik; F J Vismans; J T Potts

    1980-01-01

    After baseline studies, 21 patients with osteoporosis were treated with human parathyroid hormone fragment (PTH 1-34) given as once-daily subcutaneous injections for 6-24 months. The dose used did not cause hypercalcaemia even in the first few hours after injection. Calcium and phosphate balances improved in some patients, but there was no significant improvement in the group values. There were, however,

  14. Parathyroid hormone ablation alters erythrocyte parameters that are rescued by calcium-sensing receptor gene deletion

    PubMed Central

    Romero, Jose R.; Youte, Rodeler; Brown, Edward M.; Pollak, Martin R.; Goltzman, David; Karaplis, Andrew; Pong, Lie-Chin; Chien, Lawrence; Chattopadhyay, Naibedya; Rivera, Alicia

    2013-01-01

    The mechanisms by which parathyroid hormone (PTH) produces anemia, are unclear. Parathyroid hormone secretion is regulated by the extracellular Ca2+-sensing receptor. We investigated the effects of ablating PTH on hematological indices and erythrocytes volume regulation in wild-type, PTH-null and Ca2+-sensing receptor-null/PTH-null mice. The erythrocyte parameters were measured in whole mouse blood and volume regulatory systems were determined by plasma membrane K+ fluxes and osmotic fragility was measured by hemoglobin determination at varying osmolarities. We observed that the absence of PTH significantly increases mean erythrocyte volume and reticulocyte counts, while decreasing erythrocyte counts, hemoglobin, hematocrit, and mean corpuscular hemoglobin concentration. These changes were accompanied by increases in erythrocyte cation content, a denser cell population and increased K+ permeability, which were in part mediated by activation of the K+/Cl? cotransporter and Gardos channel. In addition we observed that erythrocyte osmotic fragility in PTH-null compared with wild-type mice was enhanced. When Ca2+-sensing receptor gene was deleted on the background of PTH-null mice, we observed that several of the alterations in erythrocyte parameters of PTH-null mice were largely rescued, particularly those related to erythrocyte volume, K+ fluxes and osmotic fragility, and became similar to those observed in wild-type mice. Our results demonstrate that Ca2+-sensing receptor and parathyroid hormone are functionally coupled to maintain erythrocyte homeostasis. PMID:23528155

  15. Quantitation of PTH (parathyroid hormone) in biological fluids. Draft report

    SciTech Connect

    Hindman, B.E.; Halpern, E.P.; Schlaff, S.; Mason, R.

    1982-01-01

    Radioimmunoassay -- rather than immunoradiometry, bioassay or cytochemical assay -- is the PTH determination of the future. The commercially available radioimmunoassays have been developed with nonhuman reagents. Those using antisera that react with C-terminal circulating fragments distinguish normal from hyperparathyroid subjects better than those that recognize the intact PTH. The i-PTH has utility in selective venous catheterization for preoperative localization of hyperfunctioning parathyroid tissue. However, the ability of these antisera to detect human N- and C-terminal fragments has been determined by using bovine PTH fragments, since fragments of human PTH are not commercially available. The production of antibodies by humans or animals is dependent on the injected antigen causing the host to make antibodies. Antibody may not only differ from species to species but from individual to individual within the same species. Antibody differences can also be encountered from one immunization to another. These factors account for the nonspecificity and noncorrelation differences between assays, and do not reflect the true in vivo situation.

  16. Ultrasensitive Impedimetric Biosensor Fabricated by a New Immobilisation Technique for Parathyroid Hormone.

    PubMed

    Özcan, Hakk? Mevlüt; Yildiz, Kübra; Çakar, Cansu; Aydin, Tuba; Asav, Engin; Sa?iro?lu, Ayten; Sezgintürk, Mustafa Kemal

    2015-07-01

    This paper presents a novel ultrasensitive and rapid impedimetric biosensor with new immobilisation materials for parathyroid hormone (PTH) with the aim to determine the PTH level in serum for the diagnosis and monitoring of parathyroid diseases such as hyperparathyroidism, adenoma, and thyroid cancer. The interaction between PTH and the biosensor was investigated with an electrochemical method. The biosensor was based on the gold electrode modified by mercaptohexanol (6-MHL). Anti-parathyroid hormone (anti-PTH) was covalently immobilised onto a self-assembled monolayer (SAM) by using epiclorhidrina (EPI) with ethanolamine (EA). The EPI-EA interaction represents the first use of these for the construction of biosensors in published reports. The immobilisation of the anti-PTH was monitored by electrochemical impedance spectroscopy, cyclic voltammetry and scanning electron microscopy (SEM) techniques. After the optimisation studies of immobilisation materials such as 6-MHL, EPI, EA and glutaraldehyde, linearity, repeatability and sensitivity of biosensor were evaluated as the performance of biosensor. PTH was detected within a linear range of 0.1-0.6 pg/ml, and the detection limit was 0.1 fg/ml. The specificity of the biosensor was also investigated. Finally, the described biosensor was used to detect the PTH levels in artificial serum samples. PMID:25935225

  17. Nonlinear dynamics in pulsatile secretion of parathyroid hormone in normal human subjects

    NASA Astrophysics Data System (ADS)

    Prank, Klaus; Harms, Heio; Brabant, Georg; Hesch, Rolf-Dieter; Dämmig, Matthias; Mitschke, Fedor

    1995-03-01

    In many biological systems, information is transferred by hormonal ligands, and it is assumed that these hormonal signals encode developmental and regulatory programs in mammalian organisms. In contrast to the dogma of endocrine homeostasis, it could be shown that the biological information in hormonal networks is not only present as a constant hormone concentration in the circulation pool. Recently, it has become apparent that hormone pulses contribute to this hormonal pool, which modulates the responsiveness of receptors within the cell membrane by regulation of the receptor synthesis, movement within the membrane layer, coupling to signal transduction proteins and internalization. Phase space analysis of dynamic parathyroid hormone (PTH) secretion allowed the definition of a (in comparison to normal subjects) relatively quiet ``low dynamic'' secretory pattern in osteoporosis, and a ``high dynamic'' state in hyperparathyroidism. We now investigate whether this pulsatile secretion of PTH in healthy men exhibits characteristics of nonlinear determinism. Our findings suggest that this is conceivable, although on the basis of presently available data and techniques, no proof can be established. Nevertheless, pulsatile secretion of PTH might be a first example of nonlinear deterministic dynamics in an apparently irregular hormonal rhythm in human physiology.

  18. Changes in calcium phosphate on bone surfaces and in lining cells after the administration of parathyroid hormone or calcitonin

    SciTech Connect

    Norimatsu, H.; Yamamoto, T.; Ozawa, H.; Talmage, R.V.

    1982-04-01

    Small doses of parathyroid hormone and calcitonin were injected into thyroparathyroidectomized newborn rats to investigate the histological and chemical changes in bone surfaces and in mitochondrial granules of bone lining cells. Nondecalcified tissue specimens were observed under transmission electron microscope, electron probe X-ray microanalyzer, and microdiffraction after freeze substitution preparation of tibia shafts. Amorphous calcium phosphate, which appears as clusters and globules by this freeze substitution preparation, appears on the bone surfaces in a short time after the administration of a small dose of calcitonin. The Ca:PO4 ratio in the mitochondria of bone lining cells rises slightly with a small dose of parathyroid hormone and is reduced with a small dose of calcitonin. These data support the postulate that both parathyroid hormone and calcitonin act directly on bone lining cells in the process of influencing calcium concentrations of blood and temporarily storing calcium at bone surfaces.

  19. Persistent nephrogenic diabetes insipidus, tubular proteinuria, aminoaciduria, and parathyroid hormone resistance following longterm lithium administration.

    PubMed Central

    Neithercut, W. D.; Spooner, R. J.; Hendry, A.; Dagg, J. H.

    1990-01-01

    We report a patient who developed persistent nephrogenic diabetes insipidus associated with renal tubular acidosis, renal resistance to parathyroid hormone, aminoaciduria and proximal tubule pattern proteinuria in the presence of a reduced glomerular filtration rate (19-24 ml/min). A review of the previous reports of persistent nephrogenic diabetes insipidus revealed that in all patients the glomerular filtration rate had been less than 60 ml/min at presentation. Chronic renal failure may therefore predispose to the development of persistent nephrogenic diabetes insipidus in patients receiving lithium. PMID:2170960

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

    SciTech Connect

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

    2008-08-07

    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.

  1. Parathyroid Hormone is Related to Dysplasia and a Higher Rate of Distal Colorectal Adenoma in Women but Not Men.

    PubMed

    Aigner, Elmar; Stadlmayr, Andreas; Huber-Schönauer, Ursula; Zwerina, Jochen; Husar-Memmer, Emma; Niederseer, David; Eder, Sebastian K; Stickel, Felix; Pirich, Christian; Schett, Georg; Patsch, Wolfgang; Datz, Christian

    2015-08-01

    Molecular and clinical observations provide evidence for a potential role of parathyroid hormone (PTH) in colorectal cancer development. We therefore aimed to assess the association of PTH with regard to colorectal cancer precursor lesions. A cohort of 1432 participants, 777 men, 58.4?±?9.6 years and 701 women, 59.1?±?10.6 years, undergoing screening colonoscopy were allocated to PTH serum concentrations either above or below 55 ng/L. The number, localization, size, and histology of the polypoid lesions detected during screening colonoscopy were recorded according to PTH serum concentrations. Serum PTH concentrations were not different between men and women. Women with PTH serum concentrations above the cut-off had significantly more adenomas (13/40; 32.5 %) of the distal colon compared to women below the cut-off (91/659; 13.8 %; P?=?0.001). Additionally, the rate of dysplasia in adenomas of the distal colon was higher in women with high compared to low PTH concentrations (P?=?0.001). These findings remained robust after adjustments for serum vitamin D, age, plasma creatinine, BMI, diabetes, and liver steatosis. No associations were observed between serum PTH concentrations and colorectal lesions in men. These data suggest that elevated PTH serum concentrations might have a role in colorectal cancer development as indicated by higher rates of adenomas, specifically with dysplasia, in women. The role of PTH in colon carcinogenesis and its sex specificity deserve further study. PMID:26021763

  2. Effects of thyroparathyroidectomy, parathyroid hormone, and PTHrP on kidneys of ovine fetuses.

    PubMed

    MacIsaac, R J; Horne, R S; Caple, I W; Martin, T J; Wintour, E M

    1993-01-01

    The fetal parathyroid glands and parathyroid hormone-related protein (PTHrP) have been shown to be important regulators of fetal calcium metabolism through their actions on the placenta and bone. This study examined the effects of fetal thyroparathyroidectomy (with thyroxine replacement) and exogenous infusion of human parathyroid hormone [PTH-(1-34)], PTHrP-(1-34), and PTHrP-(1-141) on the urinary excretion of calcium in chronically cannulated ovine fetuses during the last one-fifth of gestation. Fetal plasma total and ionized calcium concentrations were significantly lower in thyroparathyroidectomized (TxPTx) fetuses when compared with intact fetuses, but there were no significant differences in urinary excretion rates of total calcium. However, TxPTx produced a significant increase in the fractional excretion rate of total calcium and a significant decrease in the excretion of adenosine 3',5'-cyclic monophosphate (cAMP) compared with intact fetuses. Infusions of PTH-(1-34), PTHrP-(1-34), and PTHrP-(1-141) into the jugular vein of TxPTx fetuses (n = 5) at the rate of 1 nmol/h for 2 h, after a 1-nmol loading dose, significantly decreased the excretion rate of total calcium and increased the excretion rate of cAMP in fetal urine. Infusions of all three peptides resulted in significant increases in the concentration of total calcium in fetal plasma but had no effect on the plasma concentrations or urinary excretion rates of phosphate. Infusion of either PTH-(1-34), PTHrP-(1-34), or PTHrP-(1-141) also resulted in an increase in fetal urine osmolality and pH and a decrease in free water clearance in TxPTx fetuses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8430786

  3. Levels of parathyroid hormone and calcitonin in serum among atomic bomb survivors

    SciTech Connect

    Fujiwara, Saeko; Yokoyama, Naokata; Sasaki, Hideo; Kodama, Kazunori; Sposto, R.; Shimaoka, Katsutaro [Radiation Effects Research Foundation (Japan); Shiraki, Mastaka [Tokyo Metropolitan Geriatric Hospital (Japan)

    1994-01-01

    To examines the potential causes of increased levels of calcium in serum with increasing dose of atomic bomb radiation, which was obtained from the previous preliminary analysis, levels of parathyroid hormone (PTH) and calcitonin in serum were examined among 1459 subjects in Hiroshima and Nagasaki. A significant effect of radiation on levels of calcium, PTH and calcitonin in serum was found, even after patients with hyperparathyroidism were excluded. The level of calcium in serum increased with radiation dose; this can be explained partly by the increase in the level of PTH with radiation dose. However, the dose effect on calcium remained even after adjustment for PTH, calcitonin and confounding factors such as renal function, serum albumin level and medication. Parathyroid hormone increased initially by 6.8% per gray, but the dose response leveled off after about 1 Gy. The level of calcitonin increased with radiation dose, probably in part due to feedback mechanisms stimulated by the increase in calcium. However, after adjustment for the level of calcium, the increase in the level of calcitonin with dose was still found. Although the etiological mechanisms of the effect of radiation on serum levels of calcium, PTH and calcitonin are unclear, radiation exposure may affect secretion of PTH and calcitonin and regulation of calcium a long time after atomic bomb exposure. 21 refs., 3 figs., 6 tabs.

  4. Recombinant expression and purification of the N-terminal extracellular domain of the parathyroid hormone receptor.

    PubMed

    Monaghan, Paul; Woznica, Iwona; Moza, Beenu; Sundberg, Eric J; Rosenblatt, Michael

    2007-07-01

    Our goal is to elucidate the nature of the bimolecular interaction of parathyroid hormone (PTH) with its receptor, the parathyroid hormone receptor type-1 (PTHR1). In order to study this interaction, we are aiming to obtain a three-dimensional structure of the PTH-PTHR1 bimolecular complex. Due to the very low expression levels of endogenous PTHR1, a recombinant form is required for structural analysis. However, the extreme hydrophobicity of the transmembrane regions of PTHR1 makes heterologous expression of PTHR1 difficult. Therefore, we sought to express the N-terminal extracellular domain (N-ECD) of PTHR1, a region that plays a pivotal role in ligand interaction. We expressed the N-ECD in both bacterial (Escherichia coli) and insect (Sf9) cells. The form produced in E. coli, a fusion-protein with thioredoxin, is soluble. However, removal of the fusion partner from a partially purified preparation results in dramatic loss of yield of the N-ECD. Expression in Sf9 cells, however, facilitates purification of a soluble form of the N-ECD. Isothermal calorimetry demonstrates that this N-ECD binds PTH-(1-34), albeit with lower affinity than the full-length receptor. This report describes the expression and purification of milligram quantities of the isolated N-ECD of PTHR1. The receptor fragment retains the ability to bind its cognate peptide ligand, an important pre-requisite for subsequent structural studies. PMID:17448676

  5. Recombinant expression and purification of the N-terminal extracellular domain of the parathyroid hormone receptor

    PubMed Central

    Monaghan, Paul; Woznica, Iwona; Moza, Beenu; Sundberg, Eric J.; Rosenblatt., Michael

    2007-01-01

    Our goal is to elucidate the nature of the bimolecular interaction of parathyroid hormone (PTH) with its receptor, the parathyroid hormone receptor type-1 (PTHR1). In order to study this interaction, we are aiming to obtain a three-dimensional structure of the PTH—PTHR1 bimolecular complex. Due to the very low expression levels of endogenous PTHR1, a recombinant form is required for structural analysis. However, the extreme hydrophobicity of the transmembrane regions of PTHR1 makes heterologous expression of PTHR1 difficult. Therefore, we sought to express the N-terminal extracellular domain (N-ECD) of PTHR1, a region that plays a pivotal role in ligand interaction. We expressed the N-ECD in both bacterial (E. coli) and insect (Sf9) cells. The form produced in E. coli, a fusion-protein with thioredoxin, is soluble. However, removal of the fusion partner from a partially purified preparation results in dramatic loss of yield of the N-ECD. Expression in Sf9 cells, however, facilitates purification of a soluble form of the N-ECD. Isothermal calorimetry demonstrates that this N-ECD binds PTH-(1–34), albeit with lower affinity than the full-length receptor. This report describes the expression and purification of milligram quantities of the isolated N-ECD of PTHR1. The receptor fragment retains the ability to bind its cognate peptide ligand, an important pre-requisite for subsequent structural studies. PMID:17448676

  6. Phase II Trial of Parathyroid Hormone following Double Umbilical Cord Blood Transplantation

    PubMed Central

    Ballen, Karen K; Mendizabal, Adam M; Cutler, Corey; Politikos, Ioannis; Jamieson, Katarzyna; Shpall, Elizabeth J; Dey, Bimalangshu R; Attar, Eyal; McAfee, Steven; Delaney, Colleen; McCarthy, Philip; Ball, Edward D; Kamble, Ram; Avigan, David; Maziarz, Richard T; Ho, Vincent T; Koreth, John; Alyea, Edwin; Soiffer, Robert; Wingard, John R; Boussiotis, Vicki; Spitzer, Thomas R; Antin, Joseph H

    2012-01-01

    Transplantation of one or two umbilical cord blood products is a useful alternative stem cell source. However, the limited number of stem cells in the infusion results in slow engraftment. In mouse models, administration of parathyroid hormone is an effective way to enhance the ability of limited numbers of hematopoietic stem cells to support hematopoiesis. In this study, patients received either a myeloablative or a reduced intensity double umbilical cord blood transplantation followed by parathyroid hormone at 100 ?g daily for 28 days. Thirteen patients (median age 42 years) were enrolled. All patients engrafted; the median time to neutrophil and platelet engraftment >20x109 cells/L were 30 and 61 days respectively. The incidence of Grades II–IV acute GVHD was 38.5% at day 100. There were four deaths prior to Day 100, prompting early study closure. No patients receiving a myeloablative regimen relapsed. Overall survival at 6 months after transplantation was 62% and disease-free survival at 2 years was 39%. At the dose and schedule studied, there was no evidence that PTH influenced blood count recovery. PMID:22766223

  7. ALX 111: ALX1-11, parathyroid hormone (1-84) - NPS Allelix, PREOS, PTH, recombinant human parathyroid hormone, rhPTH (1-84).

    PubMed

    2003-01-01

    ALX 111 [parathyroid hormone (1-84) - NPS Allelix, recombinant human parathyroid hormone, rhPTH (1-84), PREOS] is a full-length, recombinant human parathyroid hormone. It has potential as an anti-osteoporotic agent, due to its properties as a bone formation stimulant. This profile has been selected from R&D Insight, a pharmaceutical intelligence database produced by Adis International Ltd. It has been recommended that ALX 111 should be given for 1 to 2 years and may be given in combination with an antiresorptive agent, such as estrogen or a bisphosphonate. In December 1999, Allelix Biopharmaceuticals merged with NPS Pharmaceuticals. This combined company is operating as NPS Pharmaceuticals in the US and as NPS Allelix in Canada. The merger has enabled a phase III study of ALX 111 to begin in the US, Europe and South America. NPS harmaceuticals has signed an agreement with Bio-Imaging Technologies, which will provide all image handling and analysis for this trial. Until 1994, Allelix Biopharmaceuticals and Glaxo in Canada were involved in a joint venture to investigate the efficacy of ALX 111 in osteoporosis. Allelix was subsequently, until September 1998, collaborating with Astra of Sweden in developing ALX 111. Astra had acquired exclusive worldwide rights to ALX 111 and was responsible for development of the agent. However, Astra returned all rights to ALX 111 to Allelix as a result of its merger with Zeneca to form AstraZeneca. In December 1999, Allelix Biopharmaceuticals merged with NPS Pharmaceuticals. This combined company is operating as NPS Pharmaceuticals in the US and as NPS Allelix in Canada. The merger has enabled a phase III study of ALX 111 to begin in the US, Europe and South America. The phase III trial of ALX 111 for the treatment of osteoporosis has completed patient enrolment, and phase II trials have been completed in Canada and the Netherlands. The 18-month, phase III, multicentre, placebo-controlled trial (Treatment of Osteoporosis with Parathyroid Hormone; TOP) has been designed to assess the bone-building and fracture-reducing potential of the drug, and over 2600 postmenopausal women with osteoporosis who have not received previous drug therapy for osteoporosis have been enrolled. Treatment will be completed in September 2003, but more than 75% of patients enrolled in the TOP study have chosen to enrol in an Open Label Extension Study (OLES), which allows for a total treatment period of up to 24 months. NPS Pharmaceuticals has signed an agreement with Bio-Imaging Technologies, which will provide all image handling and analysis for this trial. In September 2002, NPS Pharmaceuticals announced that it has met its patient enrolment target (n > 150) for its POWER (PTH for Osteoporotic Women on Estrogen Replacement) study; a 24-month phase III trial initiated in Europe in November 2001. In this trial, women with osteoporosis receive SC injections of ALX 111 or placebo, in combination with their existing hormone replacement therapies, to test the bone building potential of the drug. In addition to the POWER study, a clinical trial sponsored by the National Institutes of Health (NIH) is being conducted to evaluate the potential of ALX 111 to build bone in combination with another osteoporosis medication. The 'PaTH' study (PTH/alendronate) is designed to assess the effect of various combinations and sequential uses of ALX 111 and Merck's Fosamax, a drug for slowing the loss of bone due to osteoporosis. The PaTH study, initiated in May 2000 and scheduled to conclude in September 2003, involved 238 patients with postmenopausal osteoporosis. It is thought that alendronic acid and ALX 111, when administered in combination, may act in an additive manner to treat osteoporosis because they act in different ways; alendronic acid acts to inhibit resorption and ALX 111 speeds up bone formation and resorption, with a net increase in formation. Results of this study are still being analysed but preliminary results appear to be positive. The effect of ALX 111 on bone cell cultures underare still being analysed but p

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

    Microsoft Academic Search

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

    1995-01-01

    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

  9. Potential role of IGF-1 in parathyroid hormone-related renal growth induced by high protein diet in uninephrectomized rats

    Microsoft Academic Search

    Joseph Caverzasio; T Shigematsu; R Rizzoli; Jean-Philippe Bonjour

    1995-01-01

    Potential role of IGF-1 in parathyroid hormone-related renal growth induced by high protein diet in uninephrectomized rats. Recent studies indicate that parathyroidectomy (PTX) prevents the progression of kidney damage due to high protein diet in the subtotal nephrectomized rat model of chronic renal failure. Associated with this protection, the difference in the renal “compensatory” growth induced by high (HPr) as

  10. Restoration of parathyroid function after change of phosphate binder from calcium carbonate to lanthanum carbonate in hemodialysis patients with suppressed serum parathyroid hormone.

    PubMed

    Inaba, Masaaki; Okuno, Senji; Nagayama, Harumi; Yamada, Shinsuke; Ishimura, Eiji; Imanishi, Yasuo; Shoji, Shigeichi

    2015-03-01

    Control of phosphate is the most critical in the treatment of chronic kidney disease with mineral and bone disorder (CKD-MBD). Because calcium-containing phosphate binder to CKD patients is known to induce adynamic bone disease with ectopic calcification by increasing calcium load, we examined the effect of lanthanum carbonate (LaC), a non-calcium containing phosphate binder, to restore bone turnover in 27 hemodialysis patients with suppressed parathyroid function (serum intact parathyroid hormone [iPTH] ? 150 pg/mL). At the initiation of LaC administration, the dose of calcium-containing phosphate binder calcium carbonate (CaC) was withdrawn or reduced based on serum phosphate. After initiation of LaC administration, serum calcium and phosphate decreased significantly by 4 weeks, whereas whole PTH and iPTH increased. A significant and positive correlation between decreases of serum calcium, but not phosphate, with increases of whole PTH and iPTH, suggested that the decline in serum calcium with reduction of calcium load by LaC might increase parathyroid function. Serum bone resorption markers, such as serum tartrate-resistant acid phosphatase 5b, and N-telopeptide of type I collagen increased significantly by 4 weeks after LaC administration, which was followed by increases of serum bone formation markers including serum bone alkaline phosphatase, intact procollagen N-propeptide, and osteocalcin. Therefore, it was suggested that LaC attenuated CaC-induced suppression of parathyroid function and bone turnover by decreasing calcium load. In conclusion, replacement of CaC with LaC, either partially or totally, could increase parathyroid function and resultant bone turnover in hemodialysis patients with serum iPTH ? 150 pg/mL. PMID:25556148

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

    PubMed Central

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

    2013-01-01

    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

  12. Parathyroid hormone-related peptide in pancreatic neuroendocrine tumours associated with hypercalcaemia

    PubMed Central

    Papazachariou, IM; Virlos, IT

    2001-01-01

    Background Hypercalcaemia is a common paraneoplastic syndrome. In the context of pancreatic neuroendocrine tumours, it is occasionally caused by secretion of parathyroid hormone-related peptide (PTH-rP). Case outlines Two patients are reported in whom persistent hypercalcaemia was traced to a large neuroendocrine pancreatic tumour hypersecreting PTH-rP. Resection of the tumour reduced serum levels of calcium and PTH-rP transiently in each case until the patient developed bulky metastatic disease. A 33-year-old woman remained hypercalcaemic after the removal of all four hyperplastic parathyroid glands had rendered circulating parathormone levels undetectable. Radical distal pancreatectomy was followed over the next 4 years by operative debulking of liver metastases, multiple hepatic artery embolisations.octreotide injections and repeated admissions for intravenous fluid and biphosphonate therapy. A 41-year-old man presented with hypercalcaemia as well as features of somatostatinoma syndrome. Symptomatic improvement after radical distal pancreatectomy was short-lived, and hepatic artery embolisation failed to control his rapidly progressive disease. Discussion Malignant hypercalcaemia associated with a neuroendocrine pancreatic tumour hypersecreting PTH-rP is difficult to treat and can be life-threatening. Aggressive surgical treatment is recommended initially, while somatostatin analogues and hepatic artery embolisation are alternative therapeutic options for metastatic disease. PMID:18333019

  13. Parathyroid Hormone after Adenectomy for Primary Hyperparathyroidism. A Study of Peptide Hormone Elimination Kinetics in Humans

    Microsoft Academic Search

    G. W. Maier; M. E. KREIS; W. RENN; P. L. PEREIRA; H. U. HARING; H. D. BECKER

    1998-01-01

    The study of the elimination kinetics of peptide hormones in hu- mans is limited, because determining hormone levels in different compartments is difficult. We calculated the elimination kinetics of intact PTH (1- 84) after adenoma removal in primary hyperparathy- roidism, based on a 2-compartment model. In 12 patients, blood sam- ples were drawn in short intervals preoperatively, during surgery, and

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

    SciTech Connect

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

    1985-01-01

    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.

  15. [Therapeutic agents for disorders of bone and calcium metabolism--Parathyroid hormone in weekly subcutaneous injection].

    PubMed

    Uzawa, Toyonobu

    2007-01-01

    The parathyroid hormone (PTH) that is marketed outside Japan is for daily administration. It has been proven to increase bone mass and prevent fractures, and the effects are very strong. However, data suggest that daily administration of PTH increases bone resorption. By contrast, weekly administration of PTH, which is being developed in Japan, actually decreases bone resorption, and data suggest that this regimen maintains a good balance between bone formation (predominant) and bone resorption. Furthermore, it has been reported that weekly administration of PTH increases bone mass as much as every day administration of PTH, and as such, weekly administration of PTH has the potential to be a useful regimen with characteristics that are different from those of daily administration of PTH. PMID:17211094

  16. Detection of parathyroid hormone using an electrochemical impedance biosensor based on PAMAM dendrimers.

    PubMed

    Özcan, Hakk? Mevlüt; Sezgintürk, Mustafa Kemal

    2015-05-01

    This paper presents a novel hormone-based impedimetric biosensor to determine parathyroid hormone (PTH) level in serum for diagnosis and monitoring treatment of hyperparathyroidism, hypoparathyroidism and thyroid cancer. The interaction between PTH and the biosensor was investigated by an electrochemical method. The biosensor was based on the gold electrode modified by 12-mercapto dodecanoic (12MDDA). Antiparathyroid hormone (anti-PTH) was covalently immobilized on to poly amidoamine dendrimer (PAMAM) which was bound to a 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide/N-hydroxysuccinimide (EDC/NHS) couple, self-assembled monolayer structure from one of the other NH2 sites. The immobilization of anti-PTH was monitored by electrochemical impedance spectroscopy, cyclic voltammetry and scanning electron microscope techniques. After the optimization studies of immobilization materials such as 12MDDA, EDC-NHS, PAMAM, and glutaraldehyde, the performance of the biosensor was investigated in terms of linearity, sensitivity, repeatability, and reproducibility. PTH was detected within a linear range of 10-60 fg/mL. Finally the described biosensor was used to monitor PTH levels in artificial serum samples. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:815-822, 2015. PMID:25683333

  17. Serum ionized calcium, parathyroid hormone and related variables: effect of age and sex.

    PubMed

    Minisola, S; Pacitti, M T; Scarda, A; Rosso, R; Romagnoli, E; Carnevale, V; Scarnecchia, L; Mazzuoli, G F

    1993-12-01

    This study was carried out in order to determine interrelationships of age and sex on parameters within the parathyroid endocrine system in healthy men and women. One hundred and fifteen normal subjects (70 females and 45 males) subdivided into three groups aged 25-35, 45-55 and 65-75 years were studied. Female subjects aged between 45 and 55 were further subdivided into two age-matched groups in relation to gonadal functional status. Serum intact parathyroid hormone (PTH) concentrations were measured using a two-site immunoradiometric assay. We found that there was a significant decrease of serum ionized calcium with ageing only in men (r = -0.666, P < 0.001) and a significant increase of serum PTH with age in both men (r = 0.488, P < 0.001) and women (r = 0.279, P < 0.019). A significant inverse correlation was found between serum ionized calcium and PTH in male subjects (r = -0.661, P < 0.001) and in fertile females (r = -0.353, P < 0.037) but not in postmenopausal women or in the entire female population. Furthermore, we found a significant decline of serum phosphate (r = -0.484, P < 0.001) and TmP/GFR (r = -0.492, P < 0.001) with advancing age in men, but not in women. We believe that the decrease of serum ionized calcium, as a likely consequence of the physiological reduction of intestinal calcium absorption, is the pivotal factor responsible for the increased PTH levels we observed with advancing age. The phenomenon is clear in men and in premenopausal women, but is masked in the female sex at menopause by the effects of a shortage of oestrogen on the calcium-phosphorus metabolism. These may also be responsible for the differences observed between the two sexes as far as phosphate metabolism is concerned. In conclusion, this study has, for the first time, taken relationships between serum ionized calcium and PTH, over a wide age range, into consideration. The results obtained show a marked difference of serum ionized calcium values between sexes with ageing, while serum parathyroid hormone levels increase in both men and women. Important differences also exist, as far as phosphate metabolism is concerned, between males and females. PMID:8148663

  18. Parathyroid gland hormones in the skeletal development of the ovine foetus: the effect of parathyroidectomy with calcium and phosphate infusion.

    PubMed

    Aaron, J E; Abbas, S K; Colwell, A; Eastell, R; Oakley, B A; Russell, R G; Care, A D

    1992-02-01

    It has been confirmed that the foetal parathyroid glands are important in development and that thyroparathyroidectomy (TXPTX) of the ovine foetus with thyroxine (T4) replacement leads to hypocalcaemia, retarded skeletal development, depressed calcification and rickets, relative to thyroidectomy plus T4 replacement. Histomorphometric and biochemical (urinary excretion of deoxypyridinoline) indices of bone resorption are also reduced. However, skeletal calcification can be restored to normal by long-term infusion of the TXPTX foetuses with phosphate and calcium sufficient to normalise the plasma Ca2+ x Pi ion product. Nevertheless, depressed resorption, reduced osteoblast numbers and delayed development persisted. The evidence suggests that the abnormally low number of resorption cavities and osteoclasts may result from the reduction in circulatory parathyroid-hormone-related protein consequent upon the removal of the foetal parathyroid glands and that this hypercalcaemic factor has a direct effect upon the process of resorption and primary trabecular remodelling of the foetal skeleton. PMID:1576487

  19. Serum fat-soluble vitamin deficiency and abnormal calcium metabolism after malabsorptive bariatric surgery

    Microsoft Academic Search

    Slater GH; Siegel N; Williams T; Barr D; Wolfe B; Dolan K

    2004-01-01

    RESULTS: The incidence of vitamin A deficiency was 69%, vitamin K deficiency 68%, and vitamin D deficiency 63% by the fourth year after surgery. The incidence of vitamin E and zinc deficiency did not increase with time after surgery. The incidence of hypocalcemia increased from 15% to 48% over the study period with a corresponding increase in serum parathyroid hormone

  20. Structural Basis for Parathyroid Hormone-related Protein Binding to the Parathyroid Hormone Receptor and Design of Conformation-selective Peptides

    SciTech Connect

    Pioszak, Augen A.; Parker, Naomi R.; Gardella, Thomas J.; Xu, H. Eric; (Van Andel); (Mass. Gen. Hosp.)

    2009-12-01

    Parathyroid hormone (PTH) and PTH-related protein (PTHrP) are two related peptides that control calcium/phosphate homeostasis and bone development, respectively, through activation of the PTH/PTHrP receptor (PTH1R), a class B G protein-coupled receptor. Both peptides hold clinical interest for their capacities to stimulate bone formation. PTH and PTHrP display different selectivity for two distinct PTH1R conformations, but how their binding to the receptor differs is unclear. The high resolution crystal structure of PTHrP bound to the extracellular domain (ECD) of PTH1R reveals that PTHrP binds as an amphipathic {alpha}-helix to the same hydrophobic groove in the ECD as occupied by PTH, but in contrast to a straight, continuous PTH helix, the PTHrP helix is gently curved and C-terminally 'unwound.' The receptor accommodates the altered binding modes by shifting the side chain conformations of two residues within the binding groove: Leu-41 and Ile-115, the former acting as a rotamer toggle switch to accommodate PTH/PTHrP sequence divergence, and the latter adapting to the PTHrP curvature. Binding studies performed with PTH/PTHrP hybrid ligands having reciprocal exchanges of residues involved in different contacts confirmed functional consequences for the altered interactions and enabled the design of altered PTH and PTHrP peptides that adopt the ECD-binding mode of the opposite peptide. Hybrid peptides that bound the ECD poorly were selective for the G protein-coupled PTH1R conformation. These results establish a molecular model for better understanding of how two biologically distinct ligands can act through a single receptor and provide a template for designing better PTH/PTHrP therapeutics.

  1. Regulation of 1,25-dihydroxyvitamin D3 receptor gene expression by parathyroid hormone and cAMP-agonists.

    PubMed

    van Leeuwen, J P; Birkenhäger, J C; Vink-van Wijngaarden, T; van den Bemd, G J; Pols, H A

    1992-06-30

    We studied the effect of parathyroid hormone (PTH) and activation of the cAMP signal pathway on vitamin D receptor (VDR) mRNA levels in the phenotypically osteoblast cell line UMR 106. PTH caused a time- and dose-dependent increase of the VDR mRNA content with a maximum after 2 h. After 24 h the VDR mRNA level in PTH-treated cells returned to control level. In contrast, the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-induced increase in VDR mRNA did not decline after 24 h. Inhibition of transcription with actinomycin D (10 micrograms/ml) completely abolished the PTH-induced increase of VDR mRNA and inhibition of translation with cycloheximide (1 microgram/ml) resulted in superinduction of VDR mRNA. The role of cAMP in the induction of VDR mRNA was studied with several agents acting via the cAMP pathway. Incubation for 2 and 4 h with forskolin, Bt2cAMP, PTHrP or prostaglandin E2 caused an increase in the level of VDR mRNA comparable to that caused by PTH. The calcium ionophore A23187 did not affect VDR mRNA level. The present study demonstrates that PTH and activation of the cAMP signal pathway cause up-regulation of VDR via induction of VDR gene expression. The effect of cAMP on the VDR gene is suggestive for a cAMP responsive element in the VDR gene. PMID:1320878

  2. Original article Peculiarities of vitamin D and of the calcium

    E-print Network

    Paris-Sud XI, Université de

    Original article Peculiarities of vitamin D and of the calcium and phosphate homeostatic system in the horse. The con- centrations of Ca, Pi, vitamin D metabolites, parathyroid hormone (PTH), the activity of the alkaline phosphatase (AP) and the concentration and binding properties of vitamin D binding pro- tein (DBP

  3. Effect of parathyroid hormone on transport by toad and turtle bladder

    SciTech Connect

    Sabatini, S.; Kurtzman, N.A.

    1987-01-01

    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.

  4. Regional myocardial blood flow distribution during intracoronary infusion of parathyroid hormone

    SciTech Connect

    Crass, M.F. III; Lust, R.M.

    1986-03-01

    Although low doses of the biologically-active fragment of parathyroid hormone PTH-(1-34), have been shown to produce potent dilation of the coronary circulation specific regional and transmural (endo/epi) myocardial blood flow (MBF) responses to the hormone have not been described. Anesthetized open-chest mongrel dogs were instrumented to quantitate coronary blood flow and other cardiodynamic parameters. PTH-(1-34) was infused into the left circumflex artery (.008 nmol kg/sup -1/ min/sup -1/). Using the reference withdrawal method, radionuclide-labeled microspheres were injected before (basal flow), during (8 min after new steady-state flow), and after (restoration of basal flow) a 20 min infusion of PTH-(1-34). MFB increased from 76 +- 1.9 to 152 +- 3.5 ml min/sup -1/ 100 g/sup -1/ (P < .001) during PTH-(1-34) infusion. No differences in endo/epi flow ratio or regional coronary blood flow within the left ventricle were detected. Thus, in anesthetized dogs, the increase in MBF observed secondary to the PTH-(1-34)-induced decrease in coronary resistance appeared to be uniform transmurally and regionally, and is probably not the result of a shunting or steal phenomenon.

  5. Observations on the effect of parathyroid hormone on environmental blood lead concentrations in humans

    SciTech Connect

    Osterloh, J.D. (Univ. of California, San Francisco (USA))

    1991-02-01

    The effect of parathyroid hormone (PTH) on blood lead (Pb) concentrations was observed preliminarily in three different situations. Of 342 healthy bus drivers with no unusual exposure to Pb, 25 drivers with the highest and 25 with the lowest blood Pb were compared for serum PTH concentrations. There was no association between blood Pb and serum PTH concentrations. Eight women with postmenopausal osteoporosis enrolled in an experimental protocol to increase bone mass received daily PTH (1-34 fragment) for 1 week, calcitonin for the next 2 weeks, and oral calcium for the subsequent 10 weeks. This cycle was repeated four times during the year. Initial blood Pb concentrations averaged 6.0 micrograms/dl (range 2.1-8.9). Mean blood Pb concentrations decreased by 1.7 micrograms/dl over 1 year of therapy. The confidence interval for this change excluded zero, the mean change was significantly different from the mean change for comparative population (P less than 0.050), and paired changes were statistically significant (P = 0.045). Lastly, a single subject with hyperparathyroid disease and no unusual exposures to lead demonstrated stabilized blood Pb concentrations that were 50% lower after removal of his hyperplastic parathyroid glands. These observations suggest that the effect of PTH on increasing bone turnover and releasing Pb into blood is not easily detected at low physiologic amounts of PTH, but that with pathologic increases of PTH in hyperparathyroid disease, elevation of blood Pb from bone or increased gastrointestinal absorption may be possible. Likewise, either bone building therapies (PTH + calcitonin + calcium) may move Pb from blood into bone or supplemental calcium may decrease Pb gastrointestinal absorption, thereby explaining the observed lower blood Pb concentrations.

  6. The effects of parathyroid hormone and estradiol on cadmium accumulation by Madin-Darby canine kidney cells

    SciTech Connect

    Flanagan, J.L.

    1990-01-01

    Chronic exposure to the toxic metal cadmium causes osteomalacia, osteoporosis, increased serum parathyroid hormone, renal stone formation, hypercalciuria and renal tubular dysfunction, reflecting one or more disturbances of calcium homeostasis. Since renal cadmium (Cd[sup 2+]) transport proceeds in both proximal and distal tubules and parathyroid hormone (PTH) regulates calcium reabsorption at distal nephron sites, it was postulated that PTH may also stimulate Cd[sup 2+] transport in distal tubules. Madin-Darby canine kidney (MDCK) cells, which express a distal phenotype including PTH-sensitive adenylate cyclase and calcium transport, were used as the cell model for the present study. Cadmium uptake was measured using [[sup 109]Cd[sup 2+

  7. Hypercalcemia and parathyroid hormone-related peptide expression in a dog with thyroid carcinoma and histiocytic sarcoma.

    PubMed

    Scruggs, Jennifer L; Nobrega-Lee, Michelle; Fry, Michael M; Applegate, Rory

    2015-06-01

    A 9.5-year-old, male castrated Walker Hound was presented for evaluation of progressive weakness, anorexia, and weight loss. Imaging revealed multiple abdominal and thoracic masses and ascites; fine-needle aspirates of mesenteric and splenic masses confirmed malignancy, most likely histiocytic sarcoma. Laboratory analyses revealed increased ionized calcium and parathyroid hormone-related peptide (PTH-rP) concentrations, and concurrent low-normal parathyroid hormone concentration, consistent with humoral hypercalcemia of malignancy. Necropsy was performed after euthanasia. The dog had disseminated histiocytic sarcoma, including sarcomatosis, as well as bilateral thyroid carcinoma. PTH-rP immunostaining was positive in the thyroid carcinoma but negative in the histiocytic neoplasm. These results suggest that thyroid carcinoma-associated hypercalcemia can be caused by tumor secretion of PTH-rP. PMID:25707928

  8. Summer/winter differences in the serum 25-hydroxyvitamin D3 and parathyroid hormone levels of Japanese women

    NASA Astrophysics Data System (ADS)

    Nakamura, K.; Nashimoto, Mitsue; Yamamoto, Masaharu

    Serum 25-hydroxyvitamin D3 [25(OH)D3] is produced in the skin in response to exposure to ultraviolet radiation, and is a good indicator of vitamin D nutritional status. The aim of this study was to determine summer/winter differences in serum 25(OH)D3 and parathyroid hormone (PTH) in Japanese women and how the summer and winter values are related. The subjects were 122 healthy Japanese women aged 45-81 years (average age: 65.7 years). They were medically examined twice, in September 1997 and February 1999. Serum 25(OH)D3 and intact PTH were determined by high-performance liquid chromatography and a two-site immunoradiometric assay respectively. Lifestyle information was obtained through an interview. The seasonal differences (winter minus summer) in 25(OH)D3 [?25(OH)D3] and intact PTH concentrations were -18.8 nmol/l (SD 19.2, P<0.0001) and 0.98pmol/l (SD 1.02, P<0.0001) respectively. The correlation coefficient between summer (x) and winter (y) 25(OH)D3 levels was 0.462 (P<0.0001), with a linearly fitted line of y=0.42x+26.4. This relationship was interpreted as subjects with higher summer 25(OH)D3 values having greater reductions in winter 25(OH)D3 concentrations. There were inter-individual differences in ?25(OH)D3, although the summer and winter 25(OH)D3 concentrations were well-correlated. Since ?25(OH)D3 was not associated with any of the lifestyle factors, seasonal differences in the 25(OH)D3 concentrations of an individual appeared to reflect her ability to produce 25(OH)D3 photochemically in the skin. Sun bathing would be a less effective means of attaining adequate vitamin D nutritional status in a person with a small seasonal difference in 25(OH)D3, i.e., one with a low 25(OH)D3 level.

  9. Parathyroid hormone–related peptide (1 to 34) inhibits in vitro oxytocin-stimulated activity of pregnant baboon myometrium

    Microsoft Academic Search

    A. E. Pitera; G. C. S. Smith; R. A. Wentworth; P. W. Nathanielsz

    1998-01-01

    OBJECTIVES: We sought to determine the in vitro effect of parathyroid hormone–related protein fragment 1 to 34 on oxytocin precontracted myometrium from baboons in late gestation and to explore possible regional uterine differences in responsiveness comparing muscle strips from the lower uterine segment, posterior and anterior corpus, and fundus.STUDY DESIGN: We used cumulative concentration response (1 to 100 nmol\\/L) curves

  10. Pharmacodynamic Model of Parathyroid Hormone Modulation by a Negative Allosteric Modulator of the Calcium-Sensing Receptor

    Microsoft Academic Search

    Anson K. Abraham; Tristan S. Maurer; Amit S. Kalgutkar; Xiang Gao; Mei Li; David R. Healy; Donna N. Petersen; David A. Griffith; Donald E. Mager

    2011-01-01

    In this study, a pharmacodynamic model is developed, based on calcium–parathyroid hormone (PTH) homeostasis, which describes\\u000a the concentration–effect relationship of a negative allosteric modulator of the calcium-sensing receptor (CaR) in rats. Plasma\\u000a concentrations of drug and PTH were determined from plasma samples obtained via serial jugular vein sampling following single\\u000a subcutaneous doses of 1, 5, 45, and 150 mg\\/kg to male

  11. Regulation of Na + \\/H + exchange in opossum kidney cells by parathyroid hormone, cyclic AMP and phorbol esters

    Microsoft Academic Search

    Corinna Helmle-Kolb; Marshall Ho Montrose; Gerti Stange; Heini Murer

    1990-01-01

    Parathyroid hormone (PTH) controls two proximal tubular brush border membrane transport systems, Na+\\/phosphate co-transport and Na+\\/H+ exchange. In OK cells, a cell line with proximal tubular transport characteristics, PTH acts via kinase C and kinase A activation to inhibit Na+\\/phosphate co-transport [6, 8, 9, 19, 22]. In the present study, we show that PTH inhibits Na+\\/H+ exchange and that this

  12. Impact of Treatments for Postmenopausal Osteoporosis (Bisphosphonates, Parathyroid Hormone, Strontium Ranelate, and Denosumab) on Bone Quality: A Systematic Review

    Microsoft Academic Search

    S. J. Gallacher; T. Dixon

    2010-01-01

    The objective of this systematic review was to examine the influence of treatments for postmenopausal osteoporosis (parathyroid\\u000a hormone [PTH], bisphosphonates, strontium ranelate, and denosumab) on bone quality and discuss the clinical implications.\\u000a Most bone-quality data for PTH is from teriparatide. Teriparatide results in a rapid increase in bone-formation markers, followed\\u000a by increases in bone-resorption markers, opening an “anabolic window,” a

  13. Regulation of parathyroid hormone-related protein gene expression by epidermal growth factor-family ligands in primary human keratinocytes

    Microsoft Academic Search

    Yong-Mee Cho; Davina A Lewis; Peter F Koltz; Virgile Richard; Todd A Gocken; Thomas J Rosol; Raymond L Konger; Dan F Spandau; John Foley

    2004-01-01

    Cultured primary human keratinocytes were the first non-cancer-derived cell type reported to produce the humoral hypercalcemia factor, parathyroid hormone- related protein (PTHrP). Emerging evidence suggests that only a subset of keratinocytes produce high levels of PTHrP in vivo. We found that the PTHrP mRNA content of intact human skin was minimal, whereas transcripts were easily detectable in primary keratinocytes derived

  14. A non-(1- 84) circulating parathyroid hormone (PTH) fragment interferes significantly with intact PTH commercial assay measurements in uremic samples

    Microsoft Academic Search

    Raymond Lepage; Louise Roy; Jean-Hugues Brossard; Louise Rousseau; Claude Dorais; Claude Lazure; Pierre D'Amour

    We have previously shown that the Nichols assay for intact parathyroid hormone (I-PTH) reacts with a non- (1- 84) molecular form of PTH. This form behaves as a carboxy-terminal fragment and accumulates in renal failure, accounting for 40 - 60% of the measured immu- noreactivity. We wanted to see whether this was a common event with other commercial two-site I-PTH

  15. Influence of Glomerular Filtration Rate on Non(1-84) Parathyroid Hormone (PTH) Detected by Intact PTH Assays

    Microsoft Academic Search

    Jean-Hugues Brossard; Raymond Lepage; Heloise Cardinal; Louise Roy; Louise Rousseau; Claude Dorais; Pierre D'Amour

    Background: Commercial intact parathyroid hormone (I-PTH) assays detect molecular form(s) of human PTH, non-(1-84) PTH, different from the 84-amino acid native molecule. These molecular form(s) accumulate in hemo- dialyzed patients. We investigated the importance of non-(1-84) PTH in the interpretation of the increased I-PTH in progressive renal failure. Methods: Five groups were studied: 26 healthy individ- uals, 12 hemodialyzed patients,

  16. Thrombin and H64A subtilisin cleavage of fusion proteins for preparation of human recombinant parathyroid hormone

    Microsoft Academic Search

    Göran Forsberg; Michael Brobjer; Erik Holmgren; Katrin Bergdahl; Per Persson; Kaare M. Gautvik; Maris Hartmanis

    1991-01-01

    Human parathyroid hormone, hPTH, an 84 amino acid polypeptide, was produced intracellularly inEscherichia coli as a fusion protein, linked to the C-terminus of a 15 kD IgG-binding protein. Approximately 100 mg fusion protein was obtained per liter fermentation medium. To test the efficiency of two alternative enzymatic cleavage methods, two fusion proteins differing only in the linker region were constructed.

  17. Overexpression of Parathyroid Hormone-Related Protein in the Skin of Transgenic Mice Interferes with Hair Follicle Development

    Microsoft Academic Search

    John J. Wysolmerski; Arthur E. Broadus; Jing Zhou; Elaine Fuchs; Leonard M. Milstone; William M. Philbrick

    1994-01-01

    Parathyroid hormone-related peptide (PTHrP) was initially discovered as the cause of the syndrome of humoral hypercalcemia of malignancy. Subsequently, the PTHrP gene has been shown to be expressed in a wide variety of normal tissues, including skin. Because the biological function of PTHrP in skin remains unknown, we used the human keratin 14 promoter to target overexpression of PTHrP to

  18. Peripheral metabolism of PTH (parathyroid hormone): Fate of biologically active amino terminus in vivo

    SciTech Connect

    Bringhurst, R.R.; Stern, A.M.; Yotts, M.; Mizrahi, N.; Segre, G.V.; Potts, J.T. Jr. (Massachusetts General Hospital, Boston (USA))

    1988-12-01

    Clearance of intact parathyroid hormone (PTH) from blood is associated with rapid uptake by liver and kidney, limited proteolysis by tissue endopeptidases and, within minutes, appearance of circulating carboxyl-(COOH)-terminal PTH fragments. The fate of the corresponding amino(NH{sub 2})-terminal portion of the hormone during this peripheral metabolism is still unknown, however. To determine this, the authors have employed ({sup 35}S)bovine PTH (bPTH) labeled to high specific activity at NH{sub 2}-terminal methionines, which permits direct monitoring of the fate of the PTH NH{sub 2}-terminus during metabolism in vivo. The ({sup 35}S)PTH was administered by bolus or continuous intravenous infusion to anesthetized normal rats, to rats subjected to acute ablation of the liver, the kidneys, or both, and to rats receiving co-infusions of excess synthetic bPTH(1-34) NH{sub 2}-terminal fragments. Analysis by high-resolution chromatographic techniques sensitive to 10{sup {minus}13} M ({sup 35}S)PTH peptides in plasma yields no evidence that peripheral metabolism of PTH generates circulating NH{sub 2}-terminal fragments, even when special measures are taken to block clearance of such putative fragments from blood. They find that the NH{sub 2}-terminus of PTH is rapidly degraded in situ by the liver but that both liver and especially kidney nevertheless contain low levels of NH{sub 2}-terminal PTH fragments that, although not released into the blood, are large enough to be potentially active. Thus the peripheral metabolism of PTH in normal animals does not normally lead to the formation of circulating amino terminal fragments of the hormone that might act independently of intact PTH on peripheral target tissues.

  19. Serum 25-Hydroxyvitamin D and Parathyroid Hormone Levels in Non-Lactating Women with Post-Partum Thyroiditis: The Effect of l-Thyroxine Treatment.

    PubMed

    Krysiak, Robert; Kowalska, Beata; Okopien, Bogus?aw

    2015-06-01

    Vitamin D deficiency seems to be implicated in the onset and progression of some autoimmune disorders. No previous study has investigated vitamin D homeostasis in post-partum thyroiditis. We compared 25-hydroxyvitamin D and parathyroid hormone (PTH) levels between four groups of non-lactating women who gave birth within 12 months before the beginning of the study: hypothyroid women with post-partum thyroiditis (group A; n = 14), euthyroid females with post-partum thyroiditis (group B; n = 14), women with non-autoimmune hypothyroidism (group C; n = 16) and healthy euthyroid females without thyroid autoimmunity (group D; n = 15). In the second part of the study, groups A and C were treated for 6 months with l-thyroxine. Serum levels of 25-hydroxyvitamin D were lower, while PTH higher in patients with post-partum thyroiditis than in patients without thyroid autoimmunity. They were also lower (25-hydroxyvitamin D) or higher (PTH) in group A than in group B, as well as in group C in comparison with group D. l-thyroxine treatment increased 25-hydroxyvitamin D and reduced PTH levels only in hypothyroid women with post-partum thyroiditis. Baseline levels of 25-hydroxyvitamin D correlated with thyroid antibody titres, thyroid function and circulating PTH levels, while the effect of l-thyroxine on serum levels of this vitamin correlated with the changes in thyroid antibody titres and PTH levels. The results of our study suggest the association of vitamin D status with post-partum thyroiditis and l-thyroxine treatment of this disorder. PMID:25395280

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

    PubMed

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

    2014-04-01

    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

  1. PARATHYROID HORMONE RECEPTOR MEDIATES THE ANTI-MYELOMA EFFECT OF PROTEASOME INHIBITORS

    PubMed Central

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

    2014-01-01

    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

  2. Experimental and immunohistochemical studies on the possible role of parathyroid hormone in uraemic pruritus.

    PubMed

    Stĺhle-Bäckdahl, M; Hägermark, O; Lins, L E; Törring, O; Hilliges, M; Johansson, O

    1989-06-01

    Secondary hyperparathyroidism has been suggested as a cause of itching in chronic renal failure. The aim of the present study was to evaluate the possible role of parathyroid hormone (PTH) in pruritus affecting patients undergoing maintenance haemodialysis. In agreement with our previous findings, patients with pruritus had significantly (P less than 0.01) higher serum levels of PTH fragment 53-68 (m-PTH53-68) than patients without pruritus, 47.7 +/- 40.0 and 23.4 +/- 17.1 micrograms l-1 respectively. Serum concentrations of other substances including calcium, phosphate and magnesium did not differ between the two groups of patients. Intradermal injections of human PTH1-34 and PTH44-68 failed to evoke any acute or delayed cutaneous reactions in either patients or controls. Immunohistochemical investigations of skin biopsies from uraemic patients using several different antibodies against PTH were negative. Thus, the present results do not support PTH as a peripheral mediator of uraemic itching. PMID:2746157

  3. Role of Parathyroid Hormone-Related Protein Signaling in Chronic Pancreatitis

    PubMed Central

    Falzon, Miriam; Bhatia, Vandanajay

    2015-01-01

    Chronic pancreatitis (CP), a progressive inflammatory disease where acini are destroyed and replaced by fibrous tissue, increases the risk for pancreatic cancer. Risk factors include alcohol, smoking, and obesity. The effects of these risk factors are exacerbated in patients with mutations in genes that predispose to CP. The different environmental and genetic factors produce the same clinical phenotype; once CP develops, disease course is the same regardless of etiology. Critical questions still need to be answered to understand what modifies predisposition to develop CP in persons exposed to risk factors. We postulate that risk factors modulate endogenous pathways, with parathyroid hormone-related protein (PTHrP) signaling being one such pathway. In support, PTHrP levels are elevated in mice treated with alcohol, and in mouse models of cerulein- and pancreatic duct ligation-induced CP. Disrupting the Pthrp gene in acinar cells exerts protective effects (decreased edema, histological damage, amylase and cytokine release, and fibrosis) in these CP models. PTHrP levels are elevated in human CP. Currently, CP care lacks specific pharmacological interventions. Targeting PTHrP signaling may present a novel therapeutic strategy that inhibits pancreatic inflammation and fibrosis, especially since the risk of developing pancreatic cancer is strongly associated with duration of chronic inflammation. PMID:26095761

  4. Intact parathyroid hormone concentration and cyclic AMP metabolism in thyroid disease.

    PubMed

    Fraser, W D; Logue, F C; MacRitchie, K; Wilson, R M; Gray, H W; Beastall, G H; O'Reilly, D S

    1991-06-01

    In 35 thyrotoxic patients and 35 patients receiving thyroxine replacement therapy mean serum intact parathyroid hormone concentrations were lower than in euthyroid normal volunteer controls. In 20 hypothyroid patients intact PTH was increased relative to euthyroid controls. Mean serum adjusted calcium was increased in thyrotoxic patients relative to euthyroid controls and in 8 toxic patients with elevated serum adjusted calcium (greater than 2.60 mmol/l) intact PTH was below the assay detection limit (less than 0.5 pmol/l). Indices of PTH activity were consistent with intact PTH measurements in thyrotoxic patients with nephrogenous cyclic adenosine monophosphate lower, tubular maximum reabsorption of phosphate higher, and urinary calcium creatinine ratio higher than controls. In hypothyroid patients these indices of PTH activity suggest relative end organ resistance to PTH with nephrogenous cyclic adenosine monophosphate similar, tubular maximum reabsorption of phosphate similar, and calcium creatinine ratio lower than in controls. In treated hypothyroid patients nephrogenous cyclic adenosine monophosphate was higher, tubular maximum reabsorption of phosphate similar, and calcium creatinine ratio higher than in controls. These results are compatible with the hypothesis that thyroid status modifies the renal responses to PTH (1-84). PMID:1648852

  5. Role of Parathyroid Hormone-Related Protein Signaling in Chronic Pancreatitis.

    PubMed

    Falzon, Miriam; Bhatia, Vandanajay

    2015-01-01

    Chronic pancreatitis (CP), a progressive inflammatory disease where acini are destroyed and replaced by fibrous tissue, increases the risk for pancreatic cancer. Risk factors include alcohol, smoking, and obesity. The effects of these risk factors are exacerbated in patients with mutations in genes that predispose to CP. The different environmental and genetic factors produce the same clinical phenotype; once CP develops, disease course is the same regardless of etiology. Critical questions still need to be answered to understand what modifies predisposition to develop CP in persons exposed to risk factors. We postulate that risk factors modulate endogenous pathways, with parathyroid hormone-related protein (PTHrP) signaling being one such pathway. In support, PTHrP levels are elevated in mice treated with alcohol, and in mouse models of cerulein- and pancreatic duct ligation-induced CP. Disrupting the Pthrp gene in acinar cells exerts protective effects (decreased edema, histological damage, amylase and cytokine release, and fibrosis) in these CP models. PTHrP levels are elevated in human CP. Currently, CP care lacks specific pharmacological interventions. Targeting PTHrP signaling may present a novel therapeutic strategy that inhibits pancreatic inflammation and fibrosis, especially since the risk of developing pancreatic cancer is strongly associated with duration of chronic inflammation. PMID:26095761

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

    PubMed Central

    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

    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

  7. Proteoglycan 4, a novel immunomodulatory factor, regulates parathyroid hormone actions on hematopoietic cells.

    PubMed

    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

    2011-11-01

    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

  8. [Design and activity verification of human parathyroid hormone (1-34) mutant protein].

    PubMed

    Qiu, Shuang; Jiang, Yue-Shui; Li, Zhi-Qin; Lei, Jian-Yong; Chen, Yun; Jin, Jian

    2012-07-01

    Through protein-protein BLAST of homologous sequences in different species in NCBI database and preliminary simulating molecular docking and molecular dynamics by computer software discovery studio 3.1, three amino acids R25K26K27 of natural human parathyroid hormone (1-34) with Q25E26L27 were mutated and the biological activity of the mutant peptide was evaluated. Result showed that: root mean superposition deviation RMSD value between PTH (1-34)-(RKK-QEL) and PTH (1-34) peptide main chain was 2.509 3, indicating that the differences between the two main chain structural conformation was relatively small; the interaction energy between PTH (1-34)-(RKK-QEL) and its receptor protein PTH1R had been enhanced by 7.5% compared to nature PTH (1-34), from -554.083 kcal x mol(-1) to -599.253 kcal x mol(-1); the number of hydrogen bonds was increased from 32 to 38; PTH (1-34)-(RKK-QEL) can significantly stimulate the RANKL gene expression (P < 0.01) while inhibiting the OPG gene expression (P < 0.01) in UAMS-32P cells; in the co-culture system of UAMS-32P cells and mouse primary femur bone marrow cells, PTH (1-34)-(RKK-QEL) stimulated the formation of osteoclasts (P < 0.01) and had a higher biological activity than PTH (1-34) standard reagents. PMID:22993856

  9. Effect of parathyroid hormone and calcitonin on acetylcholine release in rat sympathetic superior cervical ganglion.

    PubMed

    Stern, J E; Cardinali, D P

    1994-07-11

    The effects of parathyroid hormone (PTH) and calcitonin on acetylcholine release by rat superior cervical ganglion (SCG) were evaluated in vitro. SCG labeled with [3H]choline were exposed to four 5 min-long pulses of 40 mM K+, 35 min apart. PTH increased, and calcitonin inhibited, in a dose-dependent way, K(+)-elicited [3H]acetylcholine release, with apparent effective doses 50 of about 10(-9) M. The effect of PTH was inhibited by co-incubation with the PTH receptor antagonist NLe [8-18]-PTH (3-34) amide. Incubation of SCG for 120 min with PTH or calcitonin resulted in dose-dependent augmentation or inhibition of K(+)-induced increase of high affinity [3H]choline uptake, respectively, with a maximal effect at 10(-8) M concentration (PTH) and 10(-9) M concentration (calcitonin) and declining at higher concentrations. The increase in SCG [3H]choline uptake induced by PTH was blunted by preincubation with the PTH antagonist NLe [8-18]-PTH (3-34) amide. At 10(-7) M concentrations, PTH increased significantly the in vitro conversion of [3H]choline to [3H]acetylcholine, an effect inhibited by PTH receptor antagonist. Calcitonin did not modify SCG [3H]acetylcholine synthesis by rat SCG. The results indicate that, in vitro, PTH increases, and calcitonin inhibits, acetylcholine release in rat SCG. PMID:7953692

  10. Specific inhibition of long-lasting, L-type calcium channels by synthetic parathyroid hormone

    SciTech Connect

    Pang, P.K.T.; Wang, R.; Shan, J.; Karpinski, E.; Benishin, C.G. (Univ. of Alberta, Edmonton (Canada))

    1990-01-01

    The effect of an active synthetic N-terminal fragment of bovine parathyroid hormone (bPTH), bPTH-(1-34), on Ca{sup 2+} channels was studied in mouse neuroblastoma cells (N1E-115). With the whole-cell variation of the patch-clamp technique, T (transient) and L (long-lasting) types of Ca{sup 2+} currents were identified. Pharmacological characterization showed that the L current was amplified by the Ca{sup 2+} channel stimulator BAY K-8644, but the T current was unaffected. The administration of bPTH-(1-34) produced dose-related inhibition of the L current, which could be reversed by BAY K-8644. The peptide had no effect on the T current. In addition, use of the fluorescent indicator fura-2 showed that bPTH-(1-34) inhibited the KCl-stimulated increase in intracellular free Ca{sup 2+} in neuroblastoma cells with L channels but not in cells with T channels. An inactivated (oxidized) preparation of bPTH-(1-34) failed to affect the L current. High-affinity binding of labeled PTH analog to these neuroblastoma cells was also demonstrated. In addition, bPTH-(1-34) inhibited the L current in cultured vascular smooth muscle cells from rat tail artery. These data indicate that, in some tissues PTH can act as an endogenous blocker of Ca{sup 2+} entry.

  11. Selective Uptake of the Synthetic Amino Terminal Fragment of Bovine Parathyroid Hormone by Isolated Perfused Bone

    PubMed Central

    Martin, Kevin J.; Freitag, Jeffrey J.; Conrades, Mary B.; Hruska, Keith A.; Klahr, Saulo; Slatopolsky, Eduardo

    1978-01-01

    Studies from our laboratory have shown that the metabolic clearance rate of carboxy terminal immunoreactive parathyroid hormone (i-PTH) can be accounted for by extraction of i-PTH by liver and kidney. In contrast, there was no demonstrable hepatic uptake of the synthetic amino terminal bovine PTH fragment (syn b-PTH 1-34) and the kidney accounted for only 45% of the metabolic clearance rate of amino terminal i-PTH. This suggested that another major site, presumably bone, played a role in the metabolism of syn b-PTH 1-34. Extraction of i-PTH by isolated perfused bone was studied during infusion of purified bovine PTH (b-PTH) 1-84 or syn b-PTH 1-34. In five studies during infusion of syn b-PTH 1-34 the arteriovenous difference for i-PTH across bone was 36%. In contrast, no significant uptake of carboxy terminal i-PTH was observed in nine studies during infusion of b-PTH 1-84. In addition, when H2O2-oxidized (biologically inactive) syn b-PTH 1-34 was used no arteriovenous difference was observed. These findings correlated with the ability of these PTH preparations to stimulate cyclic AMP production by the perfused bone. Syn b-PTH 1-34 increased cyclic AMP production at perfusate PTH concentrations of 1-5 ng/ml, whereas b-PTH 1-84 evoked only a minimal response at concentrations of 10-20 ng/ml. We conclude that bone is a major site of metabolism of the amino terminal PTH fragment, syn b-PTH 1-34. In addition, these data suggest that cleavage of the intact hormone, with the production of amino terminal PTH fragments by peripheral organs (liver and kidney), may play a major role in the regulation of PTH effects on bone. PMID:209059

  12. Bovine parathyroid hormone-(41-84), a hormone fragment with desirable properties for use as radioligand

    SciTech Connect

    Mallette, L.E.; Bradley, W.A.

    1981-12-01

    Radioiodinated bPTH has been widely used as the labeled ligand in the radioimmunoassay of PTH. We now report the properties of a carboxyterminal fragment of bPTH that has several favorable characteristics when used as radioligand. This peptide, the chief component of a commercial preparation of bPTH, was isolated by gel filtration, where it migrated more slowly than did authentic bPTH-(1-84). It yielded lower nonspecific binding values and more sensitive hPTH assays than were seen with the intact hormone. By immunological criteria this peptide lacked the aminoterminal region of PTH, since hPTH-(1-34) did not inhibit its binding to any of 11 different antisera with known ability to recognize the aminoterminal region of PTH. The peptide did not contain most or all of the carboxyterminal region, however, since its binding to anti-PTH sera was inhibited by hPTH-(44-68) or hPTH-(53-84). Sequential Edman degradation of the iodinated peptide released iodotyrosine at the third cycle, suggesting the structure, bPTH-(41-84). The lower nonspecific binding and enhanced assay sensitivity provided by this peptide suggest that the use of other natural or synthetic fragments of PTH as radioligands might enhance the performance of PTH assays.

  13. Parathyroid hormone-dependent signaling pathways regulating genes in bone cells

    NASA Technical Reports Server (NTRS)

    Swarthout, John T.; D'Alonzo, Richard C.; Selvamurugan, Nagarajan; Partridge, Nicola C.

    2002-01-01

    Parathyroid hormone (PTH) is an 84-amino-acid polypeptide hormone functioning as a major mediator of bone remodeling and as an essential regulator of calcium homeostasis. PTH and PTH-related protein (PTHrP) indirectly activate osteoclasts resulting in increased bone resorption. During this process, PTH changes the phenotype of the osteoblast from a cell involved in bone formation to one directing bone resorption. In addition to these catabolic effects, PTH has been demonstrated to be an anabolic factor in skeletal tissue and in vitro. As a result, PTH has potential medical application to the treatment of osteoporosis, since intermittent administration of PTH stimulates bone formation. Activation of osteoblasts by PTH results in expression of genes important for the degradation of the extracellular matrix, production of growth factors, and stimulation and recruitment of osteoclasts. The ability of PTH to drive changes in gene expression is dependent upon activation of transcription factors such as the activator protein-1 family, RUNX2, and cAMP response element binding protein (CREB). Much of the regulation of these processes by PTH is protein kinase A (PKA)-dependent. However, while PKA is linked to many of the changes in gene expression directed by PTH, PKA activation has been shown to inhibit mitogen-activated protein kinase (MAPK) and proliferation of osteoblasts. It is now known that stimulation of MAPK and proliferation by PTH at low concentrations is protein kinase C (PKC)-dependent in both osteoblastic and kidney cells. Furthermore, PTH has been demonstrated to regulate components of the cell cycle. However, whether this regulation requires PKC and/or extracellular signal-regulated kinases or whether PTH is able to stimulate other components of the cell cycle is unknown. It is possible that stimulation of this signaling pathway by PTH mediates a unique pattern of gene expression resulting in proliferation in osteoblastic and kidney cells; however, specific examples of this are still unknown. This review will focus on what is known about PTH-mediated cell signaling, and discuss the established or putative PTH-regulated pattern of gene expression in osteoblastic cells following treatment with catabolic (high) or anabolic (low) concentrations of the hormone.

  14. About the Parathyroid Glands

    MedlinePLUS

    ... hormoneparathyroid hormone (PTH). This sets off a chain of events that get more calcium into the ... call. Interestingly, and perhaps surprising to most, this chain of events happens without us knowing about or ...

  15. Serum 25-hydroxyvitamin D and parathyroid hormone in patients with ankylosing spondylitis before and after a three-week rehabilitation treatment at high altitude during winter and spring.

    PubMed

    Falkenbach, A; Tripathi, R; Sedlmeyer, A; Staudinger, M; Herold, M

    2001-04-30

    Does a sojourn at high altitude during the winter and spring improve vitamin D status (and possibly suppress parathyroid hormone [PTH]) in patients with ankylosing spondylitis (AS)? In 73 patients with AS, serum concentrations of 25-hydroxy-vitamin D [25(OH)D] and PTH were determined before and after a three-week rehabilitation treatment at Bad Gastein (1000 m above sea level). At the first examination, serum 25(OH)D was median (25th, 75th percentile) 15.5 ng mL-1 (10.0 ng mL-1, 20.6 ng mL-1). Thirteen patients (18%) had a 25(OH)D concentration below 8 ng mL-1. In 53 patients (73%) the level was below 20 ng mL-1. After the sojourn, 25(OH)D significantly (p = 0.02) increased to 19.7 (11.3, 24.6) ng mL-1. PTH did not change significantly, being 32 (22.4, 43.9) pg mL-1 before and 30.3 (24.1, 39.9) pg mL-1 after the sojourn. Analysing different periods of sojourn, a significant (p < 0.001) increase in 25(OH)D was found in April but not in the other months. Patients with ankylosing spondylitis may have extremely low levels of 25(OH)D. The results of the present study suggest that a sojourn at high altitude in early spring is liable to reduce vitamin D deficiency. PMID:11388078

  16. Evidence for coordinated regulation of osteoblast function by 1,25-dihydroxyvitamin D3 and parathyroid hormone.

    PubMed

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

    1996-06-01

    From several animal studies and clinical observations it became evident that at target tissue level 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and parathyroid hormone (PTH) must act in an interrelated manner. In the present study we examined the interaction between 1,25-(OH)2D3 and PTH in the target cell of these hormones in bone, the osteoblast. In addition we studied the role of PTH-activated signal pathways. The three osteoblastic cell lines UMR 106, ROS 17/2.8 and MG-63 were used as model systems. In UMR 106 cells 1,25-(OH)2D3 and PTH caused a synergistic up-regulation of the vitamin D receptor (VDR) which was accompanied by a synergistic induction of VDR mRNA expression whereas in both ROS 17/2.8 and MG-63 cells no interaction was observed. In UMR 106 cells the effect of PTH on homologous up-regulation of VDR could be mimicked by the cAMP agonist forskolin and by dibutyrylic-cAMP. Phorbol ester activation of protein kinase C reduced basal as well as 1,25-(OH)2D3-induced up-regulation of VDR. 1,25-(OH)2D3 induced 24-hydroxylase activity in UMR 106 and MG 63 cells and, in contrast to VDR regulation, in both cell lines PTH and 1,25-(OH)2D3 synergistically induce 24-hydroxylase activity. Similar to VDR regulation the effect of PTH was mimicked by activation of cAMP production whereas protein kinase C activation reduced the induction by 1,25-(OH)2D3. Finally, we examined the interaction with respect to osteocalcin synthesis. In ROS 17/2.8 and MG-63 cells 1,25-(OH)2D3 stimulated osteocalcin production. In ROS 17/2.8 cells PTH as well as stimulation of cAMP production by forskolin enhanced 1,25-(OH)2D3-induced osteocalcin production whereas, as we have shown previously, activation of protein kinase C does not change 1,25-(OH)2D3-stimulated osteocalcin production. In MG-63 cells neither PTH nor forskolin significantly changed 1,25-(OH)2D3 induction of osteocalcin synthesis. From the present study it can be concluded that indeed at target cell level 1,25-(OH)2D3 and PTH act in a coordinated manner. On basis of the potentiation of 1,25-(OH)2D3 action by PTH in osteoblasts together with the previously reported inhibition of PTH-stimulated cAMP production by 1,25-(OH)2D3 we postulate a negative feedback-loop at target cell level. The activation of the cAMP pathway results in an enhancement of the 1,25-(OH)2D3 action whereas the protein kinase C pathway attenuates the 1,25-(OH)2D3 action. Finally, the present study provides a basis for the indications from in vivo observations about an interrelated action of 1,25-(OH)2D3 and PTH at the target cell. More generally it demonstrates on the basis of analyses of endogenous cellular responses evidence for an interplay between receptor-activated pathways of peptide and steroid hormones. PMID:8679716

  17. Low Dose Parathyroid Hormone Maintains Normal Bone Formation in Adult Male Rats During Rapid Weight Loss

    PubMed Central

    Turner, Russell T.; Iwaniec, Urszula T.

    2011-01-01

    A persistent negative energy balance results in bone loss. It is not clear whether the bone loss associated with chronic negative energy balance can be prevented. The objective of this study was to assess the efficacy of intermittent low dose parathyroid hormone (PTH) treatment in maintaining normal bone formation during severe energy restriction. Six-month-old male Fisher 344 rats were divided into 4 treatment groups: (1) baseline, (2) ad libitum (ad lib)-fed control, (3) energy-restricted (to consume 40% ad lib caloric intake), or (4) energy-restricted + low dose (1 ?g/kg/d) PTH. Severe energy restriction for 14 days decreased body weight and serum leptin levels. Compared to ad lib-fed controls, energy-restricted rats had lower cancellous bone formation, higher osteoclast perimeter/bone perimeter and higher bone marrow adiposity in the proximal tibial metaphysis. Also, the energy-restricted rats had a lower periosteal bone formation rate at the tibia-fibula synostosis. Administration of PTH to energy-restricted rats had no effect on weight loss or osteoclast perimeter/bone perimeter. In contrast, energy-restricted rats treated with PTH had higher rates of cancellous and cortical bone formation compared to energy-restricted rats, and did not differ from the ad lib-fed control animals. Furthermore, PTH treatment maintained normal bone marrow adiposity. In conclusion, rapid weight loss in adult male rats was accompanied by decreased bone formation and increased bone marrow adiposity and these changes were prevented by low dose PTH treatment. Taken together, the results suggest that the energy cost of bone formation in adult rats is low and PTH therapy is effective in preventing the reduced bone formation associated with rapid weight loss. PMID:21215827

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

    PubMed Central

    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

    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

  19. Inhibition of carbonic anhydrase by parathyroid hormone and cyclic AMP in rat renal cortex in vitro.

    PubMed Central

    Beck, N; Kim, K S; Wolak, M; Davis, B B

    1975-01-01

    It has been demonstrated that parathyroid hormone (PTH) inhibits the proximal tubular reabsorption of bicarbonate, and increases the urinary excretion of that ion. There is also a qualitative similarity between the alterations of the proximal tubular reabsorption of phosphate, sodium, and water after PTH administration and after acetazolamide administration. These findings suggest that the renal effect of PTH is possibly mediated through the inhibition of carbonic anhydrase in proximal tubules. Therefore, a possible inhibitory effect of PTH on carbonic anhydrase was evaluated in the homogenate of rat renal cortex by an indicator titration method. Incubation of cortical homogenates with PTH for 10 min at 37degreesC inhibited carbonic anhydrase activity. The inhibitory effect of PTH was ATP-, Mg++-, and K+-dependent and temperature-dependent; inactivation of PTH by heating at 100degreesC abolished the effect of PTH both to activate adenylate cyclase and to inhibit carbonic anhydrase. Calcium 5 mM also partially abolished effects of PTH to activate adenylate cyclase and to inhibit carbonic anhydrase. The inhibitory effect of PTH on carbonic anhydrase was specific to renal cortex. Cyclic AMP, the intracellular messenger substance for PTH, also inhibited carbonic anhydrase in renal cortex. The cyclic AMP-induced inhibition was also Mg++ dependent and temperature dependent, and required preincubation at 37degreesC. But 5'-AMP, a metabolic derivative of cyclic AMP without its biological effect, had no inhibitory effect on carbonic anhydrase. All the above results are consistent with the hypothesis that PTH inhibits proximal tubular reabsorption of bicarbonate and phosphate through the inhibition of carbonic anhydrase, and that inhibitory effect is mediated through the cyclic AMP system. PMID:233968

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

    PubMed Central

    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

    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

  1. Proteoglycan 4: a dynamic regulator of skeletogenesis and parathyroid hormone skeletal anabolism.

    PubMed

    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

    2012-01-01

    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

  2. Nuclear localization of parathyroid hormone-related peptide confers resistance to anoikis in prostate cancer cells

    PubMed Central

    Park, Serk In; McCauley, Laurie K

    2013-01-01

    Prostate cancer remains a leading cause of cancer-related death in men, largely attributable to distant metastases, most frequently to bones. Despite intensive investigations, molecular mechanisms underlying metastasis are not completely understood. Among prostate cancer-derived factors, parathyroid hormone-related peptide (PTHrP), first discovered as an etiologic factor for malignancy-induced hypercalcemia, regulates many cellular functions critical to tumor growth, angiogenesis, and metastasis. In this study, the role of PTHrP in tumor cell survival from detachment-induced apoptosis (i.e. anoikis) was investigated. Reduction of PTHLH (encoding PTHrP) gene expression in human prostate cancer cells (PC-3) increased the percentage of apoptotic cells when cultured in suspension. Conversely, overexpression of PTHrP protected prostate cancer cells (Ace-1 and LNCaP, both typically expressing low or undetectable basal PTHrP) from anoikis. Overexpression of nuclear localization signal (NLS)-defective PTHrP failed to protect cells from anoikis, suggesting that PTHrP-dependent protection from anoikis is an intracrine event. A PCR-based apoptosis-related gene array showed that detachment increased expression of the TNF gene (encoding the proapoptotic protein tumor necrosis factor-?) fourfold greater in PTHrP-knockdown PC-3 cells than in control PC-3 cells. In parallel, TNF gene expression was significantly reduced in PTHrP-overexpressing LNCaP cells, but not in NLS-defective PTHrP overexpressing LNCaP cells, when compared with control LNCaP cells. Subsequently, in a prostate cancer skeletal metastasis mouse model, PTHrP-knockdown PC-3 cells resulted in significantly fewer metastatic lesions compared to control PC-3 cells, suggesting that PTHrP mediated antianoikis events in the bloodstream. In conclusion, nuclear localization of PTHrP confers prostate cancer cell resistance to anoikis, potentially contributing to prostate cancer metastasis. PMID:22291434

  3. A potential therapeutic approach to overload-induced bone loss around implant: parathyroid hormone (PTH).

    PubMed

    Zeng, Xiaohua; He, Hao; Zhang, Liang; Wu, Yingying; Wang, Yanying; Gong, Ping

    2011-11-01

    The clinical use of dental implants has a high success rate, but overload-induced bone loss around implant is not uncommon in patients with implant-supported denture especially those with long cantilever designs and greatly harmful to the long-term implant success. The mechanism underlying the bone loss is thought to be the imbalance of bone remodeling involving a detrimental positive feedback activated by overloading. While surgical regenerative treatments may be useful in promoting bone regeneration, extra suffering and risk of infection have to be fully recognized. To date, no optimal method is available to solve this problem. We hereby propose a novel therapy that may potentially improve this condition. Many studies have shown that parathyroid hormone (PTH), an anabolic agent targeting bone, is effective in reversing bone loss caused by osteoporosis with negative bone remodeling in clinical studies. Moreover, PTH has the potential to accelerate the bone healing in patients with fracture and fracture nonunion and improve osseointegration of implant inserted in pre-existed bone defect via its anabolic effect to increase bone formation in animal model studies. Specifically for alveolar bone, PTH is associated with effective bone regeneration in patients with severe periodontitis. What is more, PTH and mechanical loading has a synergistic effect on bone formation, which is in favor of bone healing under physiological loading. The mechanisms underlying its anabolic effect may involve increased osteoblasts activity, prolonged osteoblasts life-span and recruitment of new osteoblasts from marrow stromal cells. Furthermore, PTH could activate resting lining cells to initial de novo bone formation. Considering these actions of PTH, we hypothesize that PTH may be a potential treatment for overload-induced bone loss around implant. PMID:21908105

  4. PTH (parathyroid hormone) elevates inositol polyphosphates and diacylglycerol in a rat osteoblast-like cell line

    SciTech Connect

    Civitelli, R.; Reid, I.R.; Westbrook, S.; Avioli, L.V.; Hruska, K.A. (Jewish Hospital of St. Louis, MO (USA))

    1988-11-01

    Parathyroid hormone (PTH)-stimulated signal transduction through mechanisms alternate to adenosine 3{prime},5{prime}-cyclic monophosphate (cAMP) production were studied in UMR 106-01 cells, a cell line with an osteoblastic phenotype. PTH produced transient, dose-related increases in cytosolic calcium ((Ca{sup 2+}){sub i}), inositol trisphosphates, and diacylglycerol (DAG). Both inositol 1,4,5-trisphosphate (Ins-1,4,5P{sub 3}) and inositol 1,3,4-trisphosphate (Ins-1,3,4P{sub 3}) production were rapidly stimulated by PTH. Consistent with the production of Ins-1,3,4P{sub 3}, rapid stimulation of late eluting inositol tetrakisphosphate was observed. The effects on the inositol phosphates were induced rapidly, consistent with roles as signals for changes in (Ca{sup 2+}){sub i}. In saponin-permeabilized UMR 106-01 cells, Ins-1,4,5P{sub 3} stimulated {sup 45}Ca release from a nonmitochondrial intracellular pool. Thus the hypothesis that PTH-stimulated Ins-1,4,5P{sub 3} production initiates Ca{sup 2+} release and contributes to transient elevations of (Ca{sup 2+}){sub i} is supported. These data suggest that stimulation of cAMP production during PTH stimulation may negatively affect production of rises in (Ca{sup 2+}){sub i} during PTH stimulation. The inactivation of the inhibitory G protein of adenylate cyclase by pertussis toxin could explain its action similar to cAMP analogues. Cyclci nucleotides diminish the effects of PTH on (Ca{sup 2+}){sub i}, probably interacting on a biochemical step subsequent to or independent of Ins-1,4,5P{sub 3} release.

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

    SciTech Connect

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

    1985-05-01

    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.

  6. Parathyroid hormone suppression by intravenous 1,25-dihydroxyvitamin D. A role for increased sensitivity to calcium.

    PubMed Central

    Delmez, J A; Tindira, C; Grooms, P; Dusso, A; Windus, D W; Slatopolsky, E

    1989-01-01

    Numerous in vitro studies in experimental animals have demonstrated a direct suppressive effect of 1,25-dihydroxyvitamin D (1,25(OH)2D) on parathyroid hormone (PTH) synthesis. We therefore sought to determine whether such an effect could be demonstrated in uremic patients undergoing maneuvers designed to avoid changes in serum calcium concentrations. In addition, the response of the parathyroid gland in patients undergoing hypercalcemic suppression (protocol I) and hypocalcemic stimulation (protocol II) before and after 2 wk of intravenous 1,25(OH)2D was evaluated. In those enlisted in protocol I, PTH values fell from 375 +/- 66 to 294 +/- 50 pg (P less than 0.01) after 1,25(OH)2D administration. During hypercalcemic suppression, the "set point" (PTH max + PTH min/2) for PTH suppression by calcium fell from 5.24 +/- 0.14 to 5.06 +/- 0.15 mg/dl (P less than 0.05) with 1,25(OH)2D. A similar decline in PTH levels after giving intravenous 1,25(OH)2D was noted in protocol II patients. During hypocalcemic stimulation, the parathyroid response was attenuated by 1,25(OH)2D. We conclude that intravenous 1,25(OH)2D directly suppresses PTH secretion in uremic patients. This suppression, in part, appears to be due to increased sensitivity of the gland to ambient calcium levels. PMID:2703535

  7. Metabolism and Action of the Hormone Vitamin D

    PubMed Central

    Coburn, Jack W.; Hartenbower, David L.; Norman, Anthony W.

    1974-01-01

    Extensive experimental evidence has established a significant role of calciferol in the maintenance of normal calcium homeostasis. Present knowledge indicates that vitamin D3 must first be converted to 25-OH-D3 and then to 1,25(OH)2D3, the most active known form of the steroid. Many of the factors regulating the rate of production of this last steroid from its precurser have been evaluated, and the concept that vitamin D functions as a steroid hormone seems to be well established. Deranged action of calciferol, caused by impaired metabolism of the steroid or through altered sensitivity of target tissues, may be involved in the pathophysiology of several disease states with abnormal calcium metabolism. It is noted that liver disease, osteomalacia due to anticonvulsant therapy, chronic renal failure, hypophosphatemic rickets, hypoparathyroidism, hyperparathyroidism, sarcoidosis and idiopathic hypercalciuria have possible relation to alterations in metabolism or action of vitamin D. The future clinical availability of 1,25(OH)2D3 and other analogs of this steroid may offer potential therapeutic benefit in the treatment of certain of the disease entities discussed. PMID:4365934

  8. Vitamin D Deficiency in the Absence of Enteropathy in Three Cases with Common Variable Immunodeficiency

    Microsoft Academic Search

    Ömür Ardeniz; Aytul Sin; Gökhan Özgen; Fulya Gunsar; Nihal Mete; Okan Gulbahar; Ali Kokuludag

    2008-01-01

    Background: Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and a defect in antibody production. Herein we describe 3 patients diagnosed with CVID in whom vitamin D deficiency was detected in the absence of enteropathy. Methods: Biochemical and immunological analysis, serum osteocalcin, parathyroid hormone, 25-OH vitamin D, 1,25(OH)2 vitamin D, vitamin A, vitamin E, urinary calcium, and deoxypyridinoline measurements were

  9. The association between parathyroid hormone and mortality in dialysis patients is modified by wasting

    PubMed Central

    Drechsler, Christiane; Krane, Vera; Grootendorst, Diana C; Ritz, Eberhard; Winkler, Karl; März, Winfried; Dekker, Friedo; Wanner, Christoph

    2009-01-01

    Background. The association between parathyroid hormone (PTH) level and mortality in dialysis patients is controversial. We hypothesized that wasting, a common condition potentially related to adynamic bone disease, modifies the association of PTH with mortality and cardiovascular events (CVE), respectively. Methods. We analysed data from 1255 diabetic haemodialysis patients, participating in the German Diabetes and Dialysis Study between 1998 and 2004. The patients were stratified by the presence or absence of wasting (albumin ?3.8 versus albumin >3.8 g/dL; BMI ?23 versus BMI >23 kg/m2). Using Cox regression analyses, we calculated the risks of (1) all-cause mortality and (2) CVE according to baseline PTH levels. All analyses were adjusted for age, sex, atorvastatin treatment, duration of dialysis, comorbidity, HbA1c, phosphate, calcium, blood pressure, haemoglobin and C-reactive protein. Results. Patients had a mean age of 66 ± 8 years, and 54% were male. Among patients without wasting (albumin >3.8 g/dL, n = 586), the risks of death and CVE during 4 years of follow-up significantly increased by 23% and 20% per unit increase in logPTH. Patients in the highest PTH tertile had a 74% higher risk of death (HRadj 1.74, 95% CI 1.27–2.40) and a 49% higher risk of CVE (HRadj 1.49, 95% CI 1.05–2.11) compared to patients in the lowest PTH tertile. In contrast, no effect was found in patients with wasting. Accordingly, additional analyses in strata of BMI showed that PTH significantly impacted on death and CVE [HR(logPTH)adj 1.15 and 1.14, respectively] only in patients without, but not in patients with, wasting. Conclusions. Wasting modifies the association of PTH with adverse outcomes in diabetic dialysis patients. High PTH levels are of concern in the patients without wasting, while the effect of PTH on mortality is nullified in the patients with wasting. PMID:19474272

  10. Abnormalities in hepatic lipase in chronic renal failure: role of excess parathyroid hormone.

    PubMed Central

    Klin, M; Smogorzewski, M; Ni, Z; Zhang, G; Massry, S G

    1996-01-01

    Post-heparin hepatic lipase activity is reduced in chronic renal failure (CRF). This could be due to reduced synthesis, decreased activity, and/or impaired secretion of the enzyme. Further, the factor(s) responsible for such derangements are not elucidated. We examined hepatic lipase metabolism in normal, 6-wk-old CRF rats, CRF-PTX (parathyroidectomized) rats, and CRF and normal rats treated with verapamil (CRF-V, normal-V) using liver homogenate, hepatic cell culture for 8 h, and in vitro liver perfusion. The Vmax of hepatic lipase in liver homogenate was significantly (P < 0.01) reduced and the Km was significantly (P < 0.01) increased in CRF rats, but the values were normal in CRF-PTX, CRF-V, and normal-V rats. Culture of hepatic cells for 8 h was associated with an increase in hepatic lipase activity but the increment in CRF rats was significantly (P < 0.01) lower than that of normal, CRF-PTX, CRF-V, and normal-V rats. Both parathyroid hormone (PTH)-(1-84) and 1-34 inhibited the production of hepatic lipase in cultured cells from normal, CRF-PTX, CRF-V, and normal-V rats. The expression of the mRNA of the hepatic lipase was significantly reduced in CRF animals with the ratio between it and that of house keeping gene G3DPH being 15 +/-3% compared to 40 +/- 1.3% in normal, 44+/-2.9% CRF-PTX, 44 +/- 5.4% in CRF-V, and 39 +/- 3.9% in normal-V rats. Infusion of heparin to the in vitro hepatic perfusion system increased the activity of hepatic lipase in the effluent in all groups of rat except in CRF animals. Infusion of PTH-(1-34) in dose of 10(-6) M into the liver perfusion system inhibited the increase in post-heparin hepatic lipase activity. The data show that in CRF (a) the mRNA of hepatic lipase is downregulated, and hepatic lipase production, activity and release are impaired, (b) that this is due to the state of secondary hyperparathyroidism of CRF since both acute and chronic excess of PTH were associated with these abnormalities, (c) and that prevention of excess PTH by PTX of CRF rats or blocking the effect of PTH by treatment with verapamil corrected the derangement in hepatic lipase metabolism. PMID:8636395

  11. Intermittent parathyroid hormone treatment can promote linear growth in the ovariectomized growing rat.

    PubMed

    Lim, S K; Won, Y J; Park, D H; Shin, D H; Yook, J I; Lee, H C; Huh, K B

    1999-04-01

    To compare the effect of intermittent parathyroid hormone (PTH) treatment with that of estrogen treatment on epiphyseal growth in ovariectomized rats, 46 Sprague-Dawley female rats aged 9-10 weeks (about 200-220 g) were either ovariectomized or sham operated. From 6 weeks after ovariectomy (ovx), rats were daily injected with subcutaneous human recombinant PTH (1-84)-dosed 30 micrograms/kg (the low dose PTH-treated group) or 300 micrograms/kg (the high dose PTH-treated group), 17 beta-estradiol (the 17 beta-estradiol-treated group, 30 micrograms/kg) or vehicle (the ovx-alone group), 5 times a week for 4 weeks. The decalcified sections of the distal femoral epiphyseal plate were analyzed on light microscopy after H&E stain, and the lengths of the zones of proliferation, maturing and hypertrophic chondrocytes were measured. The length of the growth plate, the zone of proliferation and the zone of hypertrophic chondrocyte in the ovx-alone group were significantly shorter than those of the sham-operated group. The treatment of 17 beta-estradiol speeded up the differentiation of cells from proliferating chondrocytes to maturing and hypertrophic chondrocytes even though the length of the growth plate was comparable to that of the sham-operated group. Both low and high dose PTH treatments increased the length of the growth plate, and those lengths were comparable to that of the sham-operated group. The fractions of proliferating, maturing and hypertrophic zone in the low dose PTH-treated group were also comparable to those of the sham-operated group. However, high dose PTH treatment slowed down the differentiation of cells from proliferating chondrocytes to maturing and hypertrophic chondrocytes to a greater extent, and therefore the fraction of proliferating chondrocytes of the high dose PTH-treated group was larger than that of the low dose PTH-treated group (73.8 +/- 1.8 Vs 63.3 +/- 1.3%, p < 0.005). From these results, we showed that intermittent PTH treatment could promote linear growth in the ovariectomized growing rat. We propose that PTH may be an alternative drug candidate for promoting linear growth of long bones without the risk for early closure of the growth plate. PMID:10333721

  12. Two-site assay of intact parathyroid hormone in primary hyperparathyroidism: studies in basal conditions, following adenoma removal and during calcium and EDTA infusion.

    PubMed

    Mazzuoli, G; Minisola, S; Scarnecchia, L; Pacitti, M T; Carnevale, V; Romagnoli, E; Bigi, F; Bianchi, G

    1990-10-15

    This study has been carried out in order to investigate parathyroid hormone secretion in patients with primary hyperparathyroidism in basal conditions, during stimulation and suppression tests and following successful surgery. Parathyroid gland secretory activity has been evaluated by a highly sensitive immunoradiometric assay (IRMA) which detects only the biologically intact active hormone and with a well established midmolecule (MM) PTH RIA. There was a good correlation between the two assays in basal state (r = 0.779); however the correlation found between serum PTH levels and total calcium values was better for the intact hormone (P less than 0.001) than for the radioimmunoassay (P less than 0.05). Twenty-four hours following surgery, serum intact PTH levels were in all patients less than 10 pg/ml while midmolecule PTH was still detectable, thereafter remaining at a higher level during the next six days. Serum IRMA PTH levels fell rapidly in response to the increase in serum calcium, then there was a trend to reach a plateau; serum midregion PTH levels fell, although slower than those of intact hormone. The percent increase obtained for serum intact hormone levels was higher than that observed for MM RIA, following EDTA stimulation. The results obtained indicate that the assays of intact and midmolecule parathyroid hormone clearly reflect different aspects of hormone metabolism 'in vivo' and may prove therefore to be useful for its investigation in various calcium disorders. PMID:2123754

  13. Daily intermittent decreases in serum levels of parathyroid hormone have an anabolic-like action on the bones of uremic rats with low-turnover bone and osteomalacia

    Microsoft Academic Search

    H Ishii; M Wada; Y Furuya; N Nagano; E. F Nemeth; J Fox

    2000-01-01

    The calcium receptor agonist (calcimimetic) compound NPS R-568 causes rapid decreases in circulating levels of parathyroid hormone (PTH) in rats and humans. We hypothesized that daily intermittent decreases in serum PTH levels may have different effects on bone than do chronically sustained decreases. To test this hypothesis, we compared two NPS R-568 dosing regimens in rats with chronic renal insufficiency

  14. Effects of low-dose parathyroid hormone on bone mass, turnover, and ectopic osteoinduction in a rat model for chronic alcohol abuse

    Microsoft Academic Search

    U. T. Iwaniec; C. H. Trevisiol; G. F. Maddalozzo; C. J. Rosen; R. T. Turner

    2008-01-01

    Parathyroid hormone (PTH) is used clinically in osteoporotic patients to increase bone mass by enhancing bone formation. PTH therapy is not uniformly effective at all skeletal sites and “life-style” factors may modulate the skeletal response to PTH. Alcohol may represent one of these factors. Chronic alcohol abuse is associated with osteoporosis and impaired fracture healing. Therefore, the present study investigated

  15. Influence of Extracellular Matrix Macromolecules on Normal Human Keratinocyte Phenotype and Parathyroid Hormone-Related Protein Secretion and Expression in Vitro

    Microsoft Academic Search

    Eric A. G. Blomme; Michelle T. Weckmann; Charles C. Capen; Thomas J. Rosol

    1998-01-01

    Parathyroid hormone-related protein (PTHrP) is produced by a wide range of neoplastic and normal cells, including keratinocytes where it may be involved in the regulation of cellular growth and differentiation. There is evidence that the nature of the extracellular matrix (ECM) influences gene expression and cell phenotype. The objective of this study was to investigate the phenotype of normal human

  16. Treatment with human parathyroid hormone (1-34) for 18 months increases cancellous bone volume and improves trabecular architecture in ovariectomized cynomolgus monkeys ( Macaca fascicularis)

    Microsoft Academic Search

    C. P Jerome; D. B Burr; T Van Bibber; J. M Hock; R Brommage

    2001-01-01

    A key feature of postmenopausal osteoporosis is the loss of trabecular bone mass and connectivity. The current study focuses on these parameters in the assessment of long-term (12 and 18 months) parathyroid hormone (PTH) therapy and its withdrawal (6 months) in the ovariectomized cynomolgus monkey (Macaca fascicularis), a well-characterized model for bone changes associated with postmenopausal osteoporosis. We used static

  17. Importance of low serum intact parathyroid hormone as a predictor of mortality in hemodialysis and peritoneal dialysis patients: 14 years of prospective observation

    Microsoft Academic Search

    Morrell M. Avram; Neal Mittman; Maung M. Myint; Paul Fein

    2001-01-01

    Excess parathyroid hormone (PTH) has long been considered detrimental to the health of patients with end-stage renal disease. PTH has been implicated as a multisystem uremic toxin, and hyperparathyroidism can be a debilitating complication in dialyzed patients. We have studied prospectively the relationship of enrollment serum intact PTH and various demographic characteristics and other biochemical parameters to all-cause mortality in

  18. 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 adolescents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 der...

  19. Effect of parathyroid hormone related protein, and dihydrotestosterone on proliferation and ornithine decarboxylase mRNA in human prostate cancer cell lines

    Microsoft Academic Search

    Farrokh Asadi; Mohammad Faraj; Sadegh Malakouti; Subhash C. Kukreja

    2001-01-01

    Objectives: Parathyroid hormone related protein (PTHrP) has beenidentified as the major hormone responsible for the syndrome of humoralhypercalcemia of malignancy (HHM). Recent studies have shown that a largenumber of prostate tumors demonstrate the presence of PTHrP despite thefact that prostate cancer is rarely associated with the HHM syndrome. Otherstudies have indicated that PTHrP behaves as an early response gene,which stimulates

  20. Defective renal maintenance of the vitamin D endocrine system impairs vitamin D renoprotection: a downward spiral in kidney disease

    Microsoft Academic Search

    Adriana S Dusso; Masanori Tokumoto

    2011-01-01

    In kidney disease, the progressive loss of renal capacity to produce calcitriol, the vitamin D hormone, is a key contributor to elevations in parathyroid hormone (PTH) and mineral and skeletal disorders predisposing to renal and cardiovascular damage, ectopic calcifications, and high mortality rates. Thus, the safe correction of calcitriol deficiency to suppress PTH has been the treatment of choice for

  1. Parathyroid hormone plus alendronate in osteoporosis: a meta-analysis of randomized controlled trials

    PubMed Central

    Zhang, Qinggang; Qian, Jing; Zhu, Yuchang

    2015-01-01

    Background: Parathyroid hormone (PTH) increases both bone formation (BMD) and bone resorption, whereas alendronate reduces bone resorption. It is possible that the combination therapy of PTH with alendronate will enhance their effects on BMD. Therefore, we conducted this meta-analysis to evaluate the efficacy of the combination therapy of PTH with alendronate in the treatment of patients with osteoporosis. Methods: A comprehensive literature search of PubMed, Embase, and Web of Science was conducted to identify relative studies. Eligible studies were randomized controlled trials (RCT), which assessed the efficacy of combination therapy in patients with osteoporosis. The outcomes included the mean percent increases in BMD of lumbar spine, femoral neck, total hip, and distal radius. Weighted mean difference (WMD) with 95% confidence intervals (CIs) were calculated using of random-effects or fixed-effects model, depending on the heterogeneity between the included studies. Results: Six RCTs with a total number of 833 patients were included in this meta-analysis. The pooled estimates showed that, the combination therapy of PTH with alendronate resulted in a higher mean percent change of increased BMD in distal radius (WMD = 2.45, 95% CI: 1.58, 3.31; P = 0.000), but not in lumbar spine (WMD = -0.83, 95% CI: -3.48, 1.81; P = 0.538), femoral neck (WMD = -0.99, 95% CI: -2.04, 0.07; P = 0.068), and total hip (WMD = -0.06, 95% CI: -0.93, 0.81; P = 0.892). The subgroup analysis based on the dosage and schedule of PTH, study duration, gender of patients, and anabolic agents, were conducted. And results revealed that among the patients in the combination therapy group, greater increases in the spine BMD were observed when the PTH was administered with a dosage of 20 ?g (WMD = 2.33, 95% CI: 1.24, 3.43; P = 0.000), or the treatment duration lasted more than 12 months (WMD = 2.23, 95% CI: 1.00, 3.47; P = 0.000), or the combination therapy was used in osteoporosis women (WMD = 1.58, 95% CI: 0.63, 2.53; P = 0.001). However, the combination of PTH of 40 ?g with alendronate produced a decrease in the BMD at spine (WMD = -4.56, 95% CI: -7.56, -1.56; P = 0.003) and femoral neck (WMD = -5.82, 95% CI: -9.91, -1.72; P = 0.005). Conclusion: Our findings indicated that the addition of alendronate to PTH in the treatment of osteoporosis, reduced the ability of PTH therapy to increase the BMD at the lumbar spine, femoral neck, and total hip.

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

    PubMed

    Kakuta, Takatoshi; Sawada, Kaichiro

    2014-12-01

    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

  3. Inhibition of parathyroid hormone release by maitotoxin, a calcium channel activator

    SciTech Connect

    Fitzpatrick, L.A.; Yasumoto, T.; Aurbach, G.D.

    1989-01-01

    Maitotoxin, a toxin derived from a marine dinoflagellate, is a potent activator of voltage-sensitive calcium channels. To further test the hypothesis that inhibition of PTH secretion by calcium is mediated via a calcium channel we studied the effect of maitotoxin on dispersed bovine parathyroid cells. Maitotoxin inhibited PTH release in a dose-dependent fashion, and inhibition was maximal at 1 ng/ml. Chelation of extracellular calcium by EGTA blocked the inhibition of PTH by maitotoxin. Maitotoxin enhanced the effects of the dihydropyridine calcium channel agonist (+)202-791 and increased the rate of radiocalcium uptake in parathyroid cells. Pertussis toxin, which ADP-ribosylates and inactivates a guanine nucleotide regulatory protein that interacts with calcium channels in the parathyroid cell, did not affect the inhibition of PTH secretion by maitotoxin. Maitotoxin, by its action on calcium channels allows entry of extracellular calcium and inhibits PTH release. Our results suggest that calcium channels are involved in the release of PTH. Inhibition of PTH release by maitotoxin is not sensitive to pertussis toxin, suggesting that maitotoxin may act distal to the site interacting with a guanine nucleotide regulatory protein, or maitotoxin could interact with other ions or second messengers to inhibit PTH release.

  4. Intestinal absorption of calcium and phosphorus: Experiments on interaction between vitamin D and adrenocortical hormone

    Microsoft Academic Search

    M. Teotia; S. P. S. Teotia; T. Raman; N. L. Sharma; R. K. Singh

    1975-01-01

    Summary  In order to study the effects of vitamin D (calciferol) and its inter-relationship to adrenocortical hormone (prednisolone)\\u000a metabolic balance studies were performed in 10 normal children and 10 children with vitamin D deficiency rickets.\\u000a \\u000a An increase in the intestinal absorption of calcium and phosphorus due to administration of vitamin D was observed in all\\u000a the children with rickets. The initial

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

    PubMed Central

    2014-01-01

    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

  6. Vitamin D requirements: current and future1,2

    Microsoft Academic Search

    Connie M Weaver; James C Fleet

    2004-01-01

    TherequirementsforvitaminDwerelastsetin1997bytheFoodand Nutrition Board of the Institute of Medicine. Intakes were assumed to come from diet, and values were based on achievement of ade- quate vitamin D status and on observed values to prevent seasonal variations in parathyroid hormone concentrations. Serum 25- hydroxyvitaminDconcentrationswereconsideredthebestindicator of vitamin D adequacy, because the production of 25-hydroxy- vitamin D is not regulated. Normal ranges were obtained

  7. Prevalence and Impact of Vitamin D Insufficiency in Southern Chinese Adults

    Microsoft Academic Search

    W. Z. M. Wat; J. Y. Y. Leung; S. Tam; A. W. C. Kung

    2007-01-01

    Introduction: Vitamin D is a vital element for bone health but the problem of vitamin D deficiency is underestimated in Hong Kong. Methods: Serum 25(OH)D and parathyroid hormone (PTH) levels were evaluated in 382 community dwelling Chinese adults >50 years for their relation with bone mineral density (BMD) and risks of osteoporotic fractures and falls. Results: The mean age of

  8. 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

    Pike, J. Wesley

    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

  9. Vitamin D, secondary hyperparathyroidism, and preeclampsia123

    PubMed Central

    Scholl, Theresa O; Chen, Xinhua; Stein, T Peter

    2013-01-01

    Background: Secondary hyperparathyroidism, which is defined by a high concentration of intact parathyroid hormone when circulating 25-hydroxyvitamin D [25(OH)D] is low, is a functional indicator of vitamin D insufficiency and a sign of impaired calcium metabolism. Two large randomized controlled trials examined effects of calcium supplementation on preeclampsia but did not consider the vitamin D status of mothers. Objective: We examined the association of secondary hyperparathyroidism with risk of preeclampsia. Design: Circulating maternal 25-hydroxyvitamin D [25(OH)D] and intact parathyroid hormone were measured at entry to care (mean ± SD: 13.7 ± 5.7 wk) using prospective data from a cohort of 1141 low-income and minority gravidae. Results: Secondary hyperparathyroidism occurred in 6.3% of the cohort and 18.4% of women whose 25(OH)D concentrations were <20 ng/mL. Risk of preeclampsia was increased 2.86-fold (95% CI: 1.28-, 6.41-fold) early in gestation in these women. Gravidae with 25(OH)D concentrations <20 ng/mL who did not also have high parathyroid hormone and women with high parathyroid hormone whose 25(OH)D concentrations were >20 ng/mL were not at increased risk. Intact parathyroid hormone was related to higher systolic and diastolic blood pressures and arterial pressure at week 20 before clinical recognition of preeclampsia. Energy-adjusted intakes of total calcium and lactose and circulating 25(OH)D were correlated inversely with systolic blood pressure or arterial pressure and with parathyroid hormone. Conclusion: Some women who are vitamin D insufficient develop secondary hyperparathyroidism, which is associated with increased risk of preeclampsia. PMID:23885046

  10. Calciotropic hormones in elderly people with and without hip fracture

    Microsoft Academic Search

    C. L. Benhamou; D. Tourliere; J. B. Gauvain; G. Picaper; M. Audran; P. Jallet

    1995-01-01

    The effects of age on calciotropic hormones are not completely understood. The presence of secondary hyperparathyroidism has previously been demonstrated, particularly in patients with hip fracture. The role of a disturbance of vitamin D metabolism, especially a defect in la-hydroxylation, is debated. The aim of this study was to compare serum parathyroid hormone (PTH), osteocalcin and vitamin D metabolites (25(OH)D

  11. Paradoxical actions of exogenous and endogenous parathyroid hormone-related protein on renal vascular smooth muscle cell proliferation: reversion in the SHR model of genetic hypertension

    Microsoft Academic Search

    THIERRY MASSFELDER; NATHALIE TAESCH; NICOLE ENDLICH; ANNE EICHINGER; BENOIT ESCANDE; KARLHANS ENDLICH; MARIETTE BARTHELMEBS; JEAN-JACQUES HELWIG

    2001-01-01

    In previous studies, added parathyroid hormone-related protein (PTHrP) inhibits whereas transfected PTHrP stimulates the proliferation of A10 aortic smooth muscle cells by nuclear translocation of the peptide. In the present studies, we asked whether these paradoxical trophic actions of PTHrP occur in smooth muscle cells (SMC) cultured from small intra- renal arteries of, and whether they are altered in, 12-wk-old

  12. Cancellous and cortical bone architecture and turnover at the iliac crest of postmenopausal osteoporotic women treated with parathyroid hormone 1–84

    Microsoft Academic Search

    R. R. Recker; S. P. Bare; S. Y. Smith; A. Varela; M. A. Miller; S. A. Morris; J. Fox

    2009-01-01

    Treatment with parathyroid hormone [PTH(1–84)] increases lumbar spine bone mineral density and decreases vertebral fractures, but its effects on bone microarchitecture are unknown. We obtained iliac crest biopsies from postmenopausal osteoporotic women given placebo (n=8) or 100 ?g PTH(1–84) for 18 (n=8) or 24 (n=7) months to assess cancellous and cortical bone formation and structure. At 18 months, cancellous bone volume (BV\\/TV)

  13. Dietary boron supplementation enhanced the action of estrogen, but not that of parathyroid hormone, to improve trabecular bone quality in ovariectomized rats

    Microsoft Academic Search

    Matilda H.-C. Sheng; L. Janette Taper; Hugo Veit; Hao Qian; Sanford J. Ritchey; K.-H. William Lau

    2001-01-01

    This study investigated whether boron would enhance the ability of 17?-estradiol (E2) or parathyroid hormone (PTH) to improve bone quality in ovariectomized OVX rats. Adult OVX rats were treated for 5 wk with\\u000a vehicle, boron (5 ppm as boric acid), E2 (30 µg\\/kg\\/d, sc), PTH (60 µg\\/kg\\/d, sc), or a combination of boron and E2 or PTH, respectively. The E2

  14. Characterization of the human and mouse genes encoding the tuberoinfundibular peptide of 39 residues, a ligand of the parathyroid hormone receptor family

    Microsoft Academic Search

    I A Hansen; O Jakob; S Wortmann; T Arzberger; B Allolio; E Blind

    2002-01-01

    The polypeptide TIP39 (tuberoinfundibular peptide of 39 residues) is a potent activator of the parathyroid hormone (PTH)-2 receptor (P2R) and an antagonist of the PTH-1 receptor (P1R). To clarify its possible physiological func- tion(s), we studied its interaction with the human P1R and P2R and examined the expression of TIP39 in man and mouse. To find out possible sites of

  15. Regulation of Parathyroid Hormone-Related Protein Secretion and mRNA Expression in Normal Human Keratinocytes and a Squamous Carcinoma Cell Line

    Microsoft Academic Search

    Michelle T. Weckmann; Andrea Gröne; Charles C. Capen; Thomas J. Rosol

    1997-01-01

    Parathyroid hormone-related protein (PTHrP) has been identified as a causative factor in the pathogenesis of humoral hypercalcemia of malignancy (HHM). The regulation and mechanisms of PTHrP secretion in most normal and malignant cells are unknown. PTHrP secretion, mRNA expression, and transcription were measured in neoplastic human squamous carcinoma cells (A253) and normal human foreskin keratinocytes (NHFK) by radioimmunoassay, RNase protection

  16. Effect of transforming growth factor-?1 on parathyroid hormone-related protein secretion and mRNA expression by normal human keratinocytes in vitro

    Microsoft Academic Search

    James R. Werkmeister; Eric A. G. Blomme; Michelle T. Weckmann; Andrea Gröne; Laurie K. McCauley; Andrew B. Wade; John O’Rourke; Charles C. Capen; Thomas J. Rosol

    1998-01-01

    Parathyroid hormone-related protein (PTHrP) is produced by a wide range of neoplastic and normal cells, including keratinocytes\\u000a where it may regulate growth and differentiation. Transforming growth factor-? (TGF-?) is a growth factor produced by many\\u000a cells, including keratinocytes where it regulates epidermal homeostasis. TGF-? has been reported to be cosecreted with PTHrP\\u000a in some neoplasms and to stimulate PTHrP production

  17. Ovarian carcinoma producing parathyroid hormone-related protein causing hypercalcemia and metastatic calcification detected on 18F-FDG PET-CT

    PubMed Central

    Agarwal, Krishan Kant; Karunanithi, Sellam; Jain, Sachin; Kumar, Rakesh

    2013-01-01

    Hypercalcemia is associated with gynecologic malignant diseases, and cases involving various organs such as the uterus, ovaries, vulva, and vagina. This may be due to elevated levels of parathyroid hormone-related peptide (PTHrP). We describe here two cases of ovarian carcinoma simultaneously producing PTHrP that caused hypercalcemia and metastatic calcification detected on 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT). PMID:24379537

  18. Chondrogenic differentiation of clonal mouse embryonic cell line ATDC5 in vitro: differentiation-dependent gene expression of parathyroid hormone (PTH)\\/PTH-related peptide receptor

    Microsoft Academic Search

    Chisa Shukunami; Chohei Shigeno; Tadao Atsumi; Kiyoto Ishizeki; Fujio Suzuki; Yuji Hiraki

    1996-01-01

    The regulatory role of parathyroid hormone (PTH)\\/PTH-related peptide (PTHrP) signaling has been implicated in embryonic skeletal development. Here, we studied chondrogenic differentiation of the mouse embryonal carcinoma-derived clonal cell line ATDC5 as a model of chondrogenesis in the early stages of endochondral bone development. ATDC5 cells retain the properties of chondroprogenitor cells, and rapidly proliferate in the presence of 5%

  19. Report of a Patient with a High Level of Parathyroid Hormone-Related Peptide Associated with Malignant Lymphoma Involving Multiple Bony Lesions

    Microsoft Academic Search

    Naoko Kinugawa; Yuri Okimoto; Naoko Teraoka; Eiko Sakao; Hiroshi Horie

    2002-01-01

    Hypercalcemia in malignant lymphoma is not common. Our case of malignant lymphoma with multiple bony lesions showed hypercalcemia (13 mg\\/dl) at the time of bone marrow relapse. The serum level of parathyroid hormone-related peptide increased to 142 pmol\\/l, which may be secreted by malignant lymphoma cells. The course of the patient was aggressive and she died from bone marrow relapse

  20. Impact of supplementary high calcium milk with additional magnesium on parathyroid hormone and biochemical markers of bone turnover in postmenopausal women

    Microsoft Academic Search

    J Hilary Green; Chris Booth; Richard Bunning

    2002-01-01

    The aim of this study was to investigate the impact of magnesium-enriched, high-calcium milk on serum parathyroid hormone (PTH) and biochemical markers of bone turnover in postmenopausal women. We recruited 50 healthy postmenopausal women to take part in this randomised controlled study. Half of the women consumed two serves of high-calcium skim milk enriched with magnesium (milk group) and half

  1. The anabolic effects of parathyroid hormone on cortical bone mass, dimensions and strength—assessed in a sexually mature, ovariectomized rat model

    Microsoft Academic Search

    Li. Mosekilde; C. C. Danielsen; C. H. Sřgaard; J. E. McOsker; T. J. Wronski

    1995-01-01

    The aim of the study was to determine the effect of parathyroid hormone (PTH), the antiresorptive agents estrogen and bisphosphonate (risedronate), and also the combination of PTH with these antiresorptive drugs on femoral cortical bone mass, dimensions and strength in a sexually mature, ovariectomized rat model. A total of 138, 3-month-old SpragueDawley rats were randomized into seven groups: 1—sham operated

  2. [The effect of thyroparathyroidectomy, parathyroid hormone and calcitonin on plasma strontium in rats].

    PubMed

    Córdova, A; Soteras, F; Del Villar, V; Elósegui, L M; Escanero, J F

    1990-06-01

    The effect of thyroparathyroidectomy (TPTX) on the plasmatic Sr concentrations in rats previously supplemented with this element, has been studied, as well as its effect on the treatment of TPTX rats with hormonal combinations and, finally, the one presenting hormonal excess or defect of the phosphocalcium metabolism regulating hormones: parathormone (PTH) and calcitonin (CT). Twenty four hours after TPTX, the plasmatic Sr concentrations show a pattern similar to those of Ca and Mg and contrary to Pi. The subsequent evolution is different, as the plasmatic concentrations increase, probably due to the maintenance of Sr supplementation. The administration of this element to TPTX rats and the treatment with a hormonal combination with two of the following hormones: PTH, CT and T4 antagonize the hormonal effect on the restoration of the plasmatic concentrations of the elements analyzed. The PTH excess and defect (TPTX treated with CT + T4) show plasmatic increases in Sr; the CT excess provokes decreases while the defect (administration of PTH + T4) causes increases. The T4 administration reproduces the CT effects, but inconsistently. These results suggest that CT may be the hormone that plays a regulating role in the plasmatic Sr concentrations. PMID:2274697

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

    PubMed Central

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

    1992-01-01

    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

  4. Conformational Changes in the Parathyroid Hormone Receptor Associated with Activation by Agonist

    Microsoft Academic Search

    Beena E. Thomas; Iwona Woznica; Dale F. Mierke; Angela Wittelsberger; Michael Rosenblatt

    2008-01-01

    Binding of hormones to their cognate G protein- coupled receptors (GPCRs) induces conforma- tional shifts within the receptor based on evidence from a few hormone-receptor systems. Employing an engineered disulfide bond formation strategy and guided by a previously established model of the PTH-PTH receptor (PTHR)1 bimolecular com- plex, we set out to document and characterize the nature of agonist-induced changes

  5. Immunohistochemical analysis of low?grade and high?grade prostate carcinoma: relative changes of parathyroid hormone?related protein and its parathyroid hormone 1 receptor, osteoprotegerin and receptor activator of nuclear factor?kB ligand

    PubMed Central

    Pérez?Martínez, Francisco C; Alonso, Verónica; Sarasa, José L; Nam?Cha, Syon?Ghyun; Vela?Navarrete, Remigio; Manzarbeitia, Félix; Calahorra, Francisco J; Esbrit, Pedro

    2007-01-01

    Aim To investigate multiple bone cytokines produced by prostate carcinoma (PCa) as a novel strategy to differentiate potential aggressiveness in localised PCa using immunohistochemical analysis. Methods A total of 47 cases of PCa undergoing radical prostatectomy or transurethral prostatic resection at our institution (Fundación Jiménez Díaz (Grupo Capio), Madrid, Spain) between January 1991 and June 1998 were identified as low?grade (?4; n?=?22) or high?grade (?7, excluding 7 (3+4) cases; n?=?25) PCa according to Gleason grade. PCa specimens were immunostained for: parathyroid hormone (PTH)?related protein (PTHrP), the PTH1 receptor, osteoprotegerin and receptor activator of nuclear factor?? B ligand (RANKL), as well as Ki67 (a proliferation marker) and CD34 (an angiogenesis marker). Results PCa samples showed an increased immunostaining for both osteoprotegerin and RANKL, associated with tumour grade and PTHrP positivity, in the tumoral epithelium. Using a score value of 4—corresponding to moderate staining—as cut?off, the best sensitivity value was for PTHrP (with C?terminal antiserum C6; 100 %); wheras the best specificity value was for RANKL (95 %). Conclusions All the evaluated factors are overexpressed mainly in the high?grade tumours. Our findings indicate that, in most patients with PCa (with Ki67 values between 1% and 9%), sequential determination of C?terminal PTHrP and RANKL immunoreactivities is a useful approach to discriminate low?grade and high?grade tumours. PMID:16775117

  6. Gata3 cooperates with Gcm2 and MafB to activate parathyroid hormone gene expression by interacting with SP1.

    PubMed

    Han, Song-Iee; Tsunekage, Yukino; Kataoka, Kohsuke

    2015-08-15

    Haploinsufficiency of the Gata3 gene, which encodes a zinc-finger transcription factor, is associated with the disorder hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome in humans. However, the roles of Gata3 in transcriptional regulation in the parathyroid glands are not well-understood. In this study, we show that Gata3 activates transcription of parathyroid hormone (PTH), which is secreted from parathyroid glands and is critical for regulating serum calcium and phosphate homeostasis. Gata3 interacted with Gcm2 and MafB, two known transcriptional regulators of parathyroid development, and synergistically stimulated the PTH promoter. An SP1-binding element (GC box) located within the PTH-promoter proximal region was critical for activating transcription by Gata3. In addition, the ubiquitous transcription factor SP1 also interacted with Gata3 as well as MafB and Gcm2, and HDR syndrome-associated Gata3 mutants were defective in activating the PTH promoter. These results suggest that Gata3 is a critical regulator of PTH gene expression. PMID:25917456

  7. Acute-onset hypomagnesemia-induced hypocalcemia caused by the refractoriness of bones and renal tubules to parathyroid hormone.

    PubMed

    Yamamoto, Masahiro; Yamaguchi, Toru; Yamauchi, Mika; Yano, Shozo; Sugimoto, Toshitsugu

    2011-11-01

    Chronic hypomagnesemia is closely associated with hypocalcemia, which is caused by impaired parathyroid hormone (PTH) secretion or the refractoriness of bone and renal tubules to PTH. The dominant mechanism of acute-onset, hypomagnesemia-induced hypocalcemia is currently unclear. An 83-year-old man who had undergone chemotherapy with carboplatin for prostate cancer suffered from acute diarrhea and finger paresthesia. Laboratory data confirmed hypocalcemia as well as hypomagnesemia. Urinary calcium levels were not measured. However, the urinary fractional excretion of Mg (FE(Mg)) was elevated. Despite elevated PTH levels, the renal tubular maximal reabsorption rate of phosphate to GFR (TmP/GFR) was elevated, and bone formation and resorption markers were suppressed. A magnesium loading test revealed a clear magnesium deficiency. After administration of magnesium, bone marker levels were increased, and TmP/GFR was reduced to normal levels, despite the persistent elevation of PTH. Serum calcium levels eventually increased to approximately the reference range. Clinical histories and these observations both suggest that when patients with hypomagnesemia-induced hypocalcemia rapidly lose magnesium through complications such as diarrhea, the primary cause may be the refractoriness of bone and renal tubules to PTH, rather than impaired PTH secretion. PMID:21594582

  8. Obtusifolin suppresses phthalate esters-induced breast cancer bone metastasis by targeting parathyroid hormone-related protein.

    PubMed

    Hsu, Ya-Ling; Tsai, Eing-Mei; Hou, Ming-Feng; Wang, Tsu-Nai; Hung, Jen-Yu; Kuo, Po-Lin

    2014-12-10

    This study is the first to demonstrate that parathyroid hormone-related protein (PTHrP), produced by human breast cancer cells after exposure to phthalate esters, contributes to bone metastasis by increasing osteoclastogenesis. This is also the first to reveal that obtusifolin reverses phthalate esters-mediated bone resorption. Human breast cancer cells were treated with dibutyl phthalate (DBP), harvested in conditioned medium, and cultured to osteoblasts or osteoclasts. Cultures of osteoblasts with DBP-MDA-MB-231-CM increased the osteoclastogenesis activator RANKL (receptor activator of nuclear factor ?-B ligand) and M-CSF (macrophage colony-stimulating factor). PTHrP was secreted in MDA-MB-231 cells. DBP-MDA-MB-231-CM reduced osteoblasts to produce osteoprotegerin, an osteoclastogenesis inhibitor, while DBP mediated PTHrP up-regulation, increasing IL-8 secretion in MDA-MB-231 and contributing to breast cancer-mediated osteoclast differentiation and bone resorption. Obtusifolin, a major bioactive compound present in Cassia tora L., suppressed phthalate esters-mediated bone resorption. Therefore, obtusifolin may be a novel anti-breast-cancer bone metastasis agent. PMID:25415928

  9. Parathyroid hormone-related protein has an anorexigenic activity via activation of hypothalamic urocortins 2 and 3.

    PubMed

    Asakawa, Akihiro; Fujimiya, Mineko; Niijima, Akira; Fujino, Kazunori; Kodama, Noriko; Sato, Yuki; Kato, Ikuo; Nanba, Hiroaki; Laviano, Alessandro; Meguid, Michael M; Inui, Akio

    2010-09-01

    Cancer cachexia is reported to be a major cause of cancer-related death. Since the pathogenesis is not entirely understood, only few effective therapies have been established. Since myriad tumors produce parathyroid hormone-related protein (PTHrP), plasma concentrations of PTHrP are increased in cancer cachexia. We measured the food intake, gastric emptying, conditioned taste aversion (CTA), and gene expression of hypothalamic neuropeptides in mice after administering PTHrP intraperitoneally. We administered PTHrP intravenously in rats and examined the gastroduodenal motility and vagal nerve activities. We also examined whether chronic administration of PTHrP influenced the food intake and body weight. Peripherally administered PTHrP induced negative energy balance by decreasing the food intake and gastric emptying; however, it did not induce CTA. The mechanism involved the activation of hypothalamic urocortins 2 and 3 through vagal afferent pathways and the suppression of gastroduodenal motor activity. The continuous infusion of PTHrP reduced the food intake and body weight gain with a concomitant decrease in the fat and skeletal muscle. Our findings suggest that PTHrP influences the food intake and body weight; therefore, PTHrP can be considered as a therapeutic target for cancer cachexia. PMID:20188481

  10. Role of acetylated human AP-endonuclease (APE1/Ref-1) in regulation of the parathyroid hormone gene

    PubMed Central

    Bhakat, Kishor K.; Izumi, Tadahide; Yang, Suk-Hoon; Hazra, Tapas K.; Mitra, Sankar

    2003-01-01

    The human AP-endonuclease (APE1/Ref-1), a multifunctional protein central to repairing abasic sites and single-strand breaks in DNA, also plays a role in transcriptional regulation. Besides activating some transcription factors, APE1 is directly involved in Ca2+-dependent downregulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs) present in the PTH promoter. Here we show that APE1 is acetylated both in vivo and in vitro by the transcriptional co-activator p300 which is activated by Ca2+. Acetylation at Lys6 or Lys7 enhances binding of APE1 to nCaRE. APE1 stably interacts with class I histone deacetylases (HDACs) in vivo. An increase in extracellular calcium enhances the level of acetylated APE1 which acts as a repressor for the PTH promoter. Moreover, chromatin immunoprecipitation (ChIP) assay revealed that acetylation of APE1 enhanced binding of the APE1–HDACs complex to the PTH promoter. These results indicate that acetylation of APE1 plays an important role in this key repair protein’s action in transcriptional regulation. PMID:14633989

  11. The Proteasome Inhibitor Carfilzomib Suppresses Parathyroid Hormone-induced Osteoclastogenesis through a RANKL-mediated Signaling Pathway.

    PubMed

    Yang, Yanmei; Blair, Harry C; Shapiro, Irving M; Wang, Bin

    2015-07-01

    Parathyroid hormone (PTH) induces osteoclast formation and activity by increasing the ratio of RANKL/OPG in osteoblasts. The proteasome inhibitor carfilzomib (CFZ) has been used as an effective therapy for multiple myeloma via the inhibition of pathologic bone destruction. However, the effect of combination of PTH and CFZ on osteoclastogenesis is unknown. We now report that CFZ inhibits PTH-induced RANKL expression and secretion without affecting PTH inhibition of OPG expression, and it does so by blocking HDAC4 proteasomal degradation in osteoblasts. Furthermore, we used different types of culture systems, including co-culture, indirect co-culture, and transactivation, to assess the effect of CFZ on PTH action to induce osteoclastogenesis. Our results demonstrated that CFZ blocks PTH-induced osteoclast formation and bone resorption by its additional effect to inhibit RANKL-mediated I?B degradation and NF-?B activation in osteoclasts. This study showed for the first time that CFZ targets both osteoblasts and osteoclasts to suppress PTH-induced osteoclast differentiation and bone resorption. These findings warrant further investigation of this novel combination in animal models of osteoporosis and in patients. PMID:25979341

  12. Regulation of beta catenin signaling and parathyroid hormone anabolic effects in bone by the matricellular protein periostin

    PubMed Central

    Bonnet, Nicolas; Conway, Simon J.; Ferrari, Serge L.

    2012-01-01

    Periostin (Postn) is a matricellular protein preferentially expressed by osteocytes and periosteal osteoblasts in response to mechanical stimulation and parathyroid hormone (PTH). Whether and how periostin expression influences bone anabolism, however, remains unknown. We investigated the skeletal response of adult Postn?/? and Postn+/+ mice to intermittent PTH. Compared with Postn+/+, Postn?/? mice had a lower bone mass, cortical bone volume, and strength response to PTH. PTH-stimulated bone-forming indices were all significantly lower in Postn?/? mice, particularly at the periosteum. Furthermore, in vivo stimulation of Wnt-?-catenin signaling by PTH, as evaluated in TOPGAL reporter mice, was inhibited in the absence of periostin (TOPGAL;Postn?/? mice). PTH stimulated periostin and inhibited MEF2C and sclerostin (Sost) expression in bone and osteoblasts in vitro. Recombinant periostin also suppressed Sost expression, which was mediated through the integrin ?V?3 receptor, whereas periostin-blocking antibody prevented inhibition of MEF2C and Sost by PTH. In turn, administration of a Sost-blocking antiboby partially restored the PTH-mediated increase in bone mass in Postn?/? mice. In addition, primary osteoblasts from Postn?/? mice showed a lower proliferation, mineralization, and migration, both spontaneously and in response to PTH. Osteoblastic gene expression levels confirmed a defect of Postn?/? osteoblast differentiation with and without PTH, as well as an increased osteoblast apoptosis in the absence of periostin. These data elucidate the complex role of periostin on bone anabolism, through the regulation of Sost, Wnt-?-catenin signaling, and osteoblast differentiation. PMID:22927401

  13. Plasma levels of parathyroid hormone-related peptide are elevated in hyperprolactinemia and correlated to bone density status.

    PubMed

    Stiegler, C; Leb, G; Kleinert, R; Warnkross, H; Ramschak-Schwarzer, S; Lipp, R; Clarici, G; Krejs, G J; Dobnig, H

    1995-05-01

    Osteopenia is an important clinical manifestation of hyperprolactinemia. Bone loss in these patients has mainly been attributed to concomitant deficiency of gonadal hormones rather than to hyperprolactinemia per se. Parathyroid hormone-related peptide (PTHrP) is expressed in human mammary tissue, and elevated circulating PTHrP levels as well as concomitant hypercalcemia have been described during lactation. We sought to determine circulating PTHrP levels in patients with long-standing hyperprolactinemia and whether PTHrP may exert possible systemic effects on bone and mineral metabolism. We studied 45 patients (30 women and 15 men) with persisting hyperprolactinemia 6 +/- 4 years (mean +/- SD) after trans-sphenoidal surgery for prolactin-producing pituitary adenomas. PTHrP levels in 117 healthy controls were 10.6 +/- 7.3 pmol-eq/l (mean +/- SD). In hyperprolactinemic patients, plasma PTHrP was elevated to 30.3 +/- 13.4 pmol-eq/l (p < 0.001, n = 45), and in patients with humoral hypercalcemia of malignancy PTHrP levels were 52.9 +/- 29.6 (p < 0.001 to controls and hyperprolactinemic patients). Fifty-three percent of hyperprolactinemic patients (n = 24) had clearly elevated PTHrP levels (> 2 SD). Retrospective immunocytochemical studies of the removed pituitary adenomas from 19 patients generally showed a higher degree of immunoreactivity for PTHrP (1-34) in all but one case when compared with normal pituitary tissue. Patients with elevated circulating PTHrP levels showed in most instances strong immunoreactivity to PTHrP in 70-100% of tumor cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7639111

  14. Parathyroid hormone levels 1 hour after thyroidectomy: an early predictor of postoperative hypocalcemia

    PubMed Central

    AlQahtani, Awad; Parsyan, Armen; Payne, Richard; Tabah, Roger

    2014-01-01

    Background Parathyroid dysfunction leading to symptomatic hypocalcemia is not uncommon following a total or completion thyroidectomy and is often associated with significant patient morbidity and a prolonged hospital stay. A simple, reliable indicator to identify patients at risk would permit earlier pharmacologic prophylaxis to avoid these adverse outcomes. We examined the role of intact parathormone (PTH) levels 1 hour after surgery as a predictor of post-thyroidectomy hypocalcemia. Methods We prospectively reviewed the cases of consecutive patients undergoing total or completion thyroidectomy. Ionized calcium (Ca2+) and intact PTH levels were measured preoperatively and at 1-, 6- and 24-hour intervals postoperatively. The specificity, sensitivity, negative and positive predictive values of the 1-hour PTH serum levels (PTH-1) in predicting 24-hour post-thyroidectomy hypocalcemia and eucalcemia were determined. Results We reviewed the cases of 149 patients. Biochemical hypocalcaemia (Ca2+ < 1.1 mmol/L) developed in 38 of 149 (25.7%) patients 24 hours after thyroidectomy. The sensitivity, specificity, positive and negative predictive values of a low PTH-1 were 89%, 100%, 97% and 100%, respectively. Conclusion We found that PTH-1 levels were predictive of symptomatic hypocalcemia 24 hours after thyroidectomy. Routine use of this assay should be considered, as it could prompt the early administration of calcitriol in patients at risk of hypocalcemia and allow for the safe and timely discharge of patients expected to remain eucalcemic. PMID:25078927

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

    SciTech Connect

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

    1988-10-01

    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.

  16. Vitamin D — Soltriol The heliogenic steroid hormone: Somatotrophic activator and modulator

    Microsoft Academic Search

    W. E. Stumpf

    1988-01-01

    Evidence from autoradiographic studies with 3H 1,25(OH)2 vitamin D3 (soltriol) about its many sites of nuclear binding and multiple actions suggests that the traditional view of “vitamin D and calcium” is too limited and requires modification. A new concept has been developed which proposes that the skin-derived hormone of sunshine, soltriol, is a somatotrophic activator and modulator that affects all

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

    PubMed Central

    Karaca, Halit

    2014-01-01

    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

  18. Growth Hormone Therapy in Children with Chronic Renal Failure

    PubMed Central

    Cayir, Atilla; Kosan, Celalettin

    2015-01-01

    Growth is impaired in a chronic renal failure. Anemia, acidosis, reduced intake of calories and protein, decreased synthesis of vitamin D and increased parathyroid hormone levels, hyperphosphatemia, renal osteodystrophy and changes in growth hormone-insulin-like growth factor and the gonadotropin-gonadal axis are implicated in this study. Growth is adversely affected by immunosuppressives and corticosteroids after kidney transplantation. Treating metabolic disorders using the recombinant human growth hormone is an effective option for patients with inadequate growth rates. PMID:25745347

  19. Parathyroid hormone and calcitonin interactions in bone: Irradiation-induced inhibition of escape in vitro

    Microsoft Academic Search

    Nancy S. Krieger; Roy S. Feldman; Armen H. Tashjian

    1982-01-01

    Summary  Calcitonin (CT) inhibits hormonally stimulated bone resorption only transiently in vitro. This phenomenon has been termed\\u000a “escape,” but the mechanism for the effect is not understood. One possible explanation is that bone cell differentiation and\\u000a recruitment of specific precursor cells, in response to stimulators of resorption, lead to the appearance of osteoclasts that\\u000a are unresponsive to CT. To test this

  20. Vitamin D Status and Its Relation to Age and Body Mass Index

    Microsoft Academic Search

    Martin G. Bischof; Georg Heinze; Heinrich Vierhapper

    2006-01-01

    Background\\/Aims: While numerous studies have examined 25(OH)-vitamin D3 (25-D) concentrations and their relation to parathyroid hormone (PTH) levels there is only limited information on the interrelation between 25-D, 1,25(OH)2-vitamin D3 (1,25-D) and PTH. It was the aim of this study to assess the vitamin D endocrine system and its relation to age and body mass index (BMI). Methods: This cross-sectional

  1. Conformational changes in the parathyroid hormone receptor associated with activation by agonist.

    PubMed

    Thomas, Beena E; Woznica, Iwona; Mierke, Dale F; Wittelsberger, Angela; Rosenblatt, Michael

    2008-05-01

    Binding of hormones to their cognate G protein-coupled receptors (GPCRs) induces conformational shifts within the receptor based on evidence from a few hormone-receptor systems. Employing an engineered disulfide bond formation strategy and guided by a previously established model of the PTH-PTH receptor (PTHR)1 bimolecular complex, we set out to document and characterize the nature of agonist-induced changes in this family B GPCR. A mutant PTHR1 was generated which incorporates a Factor Xa cleavage site in the third intracellular loop. Treatment with Factor Xa fragments the receptor. However, if a new disulfide bond was formed before exposure to the enzyme, the fragments remain held together. A set of double cysteine-containing mutants were designed to probe the internal relative movements of transmembrane (TM) helices 2 and TM7. PTH enhanced formation of disulfide bonds in the K240C/F447C and A242C/F447C mutants. For the F238C/F447C mutant, a disulfide bond is formed in the basal state, but is disrupted by interaction with PTH. For the D241C/F447C PTHR1 construct, no disulfide bond formation was observed in either the basal or hormone-bound state. These findings demonstrate that the conformation of PTHR1 is altered from the basal state when PTH is bound. Novel information regarding spatial proximities between TM2 and TM7 of PTHR1 and the nature of relative movements between the two transmembrane regions was revealed. The data confirm and extend the experimentally derived model of the PTH-PTHR1 complex and provide insights at a new level of detail into the early events in PTHR1 activation by PTH. PMID:18258686

  2. Conformational Changes in the Parathyroid Hormone Receptor Associated with Activation by Agonist

    PubMed Central

    Thomas, Beena E.; Woznica, Iwona; Mierke, Dale F.; Wittelsberger, Angela; Rosenblatt, Michael

    2008-01-01

    Binding of hormones to their cognate G protein-coupled receptors (GPCRs) induces conformational shifts within the receptor based on evidence from a few hormone-receptor systems. Employing an engineered disulfide bond formation strategy and guided by a previously established model of the PTH-PTH receptor (PTHR)1 bimolecular complex, we set out to document and characterize the nature of agonist-induced changes in this family B GPCR. A mutant PTHR1 was generated which incorporates a Factor Xa cleavage site in the third intracellular loop. Treatment with Factor Xa fragments the receptor. However, if a new disulfide bond was formed before exposure to the enzyme, the fragments remain held together. A set of double cysteine-containing mutants were designed to probe the internal relative movements of transmembrane (TM) helices 2 and TM7. PTH enhanced formation of disulfide bonds in the K240C/F447C and A242C/F447C mutants. For the F238C/F447C mutant, a disulfide bond is formed in the basal state, but is disrupted by interaction with PTH. For the D241C/F447C PTHR1 construct, no disulfide bond formation was observed in either the basal or hormone-bound state. These findings demonstrate that the conformation of PTHR1 is altered from the basal state when PTH is bound. Novel information regarding spatial proximities between TM2 and TM7 of PTHR1 and the nature of relative movements between the two transmembrane regions was revealed. The data confirm and extend the experimentally derived model of the PTH-PTHR1 complex and provide insights at a new level of detail into the early events in PTHR1 activation by PTH. PMID:18258686

  3. Growth characteristics of hormone and vitamin independent photoautotrophic cell suspension cultures from Chenopodium rubrum

    Microsoft Academic Search

    W. Hüsemann

    1981-01-01

    Summary This communication reports the photoautotrophic growth of hormone and vitamin independent cell suspension cultures ofChenopodium rubrum. The transfer of cells from stationary growth into fresh culture medium results in a high protein formation, followed by an exponential phase of cell division, whereas the onset of rapid chlorophyll formation is delayed for 4 days. At the stage of most rapid

  4. Diet supplementation with cholesterol and vitamin E influences rat hormonal and immune status

    Microsoft Academic Search

    B. Si?ska; B. Sotowska; D. Roso?owska-Huszcz; M. Markowska; M. Bo?entowicz; K. Skwar?o-So?ta; J. Gromadzka-Ostrowska

    Diet composition may influence the activity of the HPA and HPT axes, which, in turn, modulates immune system function. The aim of the present study was to investigate the response of rat hormonal and immune parameters to feeding with a standard diet supplemented with cholesterol and vitamin E. The experiment was performed on Wistar rats fed for 6 weeks on

  5. Parathyroid hormone inhibition of Na(+)/H(+) exchanger 3 transcription: Intracellular signaling pathways and transcription factor expression.

    PubMed

    Neri, Elida Adalgisa; Bezerra, Camila Nogueira Alves; Queiroz-Leite, Gabriella Duarte; Polidoro, Juliano Zequini; Rebouças, Nancy Amaral

    2015-06-12

    The main transport mechanism of reabsorption of sodium bicarbonate and fluid in the renal proximal tubules involves Na(+)/H(+) exchanger 3 (NHE3), which is acutely and chronically downregulated by parathyroid hormone (PTH). Although PTH is known to exert an inhibitory effect on NHE3 expression and transcription, the molecular mechanisms involved remain unclear. Here, we demonstrated that, in opossum kidney proximal tubule (OKP) cells, PTH-induced inhibition of Nhe3 gene promoter occurs even in the core promoter that controls expression of the reporter gene. We found that inhibition of the protein kinase A (PKA) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways transformed PTH from an inhibitor of promoter activity into an activator of that same activity, as did point mutations in the EGR1, Sp1, and Sp3 binding consensus elements in the promoter. In nuclear extracts of PTH-treated OKP cells, we also observed increased expression of EGR1 mRNA and of some Sp3 isoforms. Electrophoretic mobility shift assay showed a supershift of the -61 to -42-bp probe with an anti-EGR1 antibody in PTH-treated cells, suggesting that EGR1 binding is relevant for the inhibitory activity of PTH. We conclude that PTH-induced inhibition of NHE3 transcription is related to higher EGR1 expression; to EGR1 binding to the proximal and core promoters; and to PKA and JAK/STAT pathway activation. This mechanism might be responsible, at least in part, for lower NHE3 expression and sodium reabsorption in renal proximal tubules in the presence of high PTH levels. PMID:25888790

  6. Mobilization of Endogenous Bone Marrow Derived Endothelial Progenitor Cells and Therapeutic Potential of Parathyroid Hormone after Ischemic Stroke in Mice

    PubMed Central

    Wang, Li-Li; Chen, Dongdong; Lee, Jinhwan; Gu, Xiaohuan; Alaaeddine, Ghina; Li, Jimei; Wei, Ling; Yu, Shan Ping

    2014-01-01

    Stroke is a major neurovascular disorder threatening human life and health. Very limited clinical treatments are currently available for stroke patients. Stem cell transplantation has shown promising potential as a regenerative treatment after ischemic stroke. The present investigation explores a new concept of mobilizing endogenous stem cells/progenitor cells from the bone marrow using a parathyroid hormone (PTH) therapy after ischemic stroke in adult mice. PTH 1-34 (80 µg/kg, i.p.) was administered 1 hour after focal ischemia and then daily for 6 consecutive days. After 6 days of PTH treatment, there was a significant increase in bone marrow derived CD-34/Fetal liver kinase-1 (Flk-1) positive endothelial progenitor cells (EPCs) in the peripheral blood. PTH treatment significantly increased the expression of trophic/regenerative factors including VEGF, SDF-1, BDNF and Tie-1 in the brain peri-infarct region. Angiogenesis, assessed by co-labeled Glut-1 and BrdU vessels, was significantly increased in PTH-treated ischemic brain compared to vehicle controls. PTH treatment also promoted neuroblast migration from the subventricular zone (SVZ) and increased the number of newly formed neurons in the peri-infarct cortex. PTH-treated mice showed significantly better sensorimotor functional recovery compared to stroke controls. Our data suggests that PTH therapy improves endogenous repair mechanisms after ischemic stroke with functional benefits. Mobilizing endogenous bone marrow-derived stem cells/progenitor cells using PTH and other mobilizers appears an effective and feasible regenerative treatment after ischemic stroke. PMID:24503654

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

    PubMed

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

    2011-01-01

    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

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

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

    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.

  9. Parathyroid hormone promotes the disassembly of cytoskeletal actin and myosin in cultured osteoblastic cells: Mediation by cyclic AMP

    SciTech Connect

    Egan, J.J.; Gronowicz, G.; Rodan, G.A. (National Institutes of Diabetes, Digestive, and Kidney Diseases, Bethesda, MD (USA))

    1991-01-01

    Parathyroid hormone (PTH) alters the shape of osteoblastic cells both in vivo and in vitro. In this study, we examined the effect of PTH on cytoskeletal actin and myosin, estimated by polyacrylamide gel electrophoresis of Triton X-100 (1%) nonextractable proteins. After 2-5 minutes, PTH caused a rapid and transient decrease of 50-60% in polymerized actin and myosin associated with the Triton X-100 nonextractable cytoskeleton. Polymerized actin returned to control levels by 30 min. The PTH effect was dose-dependent with an IC50 of about 1 nM, and was partially inhibited by the (3-34) PTH antagonist. PTH caused a rapid transient rise in cyclic AMP (cAMP) in these cells that peaked at 4 min, while the nadir in cytoskeletal actin and myosin was recorded around 5 min. The intracellular calcium chelator Quin-2/AM (10 microM) also decreased cytoskeletal actin and myosin, to the same extent as did PTH (100 nM). To distinguish between cAMP elevation and Ca++ reduction as mediators of PTH action, we measured the phosphorylation of the 20 kD (PI 4.9) myosin light chain in cells preincubated with (32P)-orthophosphate. The phosphorylation of this protein decreased within 2-3 min after PTH addition and returned to control levels after 5 min. The calcium ionophore A-23187 did not antagonize this PTH effect. Visualization of microfilaments with rhodamine-conjugated phalloidin showed that PTH altered the cytoskeleton by decreasing the number of stress fibers. These changes in the cytoskeleton paralleled changes in the shape of the cells from a spread configuration to a stellate form with retracting processes. The above findings indicate that the alteration in osteoblast shape produced by PTH involve relatively rapid and transient changes in cytoskeletal organization that appear to be mediated by cAMP.

  10. Covalent labeling of a high-affinity, guanyl nucleotide sensitive parathyroid hormone receptor in canine renal cortex

    SciTech Connect

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

    1987-04-07

    Putative parathyroid hormone (PTH) receptors in canine renal membranes were affinity labeled with /sup 125/I-bPTH(1-34) using the heterobifunctional cross-linking reagent N-hydroxysuccinimidyl 4-azido-benzoate. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the presence of a major 85,000 molecular weight (M/sub r/) PTH binding component, the labeling of which was inhibited by nanomolar concentrations of unlabeled PTH and by micromolar concentrations of 5'-guanylyl imidodiphosphate (Gpp-(NH)p). Labeling was not influenced by the unrelated peptides insulin and arginine vasopressin. Minor PTH binding components of M/sub r/ 55,000 and 130,000 were also seen, and labeling of these was likewise sensitive to unlabeled PTH and to Gpp(NH)p. Omission of protease inhibitors during the isolation of plasma membranes resulted in the loss of the M/sub r/ 85,000 PTH binding species and the appearance of an M/sub r/ 70,000 form. Several minor PTH binding components also were observed. Equilibrium binding studies showed that such membranes had an affinity for PTH indistinguishable from that in membranes isolated with protease inhibitors and displaying a major M/sub r/ 85,000 PTH binding species. The authors conclude that the major form of the adenylate cyclase coupled PTH receptor in canine renal membranes is an M/sub r/ 85,000 protein. An endogenous enzyme, probably a lysosomal cathepsin, can cleave this form to produce an M/sub r/ 70,000 receptor that retains full functional activity with respect to high-affinity, guanyl nucleotide sensitive PTH binding. The ability to covalently label the PTH receptor in high yield represents a major step toward the structural characterization of this important detector molecule.

  11. An Essential Role for Parathyroid Hormone in Gill Formation and Differentiation of Ion-Transporting Cells in Developing Zebrafish.

    PubMed

    Kwong, Raymond W M; Perry, Steve F

    2015-07-01

    In vertebrates, parathyroid hormone (PTH) is important for skeletogenesis and Ca(2+) homeostasis. However, little is known about the molecular mechanisms by which PTH regulates skeleton formation and Ca(2+) balance during early development. Using larval zebrafish as an in vivo model system, we determined that PTH1 regulates the differentiation of epithelial cells and the development of craniofacial cartilage. We demonstrated that translational gene knockdown of PTH1 decreased Ca(2+) uptake at 4 days after fertilization. We also observed that PTH1-deficient fish exhibited reduced numbers of epithelial Ca(2+) channel (ecac)-expressing cells, Na(+)/K(+)-ATPase-rich cells, and H(+)-ATPase-rich cells. Additionally, the density of epidermal stem cells was decreased substantially in the fish experiencing PTH1 knockdown. Knockdown of PTH1 caused a shortening of the jaw and impeded the development of branchial arches. Results from in situ hybridization suggested that the expression of collagen 2a1a (marker for proliferating chondrocytes) was substantially reduced in the cartilage that forms the jaw and branchial aches. Disorganization of chondrocytes in craniofacial cartilage also was observed in PTH1-deficient fish. The results of real-time PCR demonstrated that PTH1 morphants failed to express the transcription factor glial cell missing 2 (gcm2). Coinjection of PTH1 morpholino with gcm2 capped RNA rescued the phenotypes observed in the PTH1 morphants, suggesting that the defects in PTH1-deficient fish were caused, at least in part, by the suppression of gcm2. Taken together, the results of the present study reveal critical roles for PTH1 in promoting the differentiation of epidermal stem cells into mature ionocytes and cartilage formation during development. PMID:25872007

  12. Synergistic effects of high dietary calcium and exogenous parathyroid hormone in promoting osteoblastic bone formation in mice.

    PubMed

    Feng, Yuxu; Zhou, Min; Zhang, Qunhu; Liu, Huan; Xu, Yong; Shu, Lei; Zhang, Jue; Miao, Dengshun; Ren, Yongxin

    2015-03-28

    In the present study, we investigated whether high dietary Ca and exogenous parathyroid hormone 1-34 fragments (PTH 1-34) have synergistic effects on bone formation in adult mice, and explored the related mechanisms. Adult male mice were fed a normal diet, a high-Ca diet, a PTH-treated diet, or a high-Ca diet combined with subcutaneously injected PTH 1-34 (80 ?g/kg per d) for 4 weeks. Bone mineral density, trabecular bone volume, osteoblast number, alkaline phosphatase (ALP)- and type I collagen-positive areas, and the expression levels of osteoblastic bone formation-related genes and proteins were increased significantly in mice fed the high-Ca diet, the PTH-treated diet, and, even more dramatically, the high-Ca diet combined with PTH. Osteoclast number and surface and the ratio of receptor activator for nuclear factor-?B ligand (RANKL):osteoprotegerin (OPG) were decreased in the high-Ca diet treatment group, increased in the PTH treatment group, but not in the combined treatment group. Furthermore, third-passage osteoblasts were treated with high Ca (5 mM), PTH 1-34 (10?? M) or high Ca combined with PTH 1-34. Osteoblast viability and ALP activity were increased in either the high Ca-treated or PTH-treated cultures and, even more dramatically, in the cultures treated with high Ca plus PTH, with consistent up-regulation of the expression levels of osteoblast proliferation and differentiation-related genes and proteins. These results indicate that dietary Ca and PTH play synergistic roles in promoting osteoblastic bone formation by stimulating osteoblast proliferation and differentiation. PMID:25744000

  13. Distinctive anabolic roles of 1,25-dihydroxyvitamin D(3) and parathyroid hormone in teeth and mandible versus long bones.

    PubMed

    Liu, Hong; Guo, Jian; Wang, Lin; Chen, Ning; Karaplis, Andrew; Goltzman, David; Miao, Dengshun

    2009-11-01

    To assess the roles of 1,25-dihydroxyvitamin D (1,25(OH)(2)D) and parathyroid hormone (PTH) in hard tissue formation in oro-facial tissues, we examined the effect of either 1,25(OH)(2)D or PTH deficiency on dentin and dental alveolar bone formation and mineralization in the mandibles, and osteoblastic bone formation in long bones of 1alpha-hydroxylase knockout (1alpha(OH)ase(-/-)) mice. Compared with wild-type mice, the mineral density was decreased in the teeth and mandibles, and unmineralized dentin (predentin and biglycan immunopositive dentin) and unmineralized bone matrix in the dental alveolar bone were increased in 1alpha(OH)ase(-/-) mice. The dental volume, reparative dentin volume, and dentin sialoprotein immunopositive areas were reduced in 1alpha(OH)ase(-/-) mice. The cortical thickness, dental alveolar bone volume, and osteoblast number were all decreased significantly in the mandibles; in contrast, the osteoblast number and surface were increased in the trabecular bone of the tibiae in 1alpha(OH)ase(-/-) mice consistent with their secondary hyperparathyroidism. The expression of PTH receptor and IGF1 was reduced slightly in mandibles, but enhanced significantly in the long bones in the 1alpha(OH)ase(-/-) mice. To control for the role of secondary hyperparathyroidism, we also examined teeth and mandibles in 6-week-old PTH(-/-) mice. In these animals, dental and bone volumes in mandibles were not altered when compared with their wild-type littermates. These results suggest that 1,25(OH)(2)D(3) plays an anabolic role in both dentin and dental alveolar bone as it does in long bones, whereas PTH acts predominantly in long bones rather than mandibular bone. PMID:19713218

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed Central

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

    2014-01-01

    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

  16. Vitamin D -- the sun hormone. Life in environmental mismatch.

    PubMed

    Göring, H; Koshuchowa, S

    2015-01-01

    While some representatives of the animal kingdom were improving their biological mechanisms and properties for adapting to ever-changing life conditions, the genus Homo was developing backward: human individuals were losing their adaptation to life areas conquered earlier. Losing step-by-step their useful traits including the body hair cover, the primitive genus Homo retained his viability only under very favorable conditions of the equatorial Africa. Protection from UV radiation danger was provided only by pigmentation of skin, hair, and eyes. However, "impoverished" individuals of this genus gained the ability to walk upright. Their hands became free from participation in movement and became fine tools for producing useful instruments, from the stone knife to the computer. The major consequence of upright movement and hand development became the powerful development of the brain. A modern human, Homo sapiens, appeared capable of conquering very diverse new habitats. The human's expansion on the Earth occurred somewhat limited by his dependence on vitamin D. His expansion into new areas with lower Sun activity was partially associated with the loss of skin pigmentation. But there is an open question, whether under these new conditions he is satisfactorily provided with vitamin D. This paper discusses the following problems: how can we ensure a sufficient intake of vitamin D, how much does an individual require for his existence and optimal life, what will be consequences of vitamin D deficiency, and what are the prospects for better provision with vitamin D? PMID:25754035

  17. Hormonal and Anthropometric Predictors of Bone Mass in Healthy Elderly Men: Major Effect of Sex Hormone Binding Globulin, Parathyroid Hormone and Body Weight

    Microsoft Academic Search

    G. Martínez Díaz-Guerra; F. Hawkins; A. Rapado; M. A. Ruiz Díaz; M. Díaz-Curiel

    2001-01-01

    :   Osteoporosis in men is a significant health problem, and factors associated with bone mass are being investigated. Although\\u000a osteoporosis is a typical feature of hypogonadism, the influence of testosterone levels and other hormonal factors on bone\\u000a mass of eugonadal males is unknown. Our aim was to identify several anthropometric and hormonal predictors that could be responsible\\u000a for the variability

  18. Effects of parathyroid hormone-related protein and macrophage inflammatory protein-1? in Jurkat T-cells on tumor formation in vivo and expression of apoptosis regulatory genes in vitro.

    PubMed

    Shu, Sherry T; Dirksen, Wessel P; Lanigan, Lisa G; Martin, Chelsea K; Thudi, Nanda K; Werbeck, Jillian L; Fernandez, Soledad A; Hildreth, Blake E; Rosol, Thomas J

    2012-04-01

    Parathyroid hormone-related protein (PTHrP) and macrophage inflammatory protein-1? (MIP-1?) have been implicated in the pathogenesis of adult T-cell leukemia/lymphoma, but their effects on T-cells have not been well studied. Here we analyzed the functions of PTHrP and MIP-1? on T-cell growth and death both in vitro and in vivo by overexpressing either factor in human Jurkat T-cells. PTHrP or MIP-1? did not affect Jurkat cell growth in vitro, but PTHrP increased their sensitivity to apoptosis. Importantly, PTHrP and MIP-1? decreased both tumor incidence and growth in vivo. To investigate possible mechanisms, polymerase chain reaction (PCR) arrays and real-time reverse transcription (RT)-PCR assays were performed. Both PTHrP and MIP-1? increased the expression of several factors including signal transducer and activator of transcription 4, tumor necrosis factor ?, receptor activator of nuclear factor ?B ligand and death-associated protein kinase 1, and decreased the expression of inhibitor of DNA binding 1, interferon ? and CD40 ligand in Jurkat cells. In addition, MIP-1? also increased the expression of transcription factor AP-2? and PTHrP increased expression of the vitamin D3 receptor. These data demonstrate that PTHrP and MIP-1? exert a profound antitumor effect presumably by increasing the sensitivity to apoptotic signals through modulation of transcription and apoptosis factors in T-cells. PMID:21942940

  19. Effects of parathyroid hormone-related protein and macrophage inflammatory protein-1? in Jurkat T-cells on tumor formation in vivo and expression of apoptosis regulatory genes in vitro

    PubMed Central

    Shu, Sherry T.; Dirksen, Wessel P.; Lanigan, Lisa G.; Martin, Chelsea K.; Thudi, Nanda K.; Werbeck, Jillian L.; Fernandez, Soledad A.; Hildreth, Blake E.; Rosol, Thomas J.

    2012-01-01

    Parathyroid hormone-related protein (PTHrP) and macrophage inflammatory protein-1? (MIP-1?) have been implicated in the pathogenesis of adult T-cell leukemia/lymphoma, but their effects on T-cells have not been well studied. Here we analyzed the functions of PTHrP and MIP-1? on T-cell growth and death both in vitro and in vivo by overexpressing either factor in human Jurkat T-cells. PTHrP or MIP-1? did not affect Jurkat cell growth in vitro, but PTHrP increased their sensitivity to apoptosis. Importantly, PTHrP and MIP-1? decreased both tumor incidence and growth in vivo. To investigate possible mechanisms, polymerase chain reaction (PCR) arrays and real-time reverse transcription (RT)-PCR assays were performed. Both PTHrP and MIP-1? increased the expression of several factors including signal transducer and activator of transcription 4, tumor necrosis factor ?, receptor activator of nuclear factor ?B ligand and death-associated protein kinase 1, and decreased the expression of inhibitor of DNA binding 1, interferon ? and CD40 ligand in Jurkat cells. In addition, MIP-1? also increased the expression of transcription factor AP-2? and PTHrP increased expression of the vitamin D3 receptor. These data demonstrate that PTHrP and MIP-1? exert a profound antitumor effect presumably by increasing the sensitivity to apoptotic signals through modulation of transcription and apoptosis factors in T-cells. PMID:21942940

  20. Effects of electromagnetic stimuli on bone and bone cells in vitro: Inhibition of responses to parathyroid hormone by low-energy low-frequency fields

    PubMed Central

    Luben, Richard A.; Cain, Christopher D.; Chen, Monica Chi-Yun; Rosen, David M.; Adey, W. Ross

    1982-01-01

    Low-energy electromagnetic fields pulsed at frequencies of 10-90 Hz significantly increase healing of chronic fracture nonunions in man. These fields are effective at tissue current levels several orders of magnitude lower than those required for transmembrane depolarization of normal cells. We have examined the effects of two clinically used pulsed electromagnetic fields on cultures of the osteoblast-like mouse bone cell line MMB-1. Both fields significantly reduced cellular production of cAMP in response to parathyroid hormone and osteoclast activating factor. Neither basal nor fluoride-activated levels of adenylate cyclase were altered in membranes from cells cultured in the fields; however, the same membrane preparations exhibited markedly inhibited responses to parathyroid hormone. The fields blocked the inhibitory effects of the hormone on collagen synthesis by MMB-1 cells. However, there was no effect on the inhibition of collagen synthesis by 1,25-dihydroxyvitamin D3, which is believed to act primarily by a nuclear, rather than by a membrane-dependent, mechanism. No significant differences were noted between effects of the two fields, one generating continuous pulse trains (72 Hz) and the other generating recurrent bursts (15 Hz) of shorter pulses. We hypothesize that these field effects are mediated primarily at the plasma membrane of osteoblasts, either by interference with hormone-receptor interactions or by blocking of receptor-cyclase coupling in the membrane. These responses occurred with induced extracellular fields of 1 mV/cm or less, even though transmembrane potential gradients are typically 105 V/cm. PMID:6287472

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

    PubMed Central

    2011-01-01

    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

  2. Parathyroid hormone-related protein and ezrin are up-regulated in human lung cancer bone metastases.

    PubMed

    Deng, Xiyun; Tannehill-Gregg, Sarah H; Nadella, Murali V P; He, Guangchun; Levine, Andrea; Cao, Ya; Rosol, Thomas J

    2007-01-01

    Lung cancer often metastasizes to bone in patients with advanced disease. Identification of the factors involved in the interactions between lung cancer cells and bone will improve the prevention and treatment of bone metastases. We identified changes in metastasis-related gene expression of human HARA lung squamous carcinoma cells co-cultured with neonatal mouse calvariae using a pathway-specific microarray analysis. Nine genes were up-regulated and two genes down-regulated in HARA cells co-cultured with mouse calvariae. Five of the nine up-regulated genes, including caveolin 1, CD44, EphB2, ezrin, and Parathyroid hormone-related protein (PTHrP), and one down-regulated gene, SLPI, were further confirmed by Reverse transcription-polymerase chain reaction (RT-PCR). A mouse model was subsequently used to study the role of PTHrP and ezrin in bone metastasis in vivo. PTHrP (all three isoforms) and ezrin were up-regulated in HARA cells at sites of bone metastasis as detected by RT-PCR and immunohistochemistry. The PTHrP 141 mRNA isoform was increased by the greatest extent (13.9-fold) in bone metastases compared to PTHrP 139 and PTHrP 173 mRNA. We then generated a HARA cell line in which PTHrP expression was inducibly silenced by RNA interference. Silencing of PTHrP expression caused significant reduction of submembranous F-actin and decreased HARA cell invasion. Ezrin up-regulation was confirmed by Western blots on HARA cells co-cultured with adult mouse long bones. Further, Transforming growth factor beta (TGF-beta) was identified as one of the factors in the bone microenvironment that was responsible for the up-regulation of ezrin. The identification of PTHrP and ezrin as important regulators of lung cancer bone metastasis offers new mechanistic insights into the metastasis of lung cancer and provides potential targets for the prevention and treatment of lung cancer metastasis. PMID:17370040

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

    PubMed Central

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

    2011-01-01

    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

  4. Daily parathyroid hormone 1-34 replacement therapy for hypoparathyroidism induces marked changes in bone turnover and structure.

    PubMed

    Gafni, Rachel I; Brahim, Jaime S; Andreopoulou, Panagiota; Bhattacharyya, Nisan; Kelly, Marilyn H; Brillante, Beth A; Reynolds, James C; Zhou, Hua; Dempster, David W; Collins, Michael T

    2012-08-01

    Parathyroid hormone (PTH) has variable actions on bone. Chronically increased PTH is catabolic and leads to osteoporosis; yet intermittent administration is anabolic and increases bone mass. PTH deficiency is associated with decreased bone remodeling and increased bone mass. However, the effects of PTH replacement therapy on bone in hypoparathyroidism are not well known. We discontinued calcitriol therapy and treated 5 hypoparathyroid subjects (2 adults and 3 adolescents) with synthetic human PTH 1-34 (hPTH 1-34), injected two to three times daily for 18 months, with doses individualized to maintain serum calcium at 1.9 to 2.25?mmol/L. Biochemical markers and bone mineral density (BMD) were assessed every 6 months; iliac-crest biopsies were performed before and after 1 year of treatment. hPTH 1-34 therapy significantly increased bone markers to supranormal levels. Histomorphometry revealed that treatment dramatically increased cancellous bone volume and trabecular number and decreased trabecular separation. Changes in trabecular width were variable, suggesting that the increase in trabecular number was due to the observed intratrabecular tunneling. Cortical width remained unchanged; however, hPTH 1-34 treatment increased cortical porosity. Cancellous bone remodeling was also stimulated, inducing significant changes in osteoid, mineralizing surface, and bone formation rate. Similar changes were seen in endocortical and intracortical remodeling. BMD Z-scores were unchanged at the spine and femoral neck. Total hip Z-scores increased; however, total body BMD Z-scores decreased during the first 6 months of treatment and then stabilized, remaining significantly decreased compared to baseline. Radial Z-scores also decreased with treatment; this was most pronounced in the growing adolescent. Daily hPTH 1-34 therapy for hypoparathyroidism stimulated bone turnover, increased bone volume, and altered bone structure in the iliac crest. These findings suggest that treatment with hPTH 1-34 in hypoparathyroid adults and adolescents has varying effects in the different skeletal compartments, leading to an increase in trabecular bone and an apparent trabecularization of cortical bone. PMID:22492501

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

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

    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.

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

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

    The purpose of this study was to determine if human parathyroid hormone-(1-38) (hPTH(1-38)) can restore cancellous bone mass to the established osteopenic, immobilized proximal tibial metaphyses of female rats. The right hindlimbs of 6-month-old female Sprague-Dawley rats were immobilized by bandaging the right hindlimbs to the abdomen. After 30 days of right hindlimb immobilization, the rats were subcutaneously injected with 200 micrograms hPTH(1-38)/kg/day for 15 days (short-term treatment) or 75 days (longer-term treatment). Static bone histomorphometry was performed on the primary spongiosa, and both static and dynamic histomorphometry were performed on the secondary spongiosa of the right proximal tibial metaphyses. 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 in the secondary spongiosa. These changes reached a new steady state thereafter. Treatment with 200 micrograms hPTH(1-38)/kg/day for 15 days, beginning 30 days after immobilization, significantly increased trabecular bone area, thickness, and number in both primary and secondary spongiosa despite continuous immobilization when compared with controls. The short-term PTH treatment (15 days) significantly increased labeling perimeter, mineral apposition rate, and tissue referent-bone formation rate in the secondary spongiosa and stimulated longitudinal bone growth as compared with the controls. Longer PTH treatment (75 days) further increased trabecular bone area, thickness, and number as compared with controls and groups given short-term PTH treatment (15 days). The bone formation indices in the secondary spongiosa of the longer-term treated rats were lower than those of the short-term treated group, but they were still higher than those of controls. Our findings indicate that PTH treatment stimulates cancellous bone formation, and restores and adds extra cancellous bone to the established, disuse-osteopenic proximal tibial metaphysis of female rats with continuously immobilized right hindlimbs. These results suggest that PTH may be useful in treating disuse-induced osteoporosis in humans.

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

    E-print Network

    Kalueff, Allan V.

    . Neurosteroid hormone vitamin D and its utility in clinical nutrition Allan V. Kalueffa and Pentti Tuohimaab Purpose of review Vitamin D is a seco-steroid hormone with multiple functions in the nervous system. We discuss clinical and experimental evidence of the role of vitamin D in normal and pathological brain

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

    PubMed Central

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

    2015-01-01

    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

  9. Vitamin D3 metabolites and PTH synergistically stimulate bone formation of chick embryonic femur in vitro

    Microsoft Academic Search

    Hiroyoshi Endo; Mamoru Kiyoki; Kohtaro Kawashima; Tatsuyuki Naruchi; Yoshinobu Hashimoto

    1980-01-01

    Bone remodelling depends on a balance between formation and resorption. Little is known of the biological factors involved in bone formation, whereas there is much evidence that physiological factors, such as parathyroid hormone (PTH) and active metabolites of vitamin D3, influence resorption. Cells responsible for osteogenesis and osteoclasis occur in close proximity, suggesting that both might be controlled by the

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

    SciTech Connect

    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

    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.

  11. Alterations in serum parathyroid hormone and electrolyte concentrations and urinary excretion of electrolytes in horses with induced endotoxemia.

    PubMed

    Toribio, Ramiro E; Kohn, Catherine W; Hardy, Joanne; Rosol, Thomas J

    2005-01-01

    Hypocalcemia and hypomagnesemia are common in horses with sepsis and endotoxemia. We hypothesize that endotoxemia triggers a systemic inflammatory response that results in hypocalcemia and hypomagnesemia. The goal of this study was to determine the effect of endotoxin (lipopolysaccharide [LPS]) administration to healthy horses on serum parathyroid hormone (PTH), ionized calcium (Ca2+) and total calcium (tCa), ionized magnesium (Mg2+) and total magnesium (tMg), phosphate (Pi), potassium (K+), sodium (Na+), chloride (Cl-), and insulin concentrations, and on the urinary excretion of these electrolytes. Twelve mares were infused with Escherichia coli LPS (30 ng/kg/h i.v.) for 1 hour. Six mares were infused with saline (controls). In LPS-infused horses, heart rate increased significantly from (mean +/- SD) 40.0 +/- 1.3 to 70.0 +/- 9.0 beats/min, respiratory rate from 12.7 +/- 1.0 to 21.1 +/- 3.0 breaths/min, body temperature from 37.4 +/- 0.3 to 38.9 +/- 0.6 degrees C, and tumor necrosis factor-alpha concentrations from 6.6 +/- 3.5 to 507 +/- 260 pg/mL (P < .05). White blood cell count decreased significantly from 7570 +/- 600 to 1960 +/- 560 cells/ microL. Serum concentrations of Ca2+ decreased from 6.5 +/- 0.3 to 6.0 +/- 0.3 mg/dL, of Mg2+ from 0.53 +/- 0.06 to 0.43 +/- 0.04 mM, of tMg from 0.78 +/- 0.05 to 0.62 +/- 0.08 mM, of K+ from 4.3 +/- 0.4 to 3.0 +/- 0.5 mEq/L, and of Pi from 3.4 +/- 0.5 to 1.7 +/- 0.5 mg/dL (all P < .05). PTH increased significantly from 1.3 +/- 0.4 to 6.0 +/- 5.2 pM; however, in some horses (n=2), PTH did not increase despite hypocalcemia. Insulin increased significantly from 9.4 +/- 3.6 to 50.5 +/- 9.6 microIU/mL (n=3). Urinary fractional excretion of Ca2+ decreased significantly from 4.7 +/- 1.4 to 1.7 +/- 1.2%, of Mg2+ from 36.6 +/- 6.5 to 11.7 +/- 7.3%, and of K+ from 37.9 +/- 11.3 to 17.7 +/- 6.2%. Fractional excretion of Pi increased from 0.02 +/- 0.02 to 0.14 +/- 0.07% and of Na+ from 0.26 +/- 0.13% to 1.2 +/- 0.5%. No changes were found in serum tCa, Na+, and Cl- concentrations. In conclusion, endotoxemia in horses resulted in electrolyte abnormalities that included hypocalcemia, hypomagnesemia, hypokalemia, hypophosphatemia, and increased serum PTH and insulin concentrations. PMID:15822568

  12. The development of a bone- and parathyroid-specific analog of vitamin D: 2-methylene-19-Nor-(20S)-1?,25-dihydroxyvitamin D3

    PubMed Central

    DeLuca, Hector F

    2014-01-01

    The goal of synthetic chemists in the vitamin D field has been to produce an analog(s) of 1?,25-dihydroxyvitamin D3 (1,25-(OH)2D3) that is selective for a specific function. The accumulation of structure/function information has led to the synthesis of two analogs that are both selective and more potent than 1,25-(OH)2D3, that is, 2-methylene-19-nor-(20S)-1?,25-dihydroxyvitamin D3 (2MD) and 2?-methyl-19-nor-(20S)-1?,25-dihydroxyvitamin D3 (2AMD). In vivo, the efficacy of 2MD is approximately equal to that of 1,25-(OH)2D3 in intestinal calcium transport but is 30- to 100-fold more active in bone mobilization. In vitro, 2MD supports new bone synthesis at 10?12?M, whereas 1,25-(OH)2D3 is active at 10?8?M. Similarly, 2MD is two orders of magnitude more potent than 1,25-(OH)2D3 in stimulating osteoclastogenesis and osteoclastic bone resorption. 2MD also markedly increases bone mass and bone strength of ovariectomized female rats. In postmenopausal women, 2MD significantly increases markers of both bone formation and resorption but has minimal effect on bone mass. Thus, in patients who are undergoing primarily remodeling rather than modeling (rat), the increased resorption largely counteracts the increased bone formation. So far, 2MD has not been tested for reduction of fractures in this population. However, its selectivity includes the parathyroid gland. Thus in the 5/6-nephrectomy model of chronic renal failure, 2MD is much more potent than currently available vitamin D compounds used to suppress secondary hyperparathyroidism of renal failure without causing hypercalcemia. It is currently in phase 2B trials in patients on dialysis. PMID:24818006

  13. The role of vitamin D in malaria.

    PubMed

    L??ng, Khanh Vinh Qu?c; Nguy?n, Lan Thi Hoŕng

    2015-01-01

    An abnormal calcium-parathyroid hormone (PTH)-vitamin D axis has been reported in patients with malaria infection. A role for vitamin D in malaria has been suggested by many studies. Genetic studies have identified numerous factors that link vitamin D to malaria, including human leukocyte antigen genes, toll-like receptors, heme oxygenase-1, angiopoietin-2, cytotoxic T lymphocyte antigen-4, nucleotide-binding oligomerization domain-like receptors, and Bcl-2. Vitamin D has also been implicated in malaria via its effects on the Bacillus Calmette-Guerin (BCG) vaccine, matrix metalloproteinases, mitogen-activated protein kinase pathways, prostaglandins, reactive oxidative species, and nitric oxide synthase. Vitamin D may be important in malaria; therefore, additional research on its role in malaria is needed. PMID:25596566

  14. Vitamin D–Binding Protein and Vitamin D Status of Black Americans and White Americans

    PubMed Central

    Powe, Camille E.; Evans, Michele K.; Wenger, Julia; Zonderman, Alan B.; Berg, Anders H.; Nalls, Michael; Tamez, Hector; Zhang, Dongsheng; Bhan, Ishir; Karumanchi, S. Ananth; Powe, Neil R.; Thadhani, Ravi

    2014-01-01

    Background Low levels of total 25-hydroxyvitamin D are common among black Americans. Vitamin D–binding protein has not been considered in the assessment of vitamin D deficiency. Methods In the Healthy Aging in Neighborhoods of Diversity across the Life Span cohort of blacks and whites (2085 participants), we measured levels of total 25-hydroxyvitamin D, vitamin D–binding protein, and parathyroid hormone as well as bone mineral density (BMD). We genotyped study participants for two common polymorphisms in the vitamin D–binding protein gene (rs7041 and rs4588). We estimated levels of bioavailable 25-hydroxyvitamin D in homozygous participants. Results Mean (±SE) levels of both total 25-hydroxyvitamin D and vitamin D–binding protein were lower in blacks than in whites (total 25-hydroxyvitamin D, 15.6±0.2 ng per milliliter vs. 25.8±0.4 ng per milliliter, P<0.001; vitamin D–binding protein, 168±3 ?g per milliliter vs. 337±5 ?g per milliliter, P<0.001). Genetic polymorphisms independently appeared to explain 79.4% and 9.9% of the variation in levels of vitamin D–binding protein and total 25-hydroxyvitamin D, respectively. BMD was higher in blacks than in whites (1.05±0.01 g per square centimeter vs. 0.94±0.01 g per square centimeter, P<0.001). Levels of parathyroid hormone increased with decreasing levels of total or bioavailable 25-hydroxyvitamin D (P<0.001 for both relationships), yet within each quintile of parathyroid hormone concentration, blacks had significantly lower levels of total 25-hydroxyvitamin D than whites. Among homozygous participants, blacks and whites had similar levels of bioavailable 25-hydroxy vitamin D overall (2.9±0.1 ng per milliliter and 3.1±0.1 ng per milliliter, respectively; P = 0.71) and within quintiles of parathyroid hormone concentration. Conclusions Community-dwelling black Americans, as compared with whites, had low levels of total 25-hydroxyvitamin D and vitamin D–binding protein, resulting in similar concentrations of estimated bioavailable 25-hydroxyvitamin D. Racial differences in the prevalence of common genetic polymorphisms provide a likely explanation for this observation. (Funded by the National Institute on Aging and others.) PMID:24256378

  15. Bone tissue and its mineralization in aged estrogen-depleted rats after long-term intermittent treatment with parathyroid hormone (PTH) analog SDZ PTS 893 or human PTH(1-34)

    Microsoft Academic Search

    M Kneissel; A Boyde; J. A Gasser

    2001-01-01

    Intermittently administered parathyroid hormone (PTH) is a potent bone anabolic agent. We aimed to determine the impact of long-term treatment with PTH on bone structure, dynamics, and mineralization. We ovariectomized (ovx) 1-year-old rats with the exception of a baseline and a sham-operated group. Twelve weeks later, a 36 week treatment with PTH analog SDZ PTS 893 (12.5, 25, 50, 100

  16. Duplicated zebrafish co-orthologs of parathyroid hormone-related peptide (PTHrP, Pthlh) play different roles in craniofacial skeletogenesis.

    PubMed

    Yan, Yi-Lin; Bhattacharya, Poulomi; He, Xin Jun; Ponugoti, Bhaskar; Marquardt, Ben; Layman, Jason; Grunloh, Melissa; Postlethwait, John H; Rubin, David A

    2012-09-01

    In mammals, parathyroid hormone-related peptide (PTHrP, alias PTH-like hormone (Pthlh)) acts as a paracrine hormone that regulates the patterning of cartilage, bone, teeth, pancreas, and thymus. Beyond mammals, however, little is known about the molecular genetic mechanisms by which Pthlh regulates early development. To evaluate conserved pathways of craniofacial skeletogenesis, we isolated two Pthlh co-orthologs from the zebrafish (Danio rerio) and investigated their structural, phylogenetic, and syntenic relationships, expression, and function. Results showed that pthlh duplicates originated in the teleost genome duplication. Zebrafish pthlha and pthlhb were maternally expressed and showed overlapping and distinct zygotic expression patterns during skeletal development that mirrored mammalian expression domains. To explore the regulation of duplicated pthlh genes, we studied their expression patterns in mutants and found that both sox9a and sox9b are upstream of pthlha in arch and fin bud cartilages, but only sox9b is upstream of pthlha in the pancreas. Morpholino antisense knockdown showed that pthlha regulates both sox9a and sox9b in the pharyngeal arches but not in the brain or otic vesicles and that pthlhb does not regulate either sox9 gene, which is likely related to its highly degraded nuclear localization signal. Knockdown of pthlha but not pthlhb caused runx2b overexpression in craniofacial cartilages and premature bone mineralization. We conclude that in normal cartilage development, sox9 upregulates pthlh, which downregulates runx2, and that the duplicated nature of all three of these genes in zebrafish creates a network of regulation by different co-orthologs in different tissues. PMID:22761277

  17. Calciotrophic hormones and hyperglycemia modulate vitamin D receptor and 25 hydroxyy vitamin D 1-? hydroxylase mRNA expression in human vascular smooth muscle cells.

    PubMed

    Somjen, D; Knoll, E; Sharon, O; Many, A; Stern, N

    2015-04-01

    Estrogen receptors (ER? and ER?), the vitamin D receptor (VDR) and 25 hydroxyy vitamin D 1-? hydroxylase (1OHase) mRNA are expressed in vascular smooth muscle cells (VSMC). In these cells estrogenic hormones modulate cell proliferation as measured by DNA synthesis (DNA). In the present study we determined whether or not the calciotrophic hormones PTH 1-34 (PTH) and less- calcemic vitamin D analog QW as well as hyperglycemia can regulate DNA synthesis and CK. E2 had a bimodal effect on VSMC DNA synthesis, such that proliferation was inhibited at 30nM but stimulated at 0.3nM. PTH at 50nM increased, whereas QW at 10nM inhibited DNA synthesis. Hyperglycemia inhibited the effects on high E2, QW and PTH on DNA only. Both QW and PTH increased ER? mRNA expression, but only PTH increased ER? expression. Likewise, both PTH and QW stimulated VDR and 1OHase expression and activity. ER?, VDR and 1OHase expression and activity were inhibited by hyperglycemia, but ER? expression was unaffected by hyperglycemia. In conclusion, calcitrophic hormones modify VSMC growth and concomitantly affect ER expression in these cells as well as the endogenous VSMC vitamin D system elements, including VDR and 1OHase. Some of the later changes may likely participate in growth effects. Of importance in the observation is that several regulatory effects are deranged in the presence of hyperglycemia, particularly the PTH- and vitamin D-dependent up regulation of VDR and 1OHase in these cells. The implications of these effects require further studies. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. PMID:25448744

  18. Vitamin D, and Kidney Disease

    PubMed Central

    Kim, Hyung Soo; Chung, Wookyung

    2011-01-01

    Mineral metabolism abnormalities, such as low 1,25-dihydroxyvitamin D (1,25(OH)2D) and elevated parathyroid hormone (PTH), are common at even higher glomerular filtration rate than previously described. Levels of 25-hydroxyvitamin D (25(OH)D) show an inverse correlation with those of intact PTH and phosphorus. Studies of the general population found much higher all-cause and cardiovascular (CV) mortality for patients with lower levels of vitamin D; this finding suggests that low 25(OH)D level is a risk factor and predictive of CV events in patients without chronic kidney disease (CKD). 25(OH)D/1,25(OH)2D becomes deficient with progression of CKD. Additionally, studies of dialysis patients have found an association of vitamin D deficiency with increased mortality. Restoration of the physiology of vitamin D receptor activation should be essential therapy for CKD patients. PMID:21998600

  19. 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

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

    2007-01-01

    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

  20. Replantation with cryopreserved parathyroid for permanent hypoparathyroidism: a case report and review of literatures

    PubMed Central

    Liu, Hai-Guang; Chen, Zai-Chong; Zhang, Xiao-Hua; Yang, Kai

    2015-01-01

    Permanent postsurgical hypoparathyroidism is defined as insufficient parathyroid hormone (PTH) to maintain normocalcemia 6 months after surgery. It occurs mostly in reoperation for persistent or recurrent hyperparathyroidism. The treatment of long-term calcium and vitamin D supplement is burdensome and may cause iatrogenic complications. PTH replacement is potential but still under trials. Only replantation with cryopreserved parathyroid is an available treatment for patients to reduce or stop long-term drug administration. However, this treatment is not applied widely in developing countries, due to lack of experiences and skills. Herein, we reported a 58-year-old male presented a continuous elevated parathyroid hormone up to about 2342 ng/L and bone pain during hemodialysis for 6 years due to chronic renal failure. He underwent the first operation total parathyroidectomy and autotransplantation. After this operation, he suffered from a persistent calcemia and permanent hypoparathyroidism. After three times of replantation with cryopreserved parathyroid and dialysis with a high calcium dialysate, the low concentration of calcium was elevated and symptoms of hypocalcemia disappeared. However, PTH was not elevated significantly in the long term. It might be related to our nonstandard cryopreservation protocol and no microbiological and histological examinations before replantation, compared with other successful reports. Therefore, we suggest a standard cryopreservation protocol should be followed by non-experienced institutions, especially in developing countries. Furthermore, a high calcium dialysate is efficient to increase calcium concentration and alleviate symptoms of hypocalcemia. It may be an available treatment of persistent hypocalcemia and permanent hypoparathyroidism in dialysis patients.

  1. Amphibian parathyroids: morphological and functional aspects.

    PubMed

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

    1995-10-01

    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

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

    NSDL National Science Digital Library

    2002-01-01

    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.

  3. VITAMINS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamins are organic compounds that are essential to life. They function as metabolic catalysts or regulators and can generally be classified on the basis of their solubility as fat-soluble vitamins or water-soluble vitamins. All of the vitamins are required for normal function in all animals and ...

  4. Parathyroid hormone increases the concentration of insulin-like growth factor-I and transforming growth factor beta 1 in rat bone.

    PubMed Central

    Pfeilschifter, J; Laukhuf, F; Müller-Beckmann, B; Blum, W F; Pfister, T; Ziegler, R

    1995-01-01

    Intermittent treatment with parathyroid hormone (PTH) increases bone mass in experimental animals and humans. In vitro studies have suggested that the anabolic effect of PTH may be mediated by local growth factors. However, the relevance of these findings to in vivo situations remains unclear. In this study, we examined a time course of daily s.c. injections of hPTH (1-34) on the skeletal concentration of insulin-like growth factor (IGF)-I, IGF-II, and transforming growth factor beta (TGF-beta) in the proximal tail vertebrae of male rats. PTH caused a time and dose-dependent increase in the bone mineral density of the lumbar spine. This anabolic effect on bone mass was accompanied by progressive increases in bone matrix-associated IGF-I and TGF-beta 1. Increases in IGF-I and TGF-beta 1 became apparent after four and eight weeks of PTH treatment respectively and persisted through week 12. PTH had no effect on circulating IGF-I, suggesting that the increase of bone matrix IGF-I was due to the local effect of PTH on bone tissue directly rather than to an increase of circulating IGF-I. These data are consistent with the hypothesis that IGF-I and TGF-beta 1 may play a role as local mediators of the anabolic effects of PTH on bone metabolism. PMID:7635970

  5. AU-RICH ELEMENTS IN THE 3?-UTR REGULATE THE STABILITY OF THE 141 AMINO ACID ISOFORM OF PARATHYROID HORMONE-RELATED PROTEIN mRNA

    PubMed Central

    Luchin, Alexander I.; Nadella, Murali V.P.; Thudi, Nanda K.; Dirksen, Wessel P.; Gulati, Parul; Fernandez, Soledad A.; Rosol, Thomas J.

    2012-01-01

    We demonstrated previously that parathyroid hormone-related protein (PTHrP) 1-141 mRNA is the least stable of three isoforms and is the only isoform that is stabilized by TGF-?. In order to understand how PTHrP mRNA is stabilized by TGF-?, we first sought to elucidate the mechanism(s) that are responsible for the instability of PTHrP isoform 1-141 mRNA. The 3?-UTR of isoform 1-141 contains four AU-rich elements (AREs), which are known to mediate mRNA degradation. We utilized a luciferase reporter system to test whether these four AREs are responsible for the short half-life of PTHrP 1-141 mRNA. Our results demonstrated that ARE elements in the 3?-UTR of PTHrP 1-141 mRNA play a significant role in regulation of the stability of the mRNA. It is known that AREs mediate their effects on mRNA stability through a number of ARE-binding proteins that recruit the exosome, a complex of exonucleases that degrades the mRNA. We identified tristetraproline (TTP) as an RNA-binding protein that may be involved in ARE-mediated degradation of PTHrP 1-141 mRNA. PMID:22960231

  6. AU-rich elements in the 3'-UTR regulate the stability of the 141 amino acid isoform of parathyroid hormone-related protein mRNA.

    PubMed

    Luchin, Alexander I; Nadella, Murali V P; Thudi, Nanda K; Dirksen, Wessel P; Gulati, Parul; Fernandez, Soledad A; Rosol, Thomas J

    2012-11-25

    We demonstrated previously that parathyroid hormone-related protein (PTHrP) 1-141 mRNA is the least stable of three isoforms and is the only isoform that is stabilized by TGF-?. In order to understand how PTHrP mRNA is stabilized by TGF-?, we first sought to elucidate the mechanism(s) that are responsible for the instability of PTHrP isoform 1-141 mRNA. The 3'-UTR of isoform 1-141 contains four AU-rich elements (AREs), which are known to mediate mRNA degradation. We utilized a luciferase reporter system to test whether these four AREs are responsible for the short half-life of PTHrP 1-141 mRNA. Our results demonstrated that ARE elements in the 3'-UTR of PTHrP 1-141 mRNA play a significant role in regulation of the stability of the mRNA. It is known that AREs mediate their effects on mRNA stability through a number of ARE-binding proteins that recruit the exosome, a complex of exonucleases that degrades the mRNA. We identified tristetraproline (TTP) as an RNA-binding protein that may be involved in ARE-mediated degradation of PTHrP 1-141 mRNA. PMID:22960231

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

    PubMed Central

    2009-01-01

    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

  8. [A case of hypercalcemia associated with parathyroid hormone-related protein produced by the recurrence of B-cell lymphoma of the pancreas].

    PubMed

    Iida, Tomoya; Satoh, Shuji; Kaneto, Hiroyuki; Sasaki, Hajime; Naganawa, Yumiko; Ishigami, Keisuke; Nakagaki, Suguru; Shimizu, Haruo; Konishi, Yasuhiro; Kon, Shinichiro

    2014-11-01

    An 87-year-old woman was diagnosed with primary diffuse large B-cell lymphoma of the pancreas by endoscopic ultrasonography-guided fine needle aspiration. Complete remission was achieved after treatment with six courses of R-CHOP chemotherapy. However, two and a half years later, she was readmitted because of weakness during walking. At this time, laboratory tests revealed hypercalcemia associated with high plasma levels of parathyroid hormone-related protein (PTHrP), but bone lesions were not detected. Although computed tomography only revealed splenomegaly, we suspected a recurrence of her malignant lymphoma because she also had marked elevation of soluble interleukin-2 receptor and lactate dehydrogenase levels. Bone marrow examination revealed the involvement of Burkitt's lymphoma cells with malignant transformation. Immunohistochemical analysis confirmed that hypercalcemia was caused by a paraneoplastic syndrome related to PTHrP-producing B-cell lymphoma cells. Unfortunately, the patient's general condition rapidly deteriorated, and she died soon after admission. Our case is unusual because of the presentation of bone marrow relapse of malignant lymphoma. PMID:25373378

  9. Nuclear translocation of ?-catenin mediates the parathyroid hormone-induced endothelial-to-mesenchymal transition in human renal glomerular endothelial cells.

    PubMed

    Wu, Min; Tang, Ri-Ning; Liu, Hong; Ma, Kun-Ling; Lv, Lin-Li; Liu, Bi-Cheng

    2014-10-01

    Emerging evidence shows that increased parathyroid hormone (PTH) accelerates endothelial injury and subsequent organ fibrosis. Although the underlying mechanisms remain largely unknown, the endothelial-to-mesenchymal transition (EndMT) has recently been demonstrated to be a crucial event during fibrotic disorders. Therefore, the present study aimed to investigate whether elevated PTH could induce EndMT in primary human renal glomerular endothelial cells (GECs) and to determine the possible underlying signaling pathway. The expression of EndMT-related markers was determined by real-time PCR, Western blotting, and confocal microscopy. The results showed that PTH receptor (PTHR) was expressed in GECs and its expression was decreased by increasing concentration of PTH. Moreover, PTH significantly inhibited the expression of endothelial marker CD31 and increased the expression of mesenchymal markers FSP1 and ?-SMA in concentration- and time-dependent manners. Confocal microscopy revealed an increasing overlap of CD31 with FSP1 in some GECs after PTH treatment. The expression of type I collagen was upregulated by PTH. Furthermore, PTH enhanced the nuclear ?-catenin protein levels, and decreased cytoplasmic ?-catenin expression in GECs was observed. In contrast, DKK1, an inhibitor of ?-catenin nuclear translocation, attenuated such changes in EndMT-related markers induced by PTH. In summary, these data demonstrated that elevated PTH-induced EndMT in human GECs might be partially mediated by the nuclear translocation of ?-catenin. PMID:24821601

  10. Parathyroid hormone blocks the stimulatory effect of insulin-like growth factor-I on collagen synthesis in cultured 21-day fetal rat calvariae

    SciTech Connect

    Kream, B.E.; Petersen, D.N.; Raisz, L.G. (Univ. of Connecticut Health Center, Farmington (USA))

    1990-01-01

    We examined the interaction of parathyroid hormone (PTH) and recombinant human insulin-like growth factor I (IGF-I) on collagen synthesis in 21-day fetal rat calvariae as assessed by measuring the incorporation of ({sup 3}H)proline into collagenase-digestible protein. After 96 hours of culture, 10 nM PTH antagonized the stimulation of collagen synthesis and partially blocked the increase in dry weight produced by 10 nM IGF-I. The effect of PTH to block IGF-I stimulated collagen synthesis was observed in the central bone of calvariae and was mimicked by forskolin and phorbol 12-myristate 13-acetate, but not by 1,25-dihydroxyvitamin D3, transforming growth factor-alpha or dexamethasone. Our data are consistent with the concept that the direct effect of PTH is to inhibit basal CDP labeling and fully oppose IGF-I stimulated CDP labeling. The finding that this effect of PTH is mimicked by forskolin and PMA suggests that this block in IGF-I stimulation of CDP labeling involves both cAMP and protein kinase C mediated pathways.

  11. An evaluation of several biochemical markers for bone formation and resorption in a protocol utilizing cyclical parathyroid hormone and calcitonin therapy for osteoporosis.

    PubMed Central

    Hodsman, A B; Fraher, L J; Ostbye, T; Adachi, J D; Steer, B M

    1993-01-01

    Female patients (n = 20) with osteoporosis, aged 66 +/- 5 yr were studied during a 24-h infusion of parathyroid hormone (PTH [1-34]) at a rate of 0.5 IU equivalents/kg.h, and then during a 28-d period of subcutaneous injections, at a dose of 800 IU equivalents per day. Thereafter half the patients received subcutaneous injections of calcitonin, 75 U/d for 42 d, and all patients were followed to the end of a 90-d cycle. Biochemical markers of bone formation (serum alkaline phosphatase, osteocalcin, and the carboxy-terminal extension peptide of pro-collagen 1) and bone resorption (fasting urine calcium, hydroxyproline, and deoxypyridinoline) were compared during treatment by the intravenous and subcutaneous route of PTH administration, and subsequently during calcitonin therapy. During intravenous PTH infusion there were significant reductions in all three bone formation markers, despite expected rises in urinary calcium and hydroxyproline. By contrast, the circulating markers of bone formation increased rapidly by > 100% of baseline values during daily PTH injections (P < 0.001). Significant increases in bone resorption markers were only seen at the end of the 28 d of injections, but were < 100% over baseline values, (P < 0.05). Quantitative bone histomorphometry from biopsies obtained after 28 d of PTH treatment confirmed that bone formation at both the cellular and tissue levels were two to five times higher than similar indices measured in a control group of biopsies from untreated osteoporotic women. Subsequent treatment of these patients with calcitonin showed no significant changes in the biochemical markers of bone formation and only a modest attenuation of bone resorption. Thus, PTH infusion may inhibit bone formation, as judged by circulating biochemical markers, whereas daily injections confirm the potent anabolic actions of the hormone. Sequential calcitonin therapy does not appear to act synergistically with PTH in cyclical therapeutic protocols. PMID:8450043

  12. Klotho Lacks a Vitamin D Independent Physiological Role in Glucose Homeostasis, Bone Turnover, and Steady-State PTH Secretion In Vivo

    Microsoft Academic Search

    René Anour; Olena Andrukhova; Eva Ritter; Ute Zeitz; Reinhold G. Erben

    2012-01-01

    Apart from its function as co-receptor for fibroblast growth factor-23 (FGF23), Klotho is thought to regulate insulin signaling, intracellular oxidative stress, and parathyroid hormone (PTH) secretion in an FGF23 independent fashion. Here, we crossed Klotho deficient (Kl?\\/?) mice with vitamin D receptor (VDR) mutant mice to examine further vitamin D independent functions of Klotho. All mice were fed a rescue

  13. AXT914 a novel, orally-active parathyroid hormone-releasing drug in two early studies of healthy volunteers and postmenopausal women.

    PubMed

    John, Markus R; Harfst, Evita; Loeffler, Juergen; Belleli, Rossella; Mason, June; Bruin, Gerard J M; Seuwen, Klaus; Klickstein, Lloyd B; Mindeholm, Linda; Widler, Leo; Kneissel, Michaela

    2014-07-01

    Antagonism of the calcium-sensing receptor in the parathyroid gland leads to parathyroid hormone (PTH) release. Calcilytics are a new class of molecules designed to exploit this mechanism. In order to mimic the known bone-anabolic pharmacokinetic (PK) profile of s.c. administered PTH, such molecules must trigger sharp, transient and robust release of PTH. The results of two early clinical studies with the orally-active calcilytic AXT914, a quinazolin-2ne derivative are reported. These were GCP-compliant, single and multiple dose studies of PK/PD and tolerability in healthy volunteers and postmenopausal women. The first study, examined single ascending doses (4 to 120 mg) and limited multiple doses (60 or 120 mgq.d. for 12 days) of AXT914. The second study was a randomized, double-blind, active- and placebo-controlled, 4-week repeat-dose parallel group study of healthy postmenopausal women (45 and 60 mg AXT914, placebo, 20 ?g Forteo/teriparatide/PTH(1-34) fragment). AXT914 was well tolerated at all doses and reproducibly induced the desired PTH-release profiles. Yet, 4 weeks of 45 or 60 mg AXT914 did not result in the expected changes in circulating bone biomarkers seen with teriparatide. However total serum calcium levels increased above baseline in the 45 and 60 mg AXT914 treatment groups (8.0% and 10.7%, respectively), compared to that in the teriparatide and placebo groups (1.3% and 1.0%, respectively). Thus the trial was terminated after a planned interim analysis due to lack of effect on bone formation biomarkers and dose-limiting effects on serum calcium. In conclusion, AXT914 was well tolerated but the observed transient and reproducible PTH-release after repeat oral administration of AXT914 which showed an exposure profile close to that of s c. PTH, did not translate into a bone anabolic response and was associated with a persistent dose-related increase in serum calcium concentrations. PMID:24769332

  14. Parathyroid adenocarcinoma.

    PubMed Central

    Nazem, A.; Anderson, B.; Leffal, L. D.; Reghini, M.; Brown, J.

    1989-01-01

    Parathyroid adenocarcinoma is a very rare carcinoma with an equal male-female incidence. The clinical picture that adenocarcinoma of the parathyroid presents is the same as that of hyperparathyroidism due to adenoma. Onset of parathyroid adenocarcinoma occurs primarily in the fourth decade of life. It is not incompatible with long-term survival provided that the entire gland is removed at the initial operation without rupture of the capsule. If the carcinoma recurs, it grows slowly and any spread tends to be local. Distant metastasis is rare. Calcium levels above 13 mg/100 mL should alert the clinician to the possibility of adenocarcinoma of the parathyroid. Increased mitotic figures, increased fibrosis of the gland, and invasion of the vessels and surrounding tissues are the features indicative of malignancy. A review of the literature reveals that fewer than 150 cases of this entity have been reported. The authors present two case reports and discuss the epidemiology, clinical picture, pathology, and therapy of parathyroid adenocarcinoma. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:2666678

  15. Relationship between vitamin D deficiency and cardiovascular disease

    PubMed Central

    Ku, Yan-Chiou; Liu, Mu-En; Ku, Chang-Sheng; Liu, Ta-Yuan; Lin, Shoa-Lin

    2013-01-01

    Epidemiological studies have found that low 25-hydroxyvitamin D levels may be associated with coronary risk factors and adverse cardiovascular outcomes. Additionally, vitamin D deficiency causes an increase in parathyroid hormone, which increases insulin resistance and is associated with diabetes, hypertension, inflammation, and increased cardiovascular risk. In this review, we analyze the association between vitamin D supplementation and the reduction in cardiovascular disease. The role of vitamin D deficiency in cardiovascular morbidity and mortality is still controversial, and larger scale, randomized placebo controlled trials are needed to investigate whether oral vitamin D supplementation can reduce cardiovascular risk. Given the low cost, safety, and demonstrated benefit of higher 25-hydroxyvitamin D levels, vitamin D supplementation should become a public health priority for combating common and costly chronic cardiovascular diseases. PMID:24109497

  16. Severe myopathy associated with vitamin D deficiency in western New York.

    PubMed

    Prabhala, A; Garg, R; Dandona, P

    2000-04-24

    Five cases of severe myopathy associated with vitamin D deficiency are described. Each patient was confined to a wheelchair because of weakness and immobility. Two were elderly, 1 was a 37-year-old African American with type 1 diabetes mellitus, 1 was being treated for carcinoid syndrome, and 1 was severely malnourished due to poor oral intake. In each, weakness had previously been attributed to other causes, including old age, concomitant diabetic neuropathy, or general debility. Correct diagnosis was made initially by a high index of suspicion, following the demonstration of clinical proximal myopathy; confirmation was made by the demonstration of low 25-hydroxyvitamin D and elevated parathyroid hormone concentrations. Treatment with vitamin D caused a resolution of body aches and pains and a restoration of normal muscle strength in 4 to 6 weeks. Four patients became fully mobile and had normal 25-hydroxyvitamin D concentrations, and the fifth also became mobile. In the 4 fully recovered cases, parathyroid hormone levels on follow-up were lower but still elevated. This finding suggests a degree of autonomy of parathyroid secretion known to occur in cases of long-standing vitamin D deficiency. Myopathy, due to chronic vitamin D deficiency, probably contributes to immobility and ill health in a significant number of patients in the northern United States. An awareness of this condition may significantly improve mobility and quality of life in patient populations vulnerable to vitamin D deficiency. PMID:10789615

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

    SciTech Connect

    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

    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.

  18. Parathyroid Hormone-responsive Smad3-related Factor, Tmem119, Promotes Osteoblast Differentiation and Interacts with the Bone Morphogenetic Protein-Runx2 Pathway*

    PubMed Central

    Hisa, Itoko; Inoue, Yoshifumi; Hendy, Geoffrey N.; Canaff, Lucie; Kitazawa, Riko; Kitazawa, Sohei; Komori, Toshihisa; Sugimoto, Toshitsugu; Seino, Susumu; Kaji, Hiroshi

    2011-01-01

    The mechanisms whereby the parathyroid hormone (PTH) exerts its anabolic action on bone are incompletely understood. We previously showed that inhibition of ERK1/2 enhanced Smad3-induced bone anabolic action in osteoblasts. These findings suggested the hypothesis that changes in gene expression associated with the altered Smad3-induced signaling brought about by an ERK1/2 inhibitor would identify novel bone anabolic factors in osteoblasts. We therefore performed a comparative DNA microarray analysis between empty vector-transfected mouse osteoblastic MC3T3-E1 cells and PD98059-treated stable Smad3-overexpressing MC3T3-E1 cells. Among the novel factors, Tmem119 was selected on the basis of its rapid induction by PTH independent of later increases in endogenous TGF-?. The levels of Tmem119 increased with time in cultures of MC3T3-E1 cells and mouse mesenchymal ST-2 cells committed to the osteoblast lineage by BMP-2. PTH stimulated Tmem119 levels within 1 h as determined by Western blot analysis and immunocytochemistry in MC3T3-E1 cells. MC3T3-E1 cells stably overexpressing Tmem119 exhibited elevated levels of Runx2, osteocalcin, alkaline phosphatase, and ?-catenin, whereas Tmem119 augmented BMP-2-induced Runx2 levels in mesenchymal cells. Tmem119 interacted with Runx2, Smad1, and Smad5 in C2C12 cells. In conclusion, we identified a Smad3-related factor, Tmem119, that is induced by PTH and promotes differentiation in mouse osteoblastic cells. Tmem119 is an important molecule in the pathway downstream of PTH and Smad3 signaling in osteoblasts. PMID:21239498

  19. Parathyroid hormone-responsive Smad3-related factor, Tmem119, promotes osteoblast differentiation and interacts with the bone morphogenetic protein-Runx2 pathway.

    PubMed

    Hisa, Itoko; Inoue, Yoshifumi; Hendy, Geoffrey N; Canaff, Lucie; Kitazawa, Riko; Kitazawa, Sohei; Komori, Toshihisa; Sugimoto, Toshitsugu; Seino, Susumu; Kaji, Hiroshi

    2011-03-18

    The mechanisms whereby the parathyroid hormone (PTH) exerts its anabolic action on bone are incompletely understood. We previously showed that inhibition of ERK1/2 enhanced Smad3-induced bone anabolic action in osteoblasts. These findings suggested the hypothesis that changes in gene expression associated with the altered Smad3-induced signaling brought about by an ERK1/2 inhibitor would identify novel bone anabolic factors in osteoblasts. We therefore performed a comparative DNA microarray analysis between empty vector-transfected mouse osteoblastic MC3T3-E1 cells and PD98059-treated stable Smad3-overexpressing MC3T3-E1 cells. Among the novel factors, Tmem119 was selected on the basis of its rapid induction by PTH independent of later increases in endogenous TGF-?. The levels of Tmem119 increased with time in cultures of MC3T3-E1 cells and mouse mesenchymal ST-2 cells committed to the osteoblast lineage by BMP-2. PTH stimulated Tmem119 levels within 1 h as determined by Western blot analysis and immunocytochemistry in MC3T3-E1 cells. MC3T3-E1 cells stably overexpressing Tmem119 exhibited elevated levels of Runx2, osteocalcin, alkaline phosphatase, and ?-catenin, whereas Tmem119 augmented BMP-2-induced Runx2 levels in mesenchymal cells. Tmem119 interacted with Runx2, Smad1, and Smad5 in C2C12 cells. In conclusion, we identified a Smad3-related factor, Tmem119, that is induced by PTH and promotes differentiation in mouse osteoblastic cells. Tmem119 is an important molecule in the pathway downstream of PTH and Smad3 signaling in osteoblasts. PMID:21239498

  20. P38 Mitogen-Activated Protein Kinase Inhibitor, FR167653, Inhibits Parathyroid Hormone Related Protein-Induced Osteoclastogenesis and Bone Resorption

    PubMed Central

    Nishikawa, Masataka; Yoshikawa, Hideki; Myoui, Akira

    2011-01-01

    p38 mitogen-activated protein kinase (MAPK) acts downstream in the signaling pathway that includes receptor activator of NF-?B (RANK), a powerful inducer of osteoclast formation and activation. We investigated the role of p38 MAPK in parathyroid hormone related protein (PTHrP)-induced osteoclastogenesis in vitro and PTHrP-induced bone resorption in vivo. The ability of FR167653 to inhibit osteoclast formation was evaluated by counting the number of tartrate-resistant acid phosphatase positive multinucleated cells (TRAP-positive MNCs) in in vitro osteoclastgenesis assays. Its mechanisms were evaluated by detecting the expression level of c-Fos and nuclear factor of activated T cells c1 (NFATc1) in bone marrow macrophages(BMMs) stimulated with sRANKL and M-CSF, and by detecting the expression level of osteoprotegerin (OPG) and RANKL in bone marrow stromal cells stimulated with PTHrP in the presence of FR167653. The function of FR167653 on bone resorption was assessed by measuring the bone resorption area radiographically and by counting osteoclast number per unit bone tissue area in calvaria in a mouse model of bone resorption by injecting PTHrP subcutaneously onto calvaria. Whole blood ionized calcium levels were also recorded. FR167653 inhibited PTHrP-induced osteoclast formation and PTHrP-induced c-Fos and NFATc1 expression in bone marrow macrophages, but not the expression levels of RANKL and OPG in primary bone marrow stromal cells treated by PTHrP. Furthermore, bone resorption area and osteoclast number in vivo were significantly decreased by the treatment of FR167653. Systemic hypercalcemia was also partially inhibited. Inhibition of p38 MAPK by FR167653 blocks PTHrP-induced osteoclastogenesis in vitro and PTHrP-induced bone resorption in vivo, suggesting that the p38 MAPK signaling pathway plays a fundamental role in PTHrP-induced osteoclastic bone resorption. PMID:21886782

  1. A novel mature B-cell line (DOBIL-6) producing both parathyroid hormone-related protein and interleukin-6 from a myeloma patient presenting with hypercalcaemia.

    PubMed

    Ohmori, M; Nagai, M; Fujita, M; Dobashi, H; Tasaka, T; Yamaoka, G; Kawanishi, K; Taniwaki, M; Takahara, J

    1998-06-01

    A novel human EBV-negative B-cell line, designated DOBIL-6, was established from a patient with non-secretary myeloma. The DOBIL-6 cell has cytoplasmic gamma protein and expresses CD19, 20, 38, 45RO, VLA-4 and PCA-1 antigens, but lacks CD10, 45RA and VLA5 antigens. Chromosome analysis showed that DOBIL-6 cells had many complex structural abnormalities, including t(11;4) (q13;q32), which were consistent with that of the fresh tumour cells. Interestingly, abundant interleukin-6 (IL-6) and parathyroid hormone-related protein (PTHrP) accumulated in the culture supernatant of DOBIL-6 cells. Hypercalcaemia and splenomegaly associated with plasma cell proliferations which resulted in the expansion of the light zones in the follicles were observed in DOBIL-6 transplanted nude mice. RT-PCR analysis detected mRNA for PTHrP, and IL-6 as well as its receptor (GP80) in DOBIL-6 cells. Treatment of the DOBIL-6 cells with neutralizing anti-IL-6 antibody inhibited their growth in a dose-dependent manner, whereas the addition of exogenous IL-6 stimulated it in serum-depleted conditions. These findings suggest that both IL-6 and PTHrP are produced in DOBIL-6 cells, and that IL-6 promotes its growth by an autocrine mechanism. Since IL-6 is known to stimulate not only the growth of B-cell neoplasms but also osteoclastic bone resorption by cooperating with PTHrP, this simultaneous production of IL-6 and PTHrP might be synergistically linked and play a role in the development of hypercalcaemia of the patient. The DOBIL-6 cell is a useful tool to clarify the mechanism of hypercalcaemia associated with mature B-cell neoplasms. PMID:9674742

  2. Transcriptional regulation of parathyroid hormone-related protein promoter P3 by ETS-1 in adult T-cell leukemia/lymphoma

    PubMed Central

    Richard, V; Nadella, MVP; Green, PL; Lairmore, MD; Feuer, G; Foley, JG; Rosol, TJ

    2009-01-01

    Parathyroid hormone-related protein (PTHrP) plays a primary role in the development of humoral hypercalcemia of malignancy seen in the majority of adult T-cell leukemia/lymphoma (ATLL) patients with human T-cell lymphotropic virus type-1 (HTLV-1) infection. HTLV-1 Tax has been shown to complex with ETS-1 and SP1 to transactivate the PTHrP P3 promoter. Previously, we established a SCID/bg mouse model of human ATL with RV-ATL cells and showed that PTHrP expression was independent of Tax. In this study, we report an inverse correlation of PTHrP with tax/rex mRNA in multiple HTLV-1-positive cell lines and RV-ATL cells. Stimulation of Jurkat T cells with PMA/ionomycin upregulated the PTHrP P3 promoter by a previously characterized Ets binding site and also induced protein/DNA complex formation identical to that observed in RV-ATL cells. Further, we provide evidence that cotransfection with Ets-1 and constitutively active Mek-1 in HTLV-1-negative transformed T cells with stimulation by PMA/ionomycin not only resulted in a robust induction of PTHrP P3 but also formed a complex with ETS-1/P3 EBS similar to that in ATLL cells. Our data demonstrate that transcriptional regulation of PTHrP in ATLL cells can be controlled by T-cell receptor signaling and the ETS and MAPK ERK pathway in a Tax-independent manner. PMID:15889157

  3. Transcriptional regulation of parathyroid hormone-related protein promoter P2 by NF-kappaB in adult T-cell leukemia/lymphoma.

    PubMed

    Nadella, M V P; Dirksen, W P; Nadella, K S; Shu, S; Cheng, A S; Morgenstern, J A; Richard, V; Fernandez, S A; Huang, T H; Guttridge, D; Rosol, T J

    2007-08-01

    Parathyroid hormone-related protein (PTHrP) plays a primary role in the development of humoral hypercalcemia of malignancy (HHM) that occurs in the majority of patients with adult T-cell leukemia/lymphoma (ATLL) due to human T-cell lymphotropic virus type-1 (HTLV-1) infection. We previously showed that ATLL cells constitutively express high levels of PTHrP via activation of promoters P2 and P3, resulting in HHM. In this study, we characterized a nuclear factor-kappaB (NF-kappaB) binding site in the P2 promoter of human PTHrP. Using electrophoretic mobility shift assays, we detected a specific complex in Tax-expressing human T cells composed of p50/c-Rel, and two distinct complexes in ATLL cells consisting of p50/p50 homodimers and a second unidentified protein(s). Chromatin immunoprecipitation assays confirmed in vivo binding of p50 and c-Rel on the PTHrP P2 promoter. Using transient co-transfection with NF-kappaB expression plasmids and PTHrP P2 luciferase reporter-plasmid, we showed that NF-kappaB p50/p50 alone and p50/c-Rel or p50/Bcl-3 cooperatively upregulated the PTHrP P2 promoter. Furthermore, inhibition of NF-kappaB activity by Bay 11-7082 reduced PTHrP P2 promoter-initiated transcripts in HTLV-1-infected T cells. In summary, the data demonstrated that transcriptional regulation of PTHrP in ATLL cells can be controlled by NF-kappaB activation and also suggest a Tax-independent mechanism of activation of PTHrP in ATLL. PMID:17554373

  4. Transcriptional regulation of parathyroid hormone-related protein promoter P3 by ETS-1 in adult T-cell leukemia/lymphoma.

    PubMed

    Richard, V; Nadella, M V P; Green, P L; Lairmore, M D; Feuer, G; Foley, J G; Rosol, T J

    2005-07-01

    Parathyroid hormone-related protein (PTHrP) plays a primary role in the development of humoral hypercalcemia of malignancy seen in the majority of adult T-cell leukemia/lymphoma (ATLL) patients with human T-cell lymphotropic virus type-1 (HTLV-1) infection. HTLV-1 Tax has been shown to complex with ETS-1 and SP1 to transactivate the PTHrP P3 promoter. Previously, we established a SCID/bg mouse model of human ATL with RV-ATL cells and showed that PTHrP expression was independent of Tax. In this study, we report an inverse correlation of PTHrP with tax/rex mRNA in multiple HTLV-1-positive cell lines and RV-ATL cells. Stimulation of Jurkat T cells with PMA/ionomycin upregulated the PTHrP P3 promoter by a previously characterized Ets binding site and also induced protein/DNA complex formation identical to that observed in RV-ATL cells. Further, we provide evidence that cotransfection with Ets-1 and constitutively active Mek-1 in HTLV-1-negative transformed T cells with stimulation by PMA/ionomycin not only resulted in a robust induction of PTHrP P3 but also formed a complex with ETS-1/P3 EBS similar to that in ATLL cells. Our data demonstrate that transcriptional regulation of PTHrP in ATLL cells can be controlled by T-cell receptor signaling and the ETS and MAPK ERK pathway in a Tax-independent manner. PMID:15889157

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

    PubMed

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

    2015-01-01

    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

  6. Parathyroid hormone-related protein-stanniocalcin antagonism in regulation of bicarbonate secretion and calcium precipitation in a marine fish intestine.

    PubMed

    Fuentes, Juan; Power, Deborah M; Canário, Adelino V M

    2010-07-01

    Bicarbonate secretion in the intestine (duodenum) of marine fish has been suggested to play a major role in regulation of calcium availability for uptake. However, while the end process may lead to carbonate precipitation, regulation of transport of calcium and/or bicarbonate may actually result in fine-tuning of calcium availability for transport. To test this hypothesis, sea bream (Sparus auratus) duodenal preparations were mounted in Ussing-type chambers and the effect of parathyroid hormone-related protein (PTHrP) and stanniocalcin 1 (STC 1) on the control of intestinal bicarbonate secretion and calcium transport was analyzed. As expected, PTHrP increased net calcium uptake, as a result of an increase of calcium uptake without changes in calcium efflux. In contrast, purified sea bream STC 1 caused a minor decrease of calcium uptake and a two- to threefold increase in calcium efflux. As a result, STC 1 was able to invert the calcium flux from net calcium uptake to net calcium loss, which is in keeping with its known actions as a hypocalcemic factor. Furthermore, both PTHrP and STC 1 regulate intestinal bicarbonate secretion. PTHrP increased calcium uptake and simultaneously reduced the single factor that induces calcium precipitation, bicarbonate secretion. In contrast, STC 1, while reversing the calcium net flux to make it secretory, promoted intestinal bicarbonate secretion, both actions directed to decrease the calcium gradient across the epithelium and promote immobilization in the form of bicarbonate in the intestinal lumen. Together our results provide robust evidence to support an antagonistic action of PTHrP and STC 1 in the fine control of movements of both calcium and bicarbonate in the intestine of seawater fish. PMID:20410471

  7. Acute changes in serum calcium and parathyroid hormone circulating levels induced by the oral intake of five currently available calcium salts in healthy male volunteers.

    PubMed

    Deroisy, R; Zartarian, M; Meurmans, L; Nelissenne, N; Micheletti, M C; Albert, A; Reginster, J Y

    1997-05-01

    Several calcium supplements are currently available and many of them are marketed without proper comparison of the bioavailability of the actual preparations. The aim of the present trial was to evaluate and compare the acute changes in serum calcium (Ca) and parathyroid hormone (PTH) levels following the oral administration of a vehicle and of five calcium salts currently prescribed in Western Europe. No significant changes in serum Ca or PTH levels were observed after administration of the vehicle. All calcium salts induced significant increases in serum Ca and decreases in serum PTH compared to baseline values. Comparison of the six response curves revealed a significantly greater increase in serum Ca and a greater decrease in serum PTH after each of the calcium salts than observed after the vehicle. However, no statistically significant differences were observed between the different calcium salts for serum Ca increments. The decrease in serum PTH observed after administration of an ossein-hydroxyapatite complex was significantly less important than after the four other calcium salts, even if statistically different than after vehicle. When assessing the area under the curve (AUC) of PTH values, we observed that calcium carbonate and citrate induce a significantly greater decrease in serum PTH than the other calcium salts which are, however, statistically more active than the vehicle. Serum PTH is decreased under the lower limit of the normal range (10 pg/ml), between t60 and t120 for calcium carbonate and citrate and between t60 and t90 for calcium gluconolactate while the mean PTH values remain within the normal range throughout the study with calcium pidolate, the ossein-hydroxyapatite complex and the vehicle. In conclusion, all calcium preparations significantly increase serum calcium and decrease serum parathormone, compared to what is observed after oral intake of a vehicle. However, significant differences in suppression of parathormone are observed between the different calcium preparations and might be of importance for their clinical use. PMID:9184261

  8. Loss of cancellous bone mass and connectivity in ovariectomized rats can be restored by combined treatment with parathyroid hormone and estradiol.

    PubMed Central

    Shen, V; Dempster, D W; Birchman, R; Xu, R; Lindsay, R

    1993-01-01

    To evaluate the potential use of a combination of antiresorption and bone formation-promoting agents as a treatment for postmenopausal osteoporosis, we examined the effects of combined and separate administration of estrogen (17 beta-estradiol, 30 micrograms/kg per d, s.c.) and parathyroid hormone (rPTH [1-34], 40 micrograms/kg per d, s.c.) on the proximal tibia of ovariectomized (Ovx) rats. The treatments lasted for 4 wk and were initiated 1, 3, and 5 wk after surgery. Ovx resulted in rapid loss of cancellous bone volume (Cn-BV/TV) as well as trabecular connectivity, as determined by two dimensional strut analysis. When administered in a preventive mode, treatment beginning 1 wk post-Ovx, estrogen or PTH treatment alone preserved Cn-BV/TV and trabecular connectivity, and combined estrogen and PTH treatment caused a 40% increment in Cn-BV/TV while maintaining comparable trabecular connectivity with that seen in the Sham-operated animals. When administered in a curative mode to rats with established osteoporosis, treatments beginning 3 or 5 wk post-Ovx, estrogen or PTH treatment alone prevented further loss of connectivity and Cn-BV/TV, whereas the combined treatment resulted in as much as a 300% improvement in one of the parameters of trabecular connectivity, node to node strut length, and a 106% increase in Cn-BV/TV, with respect to the bone status at the initiation of treatment. The beneficial effects of this combined treatment derive from estrogen's ability to prevent accelerated bone resorption and, simultaneously, PTH's promotion of bone formation. These data demonstrate, in an animal model, that therapies can be devised to cure the skeletal defects associated with established osteoporosis. PMID:8514860

  9. Use of Calcium, Folate, and Vitamin D3–Fortified Milk for 6 Months Improves Nutritional Status But Not Bone Mass or Turnover, in a Group of Australian Aged Care Residents

    Microsoft Academic Search

    Jessica A. Grieger; Caryl A. Nowson

    2009-01-01

    In residential care, inadequate calcium and folate intakes and low serum vitamin D (25(OH)D) concentrations are common. We assessed whether daily provision of calcium, folate, and vitamin D3–fortified milk for 6 months improved nutritional status (serum micronutrients), bone quality (heel ultrasound), bone turnover markers (parathyroid hormone, C-terminal collagen I telopeptide, terminal propeptide of type I procollagen), and\\/or muscle strength and

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

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

    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.

  11. Intermittent parathyroid hormone (PTH) treatment and age-dependent effects on rat cancellous bone and mineral metabolism.

    PubMed

    Friedl, Gerald; Turner, Russell T; Evans, Glenda L; Dobnig, Harald

    2007-11-01

    In recent years, intermittent PTH treatment has been investigated extensively for its efficacy in preventing osteoporotic fractures and to improve fracture healing and implant fixation. Although these tasks concern patients of all ages, very little is known about whether aging impacts the bone anabolic response to PTH. Female Sprague-Dawley rats of 1, 3, and 13 months of age were either treated by hPTH-(1-34) or by vehicle solution (CTR) for 1 week. As main outcome measures, we determined the effects on static and dynamic histomorphometry of cancellous bone. In addition, we measured gene expression in femur and serum parameters reflecting bone turnover and mineral metabolism. There was a profound decrease in bone formation rate (BFR) with aging in CTR rats, whereas PTH treatment resulted in a significant relative 1.5-, 3-, and 4.7-fold increase in BFR, without altering indices of bone resorption. Aging decreased and PTH increased mRNA levels for bone matrix proteins and growth factors in a gene-specific manner. In younger animals, PTH-induced a marked stimulation in the mineral apposition rate with no effect on osteoblast number, whereas the latter was increased in older animals (1.0-, 1.7-, and 3.1-fold). Treatment with PTH in young rats led to a significant increase in trabecular number (1.6-2.6/mm, p < 0.05), whereas older rats demonstrated increases in trabecular thickness only (52.8-77.8 microm, p < 0.001). Although PTH increased bone formation at all ages, we found significant age-related differences in the cellular and molecular mechanisms involved in the bone anabolic response to the hormone. PMID:17557320

  12. Vitamin D supplementation in obese type 2 diabetes subjects in Ajman, UAE: a randomized controlled double-blinded clinical trial

    PubMed Central

    Sadiya, A; Ahmed, S M; Carlsson, M; Tesfa, Y; George, M; Ali, S H; Siddieg, H H; Abusnana, S

    2015-01-01

    Objectives: To study the effect of Vitamin D3 supplementation on metabolic control in an obese type 2 diabetes Emirati population. Methods: This randomized double-blind clinical trial was conducted with 87 vitamin D-deficient obese, type 2 diabetic participants. The vitamin D-group (n=45) and the placebo group (n=42) were matched for gender, age, HbA1c and 25-hydroxy vitamin D (25(OH) D) at the baseline. The study was divided into two phases of 3 months each; in phase 1, the vitamin D-group received 6000?IU vitamin D3/day followed by 3000?IU vitamin D3/day in phase 2, whereas the placebo group (n=42) received matching placebo. Results: After supplementation, serum 25(OH) D peaked in the vitamin D-group in phase 1 (77.2±30.1?nmol/l, P=0.003) followed by a decrease in the phase 2 (61.4±18.8?nmol/l, P=0.006), although this was higher compared with baseline. In the placebo group, no difference was observed in the serum 25(OH) D levels throughout the intervention. Relative to baseline serum, parathyroid hormone decreased 24% (P=0.003) in the vitamin D-group in phase 2, but remained unchanged in the placebo group. No significant changes were observed in blood pressure, fasting blood glucose, HbA1c, C-peptide, creatinine, phosphorous, alkaline phosphatase, lipids, C-reactive protein or thyroid stimulating hormone concentrations compared with baseline in either group. Conclusions: Six months of vitamin D3 supplementation to vitamin D-deficient obese type 2 diabetes patients in the UAE normalized the vitamin D status and reduced the incidence of eucalcemic parathyroid hormone elevation but showed no effect on the metabolic control. PMID:25406966

  13. Functioning Oxyphil Parathyroid Adenoma: A Case Report

    PubMed Central

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

    2014-01-01

    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

  14. New Clinical Trials with Vitamin D and Analogs in Renal Disease

    PubMed Central

    Kumar, Rajiv

    2015-01-01

    Two new clinical trials highlight refinements in the use of vitamin D and its analogs in the treatment of secondary hyperparathyroidism in ESRD, and the treatment of proteinuria in diabetics. In patients with ESRD, alphacalcidol is as effective as paricalcitol in suppressing parathyroid hormone; the occurrence of hypercalcemia and hyperphosphatemia is infrequent and similar with the two analogs1. Oral cholecalciferol reduces albuminuria and urinary TGF-?1 in patients with type 2 diabetes mellitus and proteinuria2. PMID:21832981

  15. Relationship Between Disease Activity and Serum Levels of Vitamin D Metabolites and PTH in Rheumatoid Arthritis

    Microsoft Academic Search

    P. Oelzner; A. Müller; F. Deschner; M. Hüller; K. Abendroth; G. Hein; G. Stein

    1998-01-01

    .   In several studies on patients with rheumatoid arthritis, an association of bone loss with a persistently high disease activity\\u000a has been found. The aim of our study was to investigate the relation between disease activity and serum levels of vitamin\\u000a D metabolites, parathyroid hormone (PTH), and parameters of bone turnover in patients with rheumatoid arthritis. A total of\\u000a 96

  16. Vitamins

    MedlinePLUS

    ... wheat and oats wheat germ leafy green vegetables vegetable oils like sunflower, canola, and olive egg yolks nuts ... foods are rich in vitamin K? leafy green vegetables dairy products, like milk and yogurt broccoli soybean oil When your body gets this vitamin and the ...

  17. The effects of 1,25-dihydroxycholecalciferol, parathyroid hormone, and thyroxine on trabecular bone remodeling in adult dogs. A histomorphometric study.

    PubMed

    High, W B; Capen, C C; Black, H E

    1981-12-01

    The effects of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3), parathyroid hormone (PTH), and L-thyroxine (T4) on trabecular bone remodeling were evaluated by histomorphometric methods in adult female beagle dogs. Intravenous 1,25-(OH)2D3 (1.25 micrograms/day in equally divided doses) was administered intermittently for 6 days and withdrawn 14 days for three complete cycles. PTH was administered intravenously (2.5 U/kg/day) in divided doses 6 hours apart for 60 days. Thyroxine was given orally (1.0 mg/kg/day) in divided doses for a similar interval. Static and dynamic changes were evaluated using tetracycline and DCAF (2,4 BIS) N, N', Di (carboxymethyl) (amino methyl fluorescein) in vivo double labeling of bone from the iliac crest taken before treatment and after 60 days. The intermittent administration of 1,25-(OH)2D3 stimulated the bone resorption rate and depressed the formation rate. 1,25-(OH)2D3 increased trabecular resorption surfaces; osteoid surface, volume, and thickness; mineralization lag time; and osteoblast number but decreased the bone volume. Multiple small daily doses of PTH resulted in an overall negative balance in trabecular bone. This was associated with an increased trabecular surface-to-volume ratio, bone resorption and formation rates, active forming surfaces, osteoid volume and surface, life span of bone forming and resorbing sites, and the number of osteoclast nuclei. Thyroxine appeared to increase bone mass by enhancing the switch-over from the resorptive to the formative phase of remodeling. Coupling between osteoid apposition and mineralization was increased by recruiting more forming sites and prolonging their life span. Thyroxine increased bone resorption and formation rates, trabecular bone volume and balance, number of osteoclast nuclei, and life span of bone forming sites. The osteoid seam thickness and mineralization lag time were decreased. The present study demonstrated that 1,25-(OH)2D3, PTH, and thyroxine at the dose and schedule used, markedly altered stimulators of remodeling in trabecular bone of adult dogs. PMID:6895577

  18. Ets2 and protein kinase C epsilon are important regulators of parathyroid hormone-related protein expression in MCF-7 breast cancer cells.

    PubMed

    Lindemann, Ralph K; Braig, Melanie; Hauser, Craig A; Nordheim, Alfred; Dittmer, Jürgen

    2003-06-15

    Parathyroid hormone-related protein (PTHrP) promotes the metastatic potential and proliferation of breast cancer cells, and acts anti-apoptotically. In invasive MDA-MB-231 breast cancer cells, transforming growth factor beta-regulated PTHrP synthesis is mediated by an Ets1/Smad3-dependent activation of the PTHrP P3 promoter. In the present study, we studied the regulation of PTHrP expression in non-invasive, Ets1-deficient and transforming growth factor beta-resistant MCF-7 cells. We found PMA to be a strong stimulator of P3-dependent PTHrP expression in MCF-7 cells. Mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK) kinase 1 (MEK-1)/ERK1/2 inhibitor PD98059 interfered with this activity. Promoter studies revealed that the PMA effect depended on the Ets and stimulating protein-1 (Sp1)-binding sites. Of several Ets factors tested, Ets2, but not Ese-1, Elf-1 or Ets1, supported the PMA-dependent increase in promoter activity. PD98059 and a threonine to alanine mutation of the ERK1/2-responsive Ets2 phosphorylation site at position 72 inhibited the Ets2/PMA effect. Activated protein kinase C (PKC) epsilon could mimic PMA by stimulating the P3 promoter alone or in co-operation with Ets2 in an MEK-1/ERK1/2-dependent manner. Activated PKC alpha, although capable of co-operating with Ets2, failed to induce transcription from the P3 promoter on its own. The Ets2/PKalpha synergistic effect was neither sensitive to PD98059 nor to Thr(72)/Ala(72) mutation. PMA neither increased the expression of Sp1 nor modulated the transcriptional activity of Sp1. However, it induced the displacement of a yet unknown factor from the Sp1-binding site, which may result in Sp1 recruitment to the promoter. Our results suggest an ERK1/2-dependent Ets2/PKC epsilon synergism to be involved in PTHrP expression in MCF-7 breast cancer cells. PMID:12628005

  19. Expression of parathyroid hormone-related protein during immortalization of human peripheral blood mononuclear cells by HTLV-1: Implications for transformation

    PubMed Central

    Nadella, Murali VP; Shu, Sherry T; Dirksen, Wessel P; Thudi, Nanda K; Nadella, Kiran S; Fernandez, Soledad A; Lairmore, Michael D; Green, Patrick L; Rosol, Thomas J

    2008-01-01

    Background Adult T-cell leukemia/lymphoma (ATLL) is initiated by infection with human T-lymphotropic virus type-1 (HTLV-1); however, additional host factors are also required for T-cell transformation and development of ATLL. The HTLV-1 Tax protein plays an important role in the transformation of T-cells although the exact mechanisms remain unclear. Parathyroid hormone-related protein (PTHrP) plays an important role in the pathogenesis of humoral hypercalcemia of malignancy (HHM) that occurs in the majority of ATLL patients. However, PTHrP is also up-regulated in HTLV-1-carriers and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients without hypercalcemia, indicating that PTHrP is expressed before transformation of T-cells. The expression of PTHrP and the PTH/PTHrP receptor during immortalization or transformation of lymphocytes by HTLV-1 has not been investigated. Results We report that PTHrP was up-regulated during immortalization of lymphocytes from peripheral blood mononuclear cells by HTLV-1 infection in long-term co-culture assays. There was preferential utilization of the PTHrP-P2 promoter in the immortalized cells compared to the HTLV-1-transformed MT-2 cells. PTHrP expression did not correlate temporally with expression of HTLV-1 tax. HTLV-1 infection up-regulated the PTHrP receptor (PTH1R) in lymphocytes indicating a potential autocrine role for PTHrP. Furthermore, co-transfection of HTLV-1 expression plasmids and PTHrP P2/P3-promoter luciferase reporter plasmids demonstrated that HTLV-1 up-regulated PTHrP expression only mildly, indicating that other cellular factors and/or events are required for the very high PTHrP expression observed in ATLL cells. We also report that macrophage inflammatory protein-1? (MIP-1?), a cellular gene known to play an important role in the pathogenesis of HHM in ATLL patients, was highly expressed during early HTLV-1 infection indicating that, unlike PTHrP, its expression was enhanced due to activation of lymphocytes by HTLV-1 infection. Conclusion These data demonstrate that PTHrP and its receptor are up-regulated specifically during immortalization of T-lymphocytes by HTLV-1 infection and may facilitate the transformation process. PMID:18541021

  20. Vitamins

    MedlinePLUS

    ... fortified cereals, egg yolk, beef liver, fish, milk, vegetable oils, nuts, fruits, peas, beans, broccoli, and spinach. H ( ... cheese, spinach, broccoli, brussels sprouts, kale, cabbage, tomatoes, plant oils. Your body usually makes all the vitamin K ...

  1. Vitamin D control of osteoblast function and bone extracellular matrix mineralization.

    PubMed

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

    2001-01-01

    Vitamin D is the major regulator of calcium homeostasis and protects the organism from calcium deficiency via effects on the intestine, kidney, parathyroid gland, and bone. Disturbances in the vitamin D endocrine system (e.g., vitamin D-dependent rickets type I and type II), result in profound effects on the mineralization of bone. Recent studies with vitamin D receptor knockout mice also show effects on bone. It is questioned whether vitamin D has a direct effect on bone formation and mineralization. In rickets and particular vitamin D receptor knockout mice, calcium supplementation restores bone mineralization. However, the vitamin D receptor is present in osteoblasts, and vitamin D affects the expression of various genes in osteoblasts. This review focuses on the role of vitamin D in the control of osteoblast function and discusses the current knowledge of the direct effects of vitamin D on mineralization. Moreover, the role of vitamin D metabolism and the mechanism of action of vitamin D and interaction with other hormones and factors are discussed. PMID:11693961

  2. Distinct association of gene polymorphisms of estrogen receptor and vitamin D receptor with lumbar spondylosis in post-menopausal women

    Microsoft Academic Search

    Yu Koshizuka; Naoshi Ogata; Masataka Shiraki; Takayuki Hosoi; Atsushi Seichi; Katsushi Takeshita; Kozo Nakamura; Hiroshi Kawaguchi

    2006-01-01

    Contribution of genetic backgrounds to the etiology of lumbar spondylosis has been suggested by epidemiological studies. This study was designed to determine the association of restriction fragment length polymorphisms (RFLPs) of estrogen receptor (ER), vitamin D receptor (VDR), parathyroid hormone (PTH) and interleukin-1? (IL-1?) genes with the radiological severity of lumbar spondylosis at the disk level from L1\\/2 to L5\\/S1

  3. Postural shortening due to primary hyperparathyroidism caused by parathyroid adenoma.

    PubMed

    Imelda, Fitri; Bandar, Ivo Novita Sah; Setiyohadi, Bambang; Suwondo, Pradana; Nasar, I Made

    2006-01-01

    Osteoporosis can be primary or secondary. Secondary osteoporosis is the result of an underlying disease such as an endocrine abnormality, and an example of such is primary hyperparathyroidism. The most common cause of primary hyperparathyroidism is parathyroid gland adenoma. The diagnosis of primary hyperparathyroidism is based on the following biochemical examinations: parathyroid hormone, serum calcium, creatinine clearance, 24 hour urinary calcium, and another examination such as parathyroid gland scan. This is a rare case of an adult man who presented with a chief complaint of decreasing body height, back pain, difficulty in taking deep breaths and difficulty in his activities. The patient was diagnosed with primary hyperparathyroidism caused by parathyroid gland adenoma. His complaint was reduced after parathyroidectomy. His new complaint was that his tooth can be pulled out easily. We found high levels of parathyroid hormone and low levels of serum calcium caused by secondary hyperparathyroidism. PMID:16799210

  4. Single-sperm typing: Determination of genetic distance between the sup G. gamma. -globulin and parathyroid hormone loci by using the polymerase chain reaction and allele-specific oligomers

    SciTech Connect

    Cui, Xiangfeng; Li, Honghua; Galas, D.; Arnheim, N. (Univ. of Southern California, Los Angeles (USA)); Goradia, T.M. (Univ. of California School of Medicine, Los Angeles (USA) Harvard Univ., Cambridge, MA (USA)); Lange, K. (Univ. of California School of Medicine, Los Angeles (USA)); Kazazian, H.H. Jr. (Johns Hopkins Univ., Baltimore, MD (USA))

    1989-12-01

    The frequency of recombination between the {sup G}{gamma}-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. The maximum likelihood recombination fraction estimate of 0.16 falls well within previous estimates based on family studies. With current technology and a sample size of 1000 sperm, recombination fractions down to {approx}0.009 can be estimated with statistical reliability; with a sample size of 5000 sperm, this value drops to about 0.004. Reasonable technological improvements could result in the detection of recombination frequencies <0.001.

  5. Vitamin D--deficient rickets in a child with cow's milk allergy.

    PubMed

    Barreto-Chang, Odmara L; Barreto-Chang, Odmara; Pearson, Doriel; Shepard, W Elizabeth; Longhurst, Christopher A; Longhurst, Chris; Greene, Alan

    2010-08-01

    This article describes the case of a 16-month-old Hispanic male toddler with cow's milk allergy living in northern California who was admitted to a children's hospital for weight loss and markedly elevated levels of serum alkaline phosphatase and parathyroid hormone. At a routine outpatient well-child visit, his mother expressed concern about a decrease in his appetite and activity level. A detailed diet history revealed that breast milk was his primary source of nutrition during his first year of life and he had not been given supplemental vitamins. With attempts to introduce cow's milk formula, he had developed a rash and swelling around the mouth. Shortly after his first birthday, his mother weaned him from breast milk and introduced unfortified rice milk as a palatable milk substitute. Upon admission he was pale and lethargic; his laboratory studies were remarkable for elevated serum alkaline phosphatase and parathyroid hormone and low levels of phosphorus, 25-hydroxy-vitamin D, and ferritin. Lower extremity radiographic studies were consistent with rickets. After 5 weeks of therapy with vitamin D(3) and iron, his serum 25-hydroxy-vitamin D level normalized. Within 12 weeks following therapy, the child demonstrated significant clinical improvement, with resolution of growth failure and bone reossification. His activity level had returned to normal. This case emphasizes the importance of adequate vitamin D intake for children with special attention to those who might have nutrition deficiencies attributable to milk allergy. PMID:20702845

  6. Vitamin D status in diabetic Egyptian children and adolescents: a case–control study

    PubMed Central

    2013-01-01

    Background Recently, studies suggesting that vitamin D deficiency correlates with the severity and frequency of Type 1 (insulin-dependent) diabetes mellitus (T1DM) and that vitamin D supplementation reduces the risk of developing T1DM have been reported. Objective In this study, we aimed to assess vitamin D status in Egyptian children and adolescents with T1DM. Methods This was a case–control study including 80 T1DM diagnosed cases aged 6 to 16 years and 40 healthy children with comparable age and gender as the control group. For all subjects, serum 25 (OH) D levels were measured by ELISA, Serum parathyroid hormone (PTH) and serum insulin were measured by an electrochemiluminesce immunoassay. Serum glucose, Glycosylated hemoglobin (HbA1c) levels and homeostasis model assessment of insulin resistance (HOMA-IR) were also assessed. Results Compared to the control group, serum vitamin D levels were not significantly lower in diabetic subjects (24.7?±?5.6 vs 26.5?±?4.8 ng/ml; P?>?0.05). Among diabetic cases 44(55%) were vitamin D deficient; meanwhile 36(45%) cases had normal vitamin D level (P?parathyroid hormone level; meanwhile, none of the control group had 2ry hyperparathyroidism (P?vitamin D deficient diabetic cases and those with normal vitamin D level as regards HOMA-IR and diabetes duration (P?vitamin D status; especially in diabetic children and adolescents, should be disseminated to the public. PMID:24228797

  7. Supplementation of dietary vitamins, protein and probiotics on semen traits and immunohistochemical study of pituitary hormones in zinc-induced molted broiler breeders.

    PubMed

    Khan, Rifat Ullah; Rahman, Zia-ur-; Javed, Ijaz; Muhammad, Faqir

    2013-09-01

    The purpose of this study was to investigate the effect of dietary vitamin E and vitamin C, probiotics mixture and protein level and their combination on semen quality and immunohistochemical study of some pituitary hormones in male broiler breeders. One hundred and eighty male broiler breeders 65 weeks old were divided into six groups by completely randomized design. The birds were subjected to zinc-induced molt by mixing zinc oxide at the rate of 3000mg/kg in the feed. After molting, one group was fed control diet (CP16%). The other groups were fed vitamin E (100IU/kg), vitamin C (500IU/kg), probiotics (50mg/L of drinking water), protein (CP14%) and combination of these components. These treatments were given for five weeks. After the feeding period, semen samples were taken and analyzed for semen volume, sperm concentration, motility and dead sperm percentage. Pituitary samples were collected from three birds per replicate and were processed for immunohistochemical study. The results of semen quality parameters revealed that semen volume and sperm motility were significantly high in the vitamin E fed group, while the dead sperm percentage decreased significantly in the vitamin C group. The morphometric analysis revealed that compared to other groups, vitamin E caused a significant increase in the size and area of FSH, LH gonadotropes and lactotropes. These results showed that vitamin E alone may play some role in the enhancement of semen quality and growth of gonadotropes and lactotropes. PMID:23522908

  8. Green fluorescent protein fused to peptide agonists of two dissimilar G protein-coupled receptors: novel ligands of the bradykinin B2 (rhodopsin family) receptor and parathyroid hormone PTH1 (secretin family) receptor

    PubMed Central

    Charest-Morin, Xavier; Fortin, Jean-Philippe; Bawolak, Marie-Thérčse; Lodge, Robert; Marceau, François

    2013-01-01

    We hypothesized that peptide hormone sequences that stimulate and internalize G protein-coupled receptors (GPCRs) could be prolonged with a functional protein cargo. To verify this, we have selected two widely different pairs of peptide hormones and GPCRs that nevertheless share agonist-induced arrestin-mediated internalization. For the parathyroid hormone (PTH) PTH1 receptor (PTH1R) and the bradykinin (BK) B2 receptor (B2R), we have designed fusion proteins of the agonists PTH1-34 and maximakinin (MK, a BK homologue) with the enhanced green fluorescent protein (EGFP), thus producing candidate high molecular weight ligands. According to docking models of each hormone to its receptor, EGFP was fused either at the N-terminus (MK) or C-terminus (PTH1-34) of the ligand; the last construction is also secretable due to inclusion of the preproinsulin signal peptide and has been produced as a conditioned medium. EGFP-MK has been produced as a lysate of transfected cells. Using an enzyme-linked immunosorbent assay (ELISA) for GFP, average concentrations of 1.5 and 1670 nmol/L, respectively, of ligand were found in these preparations. The functional properties and potential of these analogs for imaging receptor-expressing cells were examined. Microscopic and cytofluorometric evidence of specific binding and internalization of both fusion proteins was obtained using recipient HEK 293a cells that expressed the cognate recombinant receptor. Endosomal colocalization studies were conducted (Rab5, Rab7, ?-arrestin1). Evidence of agonist signaling was obtained (expression of c-Fos, cyclic AMP responsive element (CRE) reporter gene for PTH1-34-EGFP). The constructs PTH1-34-EGFP and EGFP-MK represent bona fide agonists that support the feasibility of transporting protein cargoes inside cells using GPCRs. PMID:25505558

  9. Clinical Significance of Female-hormones and Cytokines in Breast Cancer Patients Complicated with Aromatase Inhibitor-related Osteoarthropathy - Efficacy of Vitamin E

    PubMed Central

    Kiyomi, Anna; Makita, Masujiro; Iwase, Takuji; Tanaka, Sachiko; Onda, Kenji; Sugiyama, Kentaro; Takeuchi, Hironori; Hirano, Toshihiko

    2015-01-01

    Introduction: Aromatase inhibitor use for postmenopausal hormone-sensitive breast cancer patients often results in drug-induced osteoarthropathy, while its accurate mechanism has not been clarified. We investigated the implication of female hormones and several cytokines in osteoarthropathy complicated with aromatase inhibitor treatment, and the efficacy of vitamin E on the severity of osteoarthropathy, in breast cancer patients. Methods: Sixty two breast cancer patients treated with aromatase inhibitor for average of 1.77 years were included. These patients were orally administered vitamin E (150mg/day) for 29.8 days to alleviate aromatase inhibitor-related osteoarthropathy. Severity of osteoarthropathy was scored, and the patients were grouped based on the severity or vitamin E efficacy. Serum estradiol, progesterone, vitamin E, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), IL-2, IL-4, IL-6, IL-10, and IL-17A concentrations were measured by ELISA or beads array procedures followed by flow cytometry. Results: There was no significant difference in serum concentrations of the biomarkers between the severe and the mild osteoarthropathy groups before vitamin E administration. The osteoarthropathy scores significantly decreased after vitamin E administration (p=0.0243), while serum-estradiol concentrations did not change. The serum-estradiol concentrations before vitamin E administration in the group sensitive to the vitamin E efficacy were significantly lower, as compared with those in the insensitive group (p=0.0005). The rate of the highly sensitive patients to the vitamin E efficacy in those exhibiting low serum-estradiol concentrations was significantly higher than that in the high serum-estradiol group (p=0.0004). In the sensitive group, serum-estradiol concentrations after taking vitamin E were significantly higher than those before taking vitamin E (p=0.0124). Conclusions: Vitamin E administration seemed to be a potential way for relieving osteoarthropathy complicated with aromatase inhibitor use. Using serum-estradiol concentration, it would be possible to select out the breast cancer patients who will respond well to the vitamin E therapy for osteoarthropathy complicated with aromatase inhibitor. PMID:25767607

  10. Vitamin D-deficient osteomalacia due to excessive self-restrictions for atopic dermatitis.

    PubMed

    Shikino, Kiyoshi; Ikusaka, Masatomi; Yamashita, Tomoko

    2014-01-01

    A 34-year-old Japanese woman presented with a 2-year history of generalised bone pain, muscle weakness and gait disturbance. The patient had been following a restricted diet (without fish or dairy products) and avoiding ultraviolet exposure for 8?years to manage her worsening atopic dermatitis. Physical examination revealed generalised bone tenderness and bilateral symmetric proximal muscle weakness. Vitamin D-deficient osteomalacia was diagnosed based on the laboratory examination findings, which indicated high serum alkaline phosphatase, high intact parathyroid hormone, and low 25-hydroxyvitamin D levels. Her symptoms improved after oral active vitamin D and calcium administration. To the best our knowledge, this case is the first report of vitamin D-deficient osteomalacia in an adult patient due to excessive dietary restriction for managing atopic dermatitis. We emphasise the importance of increasing awareness of vitamin D deficiency as a risk factor for the development of osteomalacia, and caution against excessive avoidance of sun exposure and dietary restriction. PMID:25100811

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

    PubMed Central

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

    2010-01-01

    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

  12. Iodine metabolism and thyroid-related functions in organisms lacking thyroid follicles: are thyroid hormones also vitamins?

    PubMed

    Eales, J G

    1997-04-01

    Thyroid-related functions in organisms devoid of follicular thyroid tissue have been reviewed. In the lamprey, a primitive vertebrate, the larva concentrates iodide and synthesizes thyroid hormones (TH) by iodoperoxidase (IP)-mediated iodination of a thyroglobulin (TG)-like molecule in a subpharyngeal afollicular endostyle. The endostyle is the thyroid homolog, and it reorganizes into a follicular thyroid at metamorphosis to the adult. Ascidians and amphloxus, invertebrate protochordate relatives of vertebrates, also concentrate iodide and synthesize TH in a subpharyngeal afollicular endostyle, but the endostyle never transforms to follicles. Ascidian plasma contains L-thyroxine and its more biologically active derivative 3,5,3'-triiodo-L-thyronine, and TH receptors exist, but TH effects are poorly understood. No other invertebrates possess an endostyle. Several invertebrates concentrate iodide at other sites and form protein-incorporated iodohistidines and iodotyrosines; however, de novo iodothyronine biosynthesis through IP-mediated TG iodination has not been established. Nevertheless, TH occur in invertebrates, and exogenous iodothyrosines or iodothyronines have effects on jellyfish, insects, and sea urchins. Furthermore, gut bacteria metabolize TH, and plants may synthesize TH by nonenzymatic oxidative iodination. Thus, TH occur in many organisms and, after ingestion and enteric absorption, can enter the food chain. Indeed, sea urchin larvae obtain TH required to induce metamorphosis from plant diatoms. Thyroid hormones can therefore have vitamin-like effects and, in conjunction with vitamin D, and possibly with other steroids, may be more aptly termed vitamones. Availability of exogenous TH has implications for models of invertebrate and vertebrate TH metabolism and iodine salvaging, and it may explain the prominent and probable ancestral role of peripheral mechanisms in regulating thyroidal status. PMID:9111521

  13. DNA complementary to parathyroid mRNA directs synthesis of pre-proparathyroid hormone in a linked transcription-translation system

    Microsoft Academic Search

    Henry M. Kronenberg; Bryan E. Roberts; Joel F. Habener; John T. Potts; Alexander Rich

    1977-01-01

    DNA complementary in sequence to the messenger RNA for pre-proparathyroid hormone was synthesised using reverse transcriptase. In a linked transcription-translation system using RNA polymerase and cell-free extract from wheat germ, the DNA directed the synthesis of a protein identified as pre-proparathyroid hormone by N-terminal Sequencing and by electrophoretic and immunologic criteria.

  14. The Role of Vitamin D in Autoimmune Hepatitis

    PubMed Central

    Luong, Khanh vinh quoc; Nguyen, Lan Thi Hoang

    2013-01-01

    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

  15. Vitamin D Deficiency is Prevalent in Females with Rett Syndrome

    PubMed Central

    Motil, Kathleen J.; Barrish, Judy O.; Lane, Jane; Geerts, Suzanne P.; Annese, Fran; McNair, Lauren; Percy, Alan K.; Skinner, Steven A; Neul, Jeffrey L.; Glaze, Daniel G.

    2013-01-01

    Objectives To determine the prevalence of vitamin D deficiency and identify the relation between 25-hydroxyvitamin D [25(OH)D] levels and the consumption of dietary sources of vitamin D or exposure to anticonvulsants in females with Rett syndrome (RTT). Study design Retrospective review of the medical records of 284 females with RTT to determine serum 25(OH)D and parathyroid hormone levels, nutritional status, dietary sources of vitamin D, exposure to anticonvulsants, degree of mobility, and MECP2 status. Results Twenty percent of females who were tested (n=157) had 25(OH)D levels <50 nmol/L. Multivitamin supplements, vitamin D fortified milk, and commercial formulas were consumed by 40%, 52%, and 54%. Anticonvulsants were used by 57% and 39% ambulated independently. Median 25(OH)D levels were lower in individuals who did not receive multivitamin supplements (p<0.05) or commercial formulas (p<0.001) than in those who did. Median 25(OH)D levels differed (p<0.01) among racial and ethnic groups, but the number in some groups was small. Nutritional status, use of anticonvulsants, degree of mobility, and MECP2 status did not influence 25(OH)D levels. Conclusion Vitamin D deficiency is prevalent in females with RTT. The use of multivitamin supplements or commercial formulas is associated with improved vitamin D levels. Attention to vitamin D may enhance bone mineral deposition and reduce the frequency of bone fractures in these individuals. PMID:21637127

  16. Regulation of calcitriol biosynthesis and activity: focus on gestational vitamin D deficiency and adverse pregnancy outcomes.

    PubMed

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

    2015-01-01

    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

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

    PubMed Central

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

    2015-01-01

    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

  18. Reduction of the vitamin D hormonal system in kidney disease is associated with increased renal inflammation

    Microsoft Academic Search

    Daniel Zehnder; Marcus Quinkler; Kevin S Eardley; Rosemary Bland; Julia Lepenies; Susan V Hughes; Neil T Raymond; Alexander J Howie; Paul Cockwell; Paul M Stewart; Martin Hewison

    2008-01-01

    To examine any potential role for 1,25-dihydroxyvitamin D (1,25(OH)2D) in inflammation associated with chronic kidney disease we measured vitamin D metabolites, markers of inflammation and gene expression in 174 patients with a variety of kidney diseases. Urinary MCP-1 protein and renal macrophage infiltration were each significantly but inversely correlated with serum 1,25(OH)2D levels. Logistic regression analysis with urinary MCP-1 as

  19. Prevalence and Prognostic Implications of Vitamin D Deficiency in Chronic Kidney Disease

    PubMed Central

    Obi, Yoshitsugu; Hamano, Takayuki; Isaka, Yoshitaka

    2015-01-01

    Vitamin D is an important nutrient involved in bone mineral metabolism, and vitamin D status is reflected by serum total 25-hydroxyvitamin D (25[OH]D) concentrations. Vitamin D deficiency is highly prevalent in patients with chronic kidney disease (CKD), and nutritional vitamin D supplementation decreases elevated parathyroid hormone concentrations in subgroups of these patients. Furthermore, vitamin D is supposed to have pleiotropic effects on various diseases such as cardiovascular diseases, malignancies, infectious diseases, diabetes, and autoimmune diseases. Indeed, there is cumulative evidence showing the associations of low vitamin D with the development and progression of CKD, cardiovascular complication, and high mortality. Recently, genetic polymorphisms in vitamin D-binding protein have received great attention because they largely affect bioavailable 25(OH)D concentrations. This finding suggests that the serum total 25(OH)D concentrations would not be comparable among different gene polymorphisms and thus may be inappropriate as an index of vitamin D status. This finding may refute the conventional definition of vitamin D status based solely on serum total 25(OH)D concentrations. PMID:25883412

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

    Microsoft Academic Search

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

    1993-01-01

    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

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

    E-print Network

    Kalueff, Allan V.

    ]. 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]. Calcitriol is the main biologically active form of vita min D3. Together with calcidiol, vitamin D3

  2. Parathyroid autotransplantation during thyroidectomy. Results of long-term follow-up.

    PubMed Central

    Olson, J A; DeBenedetti, M K; Baumann, D S; Wells, S A

    1996-01-01

    SUMMARY BACKGROUND DATA: Permanent hypoparathyroidism is a recognized complication of thyroidectomy. Operative strategies to prevent this complication include preservation of parathyroid glands in situ and autotransplantation of parathyroid glands resected or devascularized during thyroidectomy. METHODS: An analysis of 194 patients having thyroidectomy and simultaneous parathyroid autotransplantation at Barnes Hospital from 1990 to 1994 was performed. Data were collected regarding patient demographics, indication for thyroidectomy, operative procedure, pathologic diagnoses, and postoperative course, including biochemical assessment of parathyroid autograft function. RESULTS: Of 194 patients having either total, subtotal, or completion thyroidectomy, 104 (54%) experienced a [Ca(+2)]nadir less than or equal to 8.0 mg/dL and had symptoms and signs of hypocalcemia. Parathyroid autotransplantation was successful in 103 (99%) of these 104 cases and resulted in a 1.0% incidence of hypoparathyroidism in this series. CONCLUSIONS: Although preservation of parathyroid glands in situ is desirable, routine parathyroid autotransplantation during thyroidectomy virtually eliminates postoperative hypoparathyroidism. Normal parathyroid glands resected or devascularized during thyroidectomy for well-differentiated thyroid carcinoma or benign disease should be transplanted in the sternocleidomastoid muscle. Patients with Multiple Endocrine Neoplasia type 2A should have parathyroid glands resected at the time of thyroidectomy for medullary thyroid carcinoma and transplanted in the nondominant forearm. Postoperative management in most patients after thyroidectomy and parathyroid autotransplantation involves temporary calcium and vitamin D replacement and close biochemical evaluation. This precautionary measure of parathyroid autotransplantation markedly reduces the incidence of permanent postoperative hypoparathyroidism. PMID:8651738

  3. Effects of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) on thyroid hormone and vitamin A levels in rats and mice

    Microsoft Academic Search

    Sara Hallgren; Taha Sinjari; Helen Hĺkansson; Per Darnerud

    2001-01-01

    The ability of the commercial polybrominated diphenyl ether (PBDE) preparation Bromkal 70-5 DE to alter thyroid hormone and vitamin A levels as well as microsomal enzyme activities was compared with that of the commercial polychlorinated biphenyl (PCB) preparation Aroclor 1254 in orally exposed female rats (Sprague-Dawley) and mice (C57BL\\/6 N). Additional mice were exposed to the PBDE congener 2,2',4,4'-tetrabromodiphenyl ether

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

    PubMed

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

    2014-02-25

    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

  5. A Novel Rat Model of Vitamin D Deficiency: Safe and Rapid Induction of Vitamin D and Calcitriol Deficiency without Hyperparathyroidism

    PubMed Central

    Stavenuiter, Andrea W. D.; Arcidiacono, Maria Vittoria; Ferrantelli, Evelina; Keuning, Eelco D.; Vila Cuenca, Marc; ter Wee, Piet M.; Beelen, Robert H. J.; Vervloet, Marc G.; Dusso, Adriana S.

    2015-01-01

    Vitamin D deficiency is associated with a range of clinical disorders. To study the mechanisms involved and improve treatments, animal models are tremendously useful. Current vitamin D deficient rat models have important practical limitations, including time requirements when using, exclusively, a vitamin D deficient diet. More importantly, induction of hypovitaminosis D causes significant fluctuations in parathyroid hormone (PTH) and mineral levels, complicating the interpretation of study results. To overcome these shortcomings, we report the successful induction of vitamin D deficiency within three weeks, with stable serum PTH and minerals levels, in Wistar rats. We incorporated two additional manoeuvres compared to a conventional diet. Firstly, the vitamin D depleted diet is calcium (Ca) enriched, to attenuate the development of secondary hyperparathyroidism. Secondly, six intraperitoneal injections of paricalcitol during the first two weeks are given to induce the rapid degradation of circulating vitamin D metabolites. After three weeks, serum 25-hydroxyvitamin D3 (25D) and 1,25-dihydroxyvitamin D3 (1,25D) levels had dropped below detection limits, with unchanged serum PTH, Ca, and phosphate (P) levels. Therefore, this model provides a useful tool to examine the sole effect of hypovitaminosis D, in a wide range of research settings, without confounding changes in PTH, Ca, and P. PMID:25815325

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

    PubMed Central

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

    2014-01-01

    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. PMID:25625100

  7. 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

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

    2014-01-01

    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

  8. Ectopic lipoadenoma of parathyroid

    PubMed Central

    Sanei, Mohammad Hossein; Naimi, Azar; Tabatabaei, Seyed Abbas

    2012-01-01

    A parathyroid lipoadenoma is a very rare cause of mediastinal mass. The clinical features of this pathologic entity is similar to those of the more common pathologic variants of parathyroid disease associated with primary hyperparathyroidism. A 58-year-old woman presented with huge multinodular goiter. Her thoracic CT scan was done before surgery, showed a posterior mediastinal mass. On microscopic examination, the thyroid was composed of thyroid follicles in varies sizes, compatible with a multinodular goiter and the mediastinal mass, microscopically, was composed of epithelial cells arranged in follicular and cellular nests pattern alter with abundant mature adipose tissue, morphologically closely resembled parathyroid tissue. Thyroid, mesenchymal and neuroendocrine origin for this tumor excluded by immunohistochemistry and the mass was diagnosed as a parathyroid lipoadenoma. In our case, there is a non functional parathyroid lipoadenoma with a very rare presence. PMID:23826002

  9. Vitamin D status and outcomes after renal transplantation.

    PubMed

    Bienaimé, Frank; Girard, Delphine; Anglicheau, Dany; Canaud, Guillaume; Souberbielle, Jean Claude; Kreis, Henri; Noël, Laure Hélčne; Friedlander, Gérard; Elie, Caroline; Legendre, Christophe; Prié, Dominique

    2013-04-01

    Kidney transplant recipients usually have low vitamin D levels, especially in the early posttransplantation period, but the association between vitamin D status with renal outcomes is not well described in this population. Here, we studied a prospective cohort of 634 kidney recipients who underwent transplantation at a single institution between January 2005 and June 2010. In this cohort, low 25-hydroxyvitamin D concentrations 3 months after transplantation did not predict early death or graft loss but were independently associated with lower measured GFR at 12 months (P=0.001) and higher risk for interstitial fibrosis and tubular atrophy (P=0.01). In contrast, levels of calcium, phosphorus, calcitriol, parathyroid hormone, or fibroblast growth factor-23 were not consistently associated with any of the studied outcomes. In conclusion, low 25-hydroxyvitamin D concentration measured 3 months after transplantation is an independent risk factor for interstitial fibrosis progression and is associated with a lower GFR 1 year after transplantation. PMID:23539758

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

    PubMed

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

    2000-05-01

    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

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

    PubMed

    Dobnig, H; Turner, R T

    1997-11-01

    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. PMID:9348185

  12. Functioning Oxyphil Adenoma of Parathyroid Gland

    PubMed Central

    McGregor, Douglas H.; Lotuaco, Luisa G.; Rao, M. S.; Chu, Luke L. H.

    1978-01-01

    Oxyphil cells and oxyphil cell adenomas of parathyroid glands are, in most instances, regarded to be nonfunctioning. Although 21 cases of hyperparathyroidism associated with parathyroid oxyphil cell adenoma have been reported, secretion of hormone by these tumors has not been conclusively demonstrated. A parathyroid adenoma, diagnosed by light microscopy as oxyphil type, together with the results from ultrastructural and biochemical studies of the patient's adenomatous tissue, are reported here. The patient, a 64-year-old male, was found to have elevated serum calcium, low serum phosphorus, and elevated serum immunoreactive parathormone: findings consistent with hyperparathyroidism. After excision of two small normal-appearing glands and one greatly enlarged (1.9 g) parathyroid gland, those laboratory values returned to normal. Light microscopy of the enlarged parathyroid indicated that it consisted almost entirely of an oxyphil adenoma. Electron microscopy revealed that the adenoma was composed mainly of mitochondria-rich oxyphil cells but also of interspersed transitional oxyphil cells and rare scattered chief cells. Golgi zones, rough endoplasmic reticulum, and prosecretory and secretory-like granules were observed in some oxyphil cells, in most transitional oxyphil cells, and in the infrequent chief cells. Thus, many of these cells appear to contribute to the production and secretion of parathormone. Biochemical studies performed directly on the adenomatous tissue demonstrated that it was able to synthesize proparathormone and parathormone, although the proportion of hormonal peptide synthesis relative to that of the total protein synthesis in this tissue was much smaller (0.9%) than that found in normal parathyroid tissue (5.7%). There was a small increase in immunoreactive parathormone when the adenoma tissue was incubated in a low-calcium medium. These findings indicate that this oxyphil adenoma of the parathyroid gland synthesized and secreted parathormone, apparently to some extent autonomously, but suggest that its capacity to do so was largely dependent on its component of cells other than fully developed oxyphil cells, such as transitional oxyphil cells. ImagesFigure 6Figure 7Figure 8Figure 1Figure 2Figure 3Figure 4Figure 9Figure 5Figure 10 PMID:686153

  13. In vivo distribution of parathyroid hormone receptors in bone: evidence that a predominant osseous target cell is not the mature osteoblast

    SciTech Connect

    Rouleau, M.F.; Mitchell, J.; Goltzman, D.

    1988-07-01

    Previous studies in vitro and in vivo have demonstrated the presence of receptor sites for PTH on cells of the osteoblast phenotype. Nevertheless, it is unclear whether the diverse functions of this hormone in bone can all be attributed to its interaction with a single cell type. In this study, we have used a radioautographic method to examine the competitive binding of /sup 125/I-labeled rat PTH-(1-34) to the long bones of rats in vivo. Our studies confirm the presence of competitive binding to mature osteoblasts and the absence of significant competitive binding to multinucleated osteoclasts. However, by light and electron microscopic radioautographic analysis, the majority of specific competitive PTH binding was present over a cell in the intertrabecular space of the metaphyseal region, which was distinct from the mature osteoblast. This large mononuclear cell with multiple cytoplasmic extensions appeared to interface with both the bone matrix and the microvascular osseous circulation and may provide an additional target to mediate hormonal effects on the skeleton.

  14. Fibroblast Growth Factor-23-mediated Inhibition of Renal Phosphate Transport in Mice Requires Sodium-Hydrogen Exchanger Regulatory Factor-1 (NHERF-1) and Synergizes with Parathyroid Hormone*

    PubMed Central

    Weinman, Edward J.; Steplock, Deborah; Shenolikar, Shirish; Biswas, Rajatsubhra

    2011-01-01

    Fibroblast growth factor-23 (FGF-23) inhibits sodium-dependent phosphate transport in brush border membrane vesicles derived from hormone-treated kidney slices of the mouse and in mouse proximal tubule cells by processes involving mitogen-activated protein kinase (MAPK) but not protein kinase A (PKA) or protein kinase C (PKC). By contrast, phosphate transport in brush border membrane vesicles and proximal tubule cells from sodium-hydrogen exchanger regulatory factor-1 (NHERF-1)-null mice were resistant to the inhibitory effect of FGF-23 (10?9 m). Infection of NHERF-1-null proximal tubule cells with wild-type adenovirus-GFP-NHERF-1 increased basal phosphate transport and restored the inhibitory effect of FGF-23. Infection with adenovirus-GFP-NHERF-1 containing a S77A or T95D mutation also increased basal phosphate transport, but the cells remained resistant to FGF-23 (10?9 m). Low concentrations of FGF-23 (10?13 m) and PTH (10?11 m) individually did not inhibit phosphate transport or activate PKA, PKC, or MAPK. When combined, however, these hormones markedly inhibited phosphate transport associated with activation of PKC and PKA but not MAPK. These studies indicate that FGF-23 inhibits phosphate transport in the mouse kidney by processes that involve the scaffold protein NHERF-1. In addition, FGF-23 synergizes with PTH to inhibit phosphate transport by facilitating the activation of the PTH signal transduction pathway. PMID:21908609

  15. Fat-Soluble Vitamin Status in Self-Neglecting Elderly

    NASA Technical Reports Server (NTRS)

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

    2006-01-01

    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.

  16. Differential Gene Expression by Oxyphil and Chief Cells of Human Parathyroid Glands

    PubMed Central

    Ritter, Cynthia S.; Haughey, Bruce H.; Miller, Brent

    2012-01-01

    Context: Parathyroid oxyphil cells, whose function is unknown, are thought to be derived from chief cells. Oxyphil cells increase in number in parathyroid glands of patients with chronic kidney disease (CKD) and are even more abundant in patients receiving treatment for hyperparathyroidism with calcitriol and/or the calcimimetic cinacalcet. Objective: We examined oxyphil and chief cells of parathyroid glands of CKD patients for differential expression of genes important to parathyroid function. Design/Setting/Participants: Parathyroid tissue from CKD patients with refractory hyperparathyroidism was immunostained for gene expression studies. Main Outcome Measure: Immunostaining for PTH, PTHrP, calcium-sensing receptor, glial cells missing 2, vitamin D receptor, 25-hydroxyvitamin D-1?-hydroxylase, and cytochrome c was quantified and expression reported for oxyphil and chief cells. Results: Expression of all proteins analyzed, except for the vitamin D receptor, was higher in oxyphil cells than in chief cells. Conclusion: Human parathyroid oxyphil cells express parathyroid-relevant genes found in the chief cells and have the potential to produce additional autocrine/paracrine factors, such as PTHrP and calcitriol. Additional studies are warranted to define the secretory properties of these cells and clarify their role in parathyroid pathophysiology. PMID:22585091

  17. The effect of cigarette smoke exposure on vitamin D level and biochemical parameters of mothers and neonates

    PubMed Central

    2013-01-01

    Background Exposure to cigarette smoke during pregnancy leads to several adverse effects on mother and child. The purpose of this study was to evaluate the effect of being a passive smoker during pregnancy on vitamin D level and related biochemical indices including parathyroid hormone, calcium, phosphorus and alkaline phosphatase in mothers and newborns. Methods One hundred eight pregnant women and their newborns participated in a historical cohort study in two equal groups (n?=?54) with and without cigarette smoke exposure. Maternal blood and urine samples and blood samples of umbilical cord were obtained in the delivery room. Concentration of 25-hydroxy vitamin D and related biochemical indices in samples of maternal and cord blood were investigated. Exposure to cigarette smoke was evaluated through questionnaire and maternal urine and umbilical cord serum cotinine levels. Results The mean level of 25-hydroxyvitamin D in maternal serum was 9.28?±?5.19?ng/mlin exposed and 10.75?±?5.26?ng/ml in non-exposed group(p?>?0.05). The mean concentration of 25-hydroxy vitamin D in cord serum was 10.83?±?6.68?ng/ml in the exposed and 11.05?±?4.99?ng/ml in the non-exposed group(p?>?0.05). The exposed mothers had significantly higher parathyroid hormone level (p?=?0.013), lower serum calcium (p?=?0.024) and higher serum alkaline phosphatase (p?=?0.024). There was a significant correlation between maternal and umbilical cord serum 25-hydroxyvitamin D within both exposed and non-exposed groups (p?parathyroid hormone and alkaline phosphatase in mothers. PMID:23663478

  18. Hyperparathyroidism caused by a functional parathyroid cyst

    PubMed Central

    Suzuki, Kunihiro; Sakuta, Ayuko; Aoki, Chie; Aso, Yosimasa

    2013-01-01

    A 67-year-old Japanese woman was admitted to our hospital for malaise and loss of appetite. Relevant biochemical examinations showed definite hypercalcaemia and elevated serum levels of intact parathyroid hormone (PTH). We performed thyroid ultrasonography and CT of the neck, which revealed a cystic lesion in the right lower lobe of the thyroid glands. Ultrasound-guided fine-needle aspiration was performed, and PTH level of the cystic fluid was markedly elevated. Technetium-99m-hexakis 2-methoxyisobutyi isonitrile sesta scintigraphy showed intense ring-shaped accumulation of radioactivity in the wall of the cyst. The patient underwent a right lobectomy to resect the cystic parathyroid adenoma. After surgery, her serum calcium and PTH level returned to normal ranges. PMID:23813580

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

    PubMed Central

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

    2014-01-01

    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

  20. Prognosis of parathyroid function after successful percutaneous ethanol injection therapy guided by color doppler flow mapping in chronic dialysis patients

    Microsoft Academic Search

    Takatoshi Kakuta; Masafumi Fukagawa; Tomotaka Fujisaki; Miho Hida; Hajime Suzuki; Hideto Sakai; Kiyoshi Kurokawa; Akira Saito

    1999-01-01

    Selective percutaneous ethanol injection therapy (PEIT) of the parathyroid glands has been shown to be effective in chronic dialysis patients with severe secondary hyperparathyroidism. In this study, we examined whether it was possible to maintain parathyroid function within target range (intact parathyroid hormone [iPTH], 160 to 360 pg\\/mL) in the long term after successful destruction of hyperplastic tissue. PEIT was

  1. Spontaneous cervical haemorrhage of a parathyroid adenoma

    PubMed Central

    Knee, Graham; Todd, Colin

    2015-01-01

    Summary Haemorrhage of a parathyroid adenoma is a rare clinical presentation. This report describes a previously fit and well 54-year-old woman who presented with acute neck swelling and pain with an overlying ecchymosis. Admission laboratory tests revealed a raised parathyroid hormone and hypercalcaemia. A computed tomography (CT) scan showed widespread anterior cervical haemorrhage and a lesion at the inferior pole of the left thyroid gland. A working diagnosis of spontaneous haemorrhage from a parathyroid adenoma was made. As she was haemodynamically stable, she was treated conservatively with a period of observation in hospital to monitor for signs of neck organ compression. Follow-up imaging with CT, ultrasound and sestamibi confirmed the likely source of haemorrhage as a parathyroid nodule with significant vascularity. The diagnosis was confirmed on histopathological analysis after elective surgical exploration of the neck 6 months after her presentation. This revealed a benign parathyroid adenoma with evidence of acute and chronic bleeding. The patient made a full recovery with immediate normalisation of her biochemistry post-operatively. Despite developing a hoarse voice in the immediate post-operative period, this resolved completely within 1 month. This case report provides further evidence to support a minimal delay for elective surgery after conservative management to reduce the risks associated with recurrent bleeding. Learning points Haemorrhage of a parathyroid adenoma should be a differential for all cases of acute cervical swelling or ecchymosis with no precipitating factor.The clerking should identify any risk factors for endocrine disease.Blood tests to screen for abnormal parathyroid biochemistry should be performed on admission.Detailed imaging of the neck is essential to identify the source of haemorrhage and risk of compression to vital neck organs.Conservative management is a suitable option for patients who remain haemodynamically stable but all should undergo a period of observation in hospital.Conservatively managed patients should be considered for definitive surgical exploration within a month of presentation to avoid the risks of recurrent bleeding. PMID:26124955

  2. Glucocorticoids and 1,25-dihydroxyvitamin D3 regulate parathyroid hormone stimulation of adenosine 3',5'-monophosphate-dependent protein kinase in rat osteosarcoma cells.

    PubMed

    Titus, L; Rubin, J E; Lorang, M T; Catherwood, B D

    1988-09-01

    Glucocorticoids increase and 1,25-dihydoxyvitamin D3 [1,25-(OH)2D3] decreases the activity of PTH-responsive adenylate cyclase, altering intracellular cAMP in a rat osteoblast-like cell line (ROS 17/2.8). This study was undertaken to measure the subsequent activation of the cAMP-dependent protein kinase (PKA). Pretreatment of ROS cells for 2 days with the glucocorticoid triamcinolone acetonide (TRM), shifted the dose-response curve for PKA activation by PTH upward compared to the control value. Basal PKA activity was enhanced 50% by TRM, and the PTH concentration required for maximal activation of PKA decreased from 1.0 to 0.05 ng/ml. At the lowest effective PTH concentration (0.05 ng/ml) the mean PKA activity ratio increased to 0.73 in TRM-treated cells compared with 0.45 in untreated cells. Pretreatment with 1,25-(OH)2D3 had opposite effects, shifting the dose-response curve for PKA activation by PTH downward and to the right, decreasing the basal activity ratio from 0.26 to 0.16, and increasing the PTH concentration required for maximal activation to 10 ng/ml. 1,25-(OH)2D3-treated cells stimulated with 0.5-1 ng/ml PTH consistently had lower PKA activity ratios than untreated cells. Simultaneous treatment with 1,25-(OH)2D3 reversed the effect of TRM. There were no differences in total PKA activity (2.57 +/- 0.09 pmol 32P/min.micrograms protein) between treatment groups, suggesting that TRM and 1,25-(OH)2D3 do not alter the cellular PKA concentration. In control experiments exogenous PKA was added to sonication buffer of PTH-stimulated cells to verify that the TRM and 1,25-(OH)2D3 shifts in PKA activation at low PTH doses occur before sonication. cAMP-dependent protein kinase activation was also studied by measuring the progressive occupation of regulatory subunit-binding sites by hormonally stimulated endogenous cAMP. [3H] cAMP binding was expressed as the percent change in bound [3H]cAMP per microgram protein compared to that in unstimulated cells not steroid treated. [3H]cAMP binding to all cytosol fractions decreased as PTH increased over the concentration range predicted by our PKA activation experiments. TRM treatment shifted the curve for [3H]cAMP binding to regulatory subunit downward and to the left, and 1,25-(OH)2D3 treatment shifted it upward and to the right. In cells treated with both TRM and 1,25-(OH)2D3, the curve was similar to control curve. Sonicating unstimulated cells in buffer containing comparable concentrations of added cAMP did not alter [3H]cAMP binding. These and the previous controls suggest that changes in PKA activation at low doses of PKA reflect cellular events occurring before cell disruption.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2456915

  3. Health outcomes of vitamin D. Part I. characteristics and classic role.

    PubMed

    Wranicz, Julia; Szostak-W?gierek, Dorota

    2014-01-01

    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

  4. Vitamin D Deficiency and Secondary Hyperparathyroidism Are Common Complications in Patients with Peripheral Arterial Disease

    PubMed Central

    Fahrleitner, Astrid; Dobnig, Harald; Obernosterer, Andrea; Pilger, Ernst; Leb, Georg; Weber, Kurt; Kudlacek, Stefan; Obermayer-Pietsch, Barbara M

    2002-01-01

    OBJECTIVE To investigate via the vitamin D status whether patients with peripheral arterial disease (PAD) tend to develop vitamin D deficiency that in turn influences their clinical symptoms. DESIGN Cross-sectional. SETTING University hospital. PATIENTS AND PARTICIPANTS Three hundred twenty-seven patients were evaluated; subjects with secondary causes of bone disease or bone active medication were excluded. One hundred sixty-one patients with either PAD stage II (n = 84) or stage IV (n = 77) were enrolled and compared to 45 age- and sex-matched healthy controls. MEASUREMENTS AND MAIN RESULTS All patients underwent determinations of serum chemistry, 25-hydroxyvitamin D (vitamin D3) intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), and osteocalcin and were further stratified according to an individual restriction score into 3 groups: mildly, moderately, or severely restricted in daily life due to the underlying disease. Patients with PAD IV showed significantly lower vitamin D3 (P = .0001), and calcium (P = .0001) values and significantly higher iPTH (P = .0001), osteocalcin (P = .0001) and ALP (P = .02) levels as compared to patients with PAD II. Patients considering themselves as severely restricted due to the underlying disease showed lower vitamin D3 and higher iPTH levels than those who described only a moderate (vitamin D3: P < .001; iPTH: P < .01) or mild (vitamin D3: P < .001; iPTH: P < .001) restriction in daily life. CONCLUSION Patients with PAD IV, especially those who feel severely restricted due to the disease, are at high risk of developing vitamin D deficiency, secondary hyperparathyroidism, and ultimately osteomalacia due to immobilization and subsequent lack of exposure to sunlight, all of which in turn lead to further deterioration. Monitoring of vitamin D metabolism and vitamin D replacement therapy could be a simple, inexpensive approach to mitigating clinical symptoms and improving quality of life in patients with advanced PAD. PMID:12220361

  5. 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

    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

    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

  6. A difficult case of mediastinal parathyroid adenoma: theoretical and clinical considerations.

    PubMed

    Lunc?, S; St?nescu, C; Bouras, G; Vix, M; Marescaux, J

    2004-01-01

    About one quarter of patients with primary hyperparathyroidism have ectopic parathyroid tissue. The majority of parathyroid glands can be reached through a cervical approach, but in about 2% of the cases the ectopic gland is in the mediastinum in a location that requires a thoracic approach. Failure to remove ectopic mediastinal parathyroid tissue results in persistent hyperparathyroidism. Reoperative exploration for persistent hyperparathyroidism is often difficult even in the hands of experienced surgeons. Recent advances in preoperative localization techniques and intraoperative parathyroid hormone measurement have improved the rates of successful resection. We present a difficult case of persistent hyperparathyroidism secondary to an ectopic middle mediastinal parathyroid adenoma, which was eventually successfully managed in a specialised unit. PMID:15739675

  7. Parathyroid hormone-related protein blood test

    MedlinePLUS

    PTHrp; PTH-related peptide ... calcium level is caused by an increase in PTH-related protein. ... No detectable (or minimal) PTH-like protein is normal. Women who are breastfeeding may have detectable PTH-related protein values. The examples above are common ...

  8. Association of the CYP24A1-rs2296241 polymorphism of the vitamin D catabolism enzyme with hormone-related cancer risk: a meta-analysis

    PubMed Central

    Wang, Ping; Zhang, Hemei; Zhang, Zengli; Qin, Liqiang; Li, Bingyan

    2015-01-01

    Background The evidence for vitamin D reducing cancer risk is inconsistent, and it is not clear whether this reduction is related to variation in cytochrome P450 (CYP)24A1, the only enzyme known to degrade active vitamin D. We focused on evaluating the association of CYP24A1-rs2296241 polymorphism with hormone-related cancer risk by conducting a meta-analysis. Methods A systematic literature search was conducted in April 2014 (updated in December 2014) to identify eligible studies. A random-effects model was used to pool the odds ratio (OR). Results Eleven studies including 5,145 cases and 5,136 controls were considered for the allelic model, and eight studies of 3,959 cases and 3,560 controls were utilized for the additive, recessive, and dominant models. There was no significant association between CYP24A1-rs2296241 and hormone-related cancer risk in any of the models, yet substantial heterogeneity was observed. Subgroup analyses indicated that CYP24A1-rs2296241 variation reduced the prostate cancer risk in the additive (OR 0.91, 95% confidence interval 0.85–0.97) and recessive (OR 0.80, 95% confidence interval 0.67–0.95) models, with no evidence of heterogeneity. Conclusion This meta-analysis indicated that CYP24A1-rs2296241 polymorphism reduced the androgen-related prostate cancer risk in additive and recessive models. More genetic loci are needed to confirm the effect of CYP24A1 variation on the risk of prostate cancer. PMID:26045671

  9. Modified-release oral calcifediol corrects vitamin D insufficiency with minimal CYP24A1 upregulation.

    PubMed

    Petkovich, Martin; Melnick, Joel; White, Jay; Tabash, Samir; Strugnell, Stephen; Bishop, Charles W

    2015-04-01

    Vitamin D insufficiency is prevalent in chronic kidney disease (CKD) and associated with secondary hyperparathyroidism (SHPT) and increased risk of bone and vascular disease. Unfortunately, supplementation of stage 3 or 4 CKD patients with currently recommended vitamin D2 or D3 regimens does not reliably restore serum total 25-hydroxyvitamin D to adequacy (?30ng/mL) or effectively control SHPT. Preclinical and clinical studies were conducted to evaluate whether the effectiveness of vitamin D repletion depends, at least in part, on the rate of repletion. A modified-release (MR) oral formulation of calcifediol (25-hydroxyvitamin D3) was developed which raised serum 25-hydroxyvitamin D3 and calcitriol levels gradually. Single doses of either bolus intravenous (IV) or oral MR calcifediol were administered to vitamin D deficient rats. Bolus IV calcifediol produced rapid increases in serum 25-hydroxyvitamin D3, calcitriol and FGF23, along with significant induction of CYP24A1 in both kidney and parathyroid gland. In contrast, oral MR calcifediol produced gradual increases in serum 25-hydroxyvitamin D3 and calcitriol and achieved similar hormonal exposure, yet neither CYP24A1 nor FGF23 were induced. A 10-fold greater exposure to bolus IV than oral MR calcifediol was required to similarly lower intact parathyroid hormone (iPTH). Single doses of oral MR (450 or 900?g) or bolus IV (450?g) calcifediol were administered to patients with stage 3 or 4 CKD, SHPT and vitamin D insufficiency. Changes in serum 25-hydroxyvitamin D3 and calcitriol and in plasma iPTH were determined at multiple time-points over the following 42 days. IV calcifediol produced abrupt and pronounced increases in serum 25-hydroxyvitamin D3 and calcitriol, but little change in plasma iPTH. As in animals, these surges triggered increased vitamin D catabolism, as evidenced by elevated production of 24,25-dihydroxyvitamin D3. In contrast, MR calcifediol raised serum 25-hydroxyvitamin D3 and calcitriol gradually, and meaningfully lowered plasma iPTH levels. Taken together, these studies indicate that rapid increases in 25-hydroxyvitamin D3 trigger CYP24A1 and FGF23 induction, limiting effective exposure to calcitriol and iPTH reduction in SHPT. They also support further investigation of gradual vitamin D repletion for improved clinical effectiveness. This article is part of a Special Issue entitled "17th Vitamin D Workshop". PMID:25446887

  10. FGF23 and the parathyroid.

    PubMed

    Silver, Justin; Naveh-Many, Tally

    2012-01-01

    Klotho and fibroblast growth factor 1 (FGFR1) are expressed not only in FGF23's classical target organ, the kidney, but also in other organs such as the parathyroid. FGF23 acts on the parathyroid to decrease PTH mRNA and serum PTH levels. It does this by activating the MAPK pathway. In chronic kidney disease there are very high levels of serum FGF23 together with increased serum PTH levels, implying resistance of the parathyroid to the action of FGF23. This has been shown in parathyroid tissue surgically removed from dialysis patients as well as in experimental models of uremia to be due to down-regulation of klotho-FGFR1 expression in the parathyroid. Moreover, the parathyroids of rats with advanced uremia do not respond to administered FGF23 by activation of the MAPK pathway or inhibition of PTH secretion. Therefore, there is down-regulation of parathyroid klotho-FGFR1 in CKD which correlates with the resistance of the parathyroid to FGF23. A further subject of great interest in this field is the effect of PTH to directly increase FGF23 expression by osteoblast like cells in culture and the observations that parathyroidectomy prevents and corrects the increased serum FGF23 level of experimental CKD as well as decreases FGF23 in patients with CKD. There is therefore a negative feedback loop between bone and the parathyroid. PMID:22396164

  11. Vitamin D Test

    MedlinePLUS

    ... produce excess amounts of vitamin D, such as sarcoidosis or some forms of lymphoma (because immune cells ... hormone or when there are diseases, such as sarcoidosis or some lymphomas , that can make 1,25- ...

  12. Interactions Between Adrenal and Calcium-Regulatory Hormones in Human Health

    PubMed Central

    Brown, Jenifer M.; Vaidya, Anand

    2014-01-01

    Purpose of Review To summarize evidence characterizing the interactions between adrenal- and calcium-regulating hormones, and the relevance of these interactions to human cardiovascular and skeletal health. Recent Findings Human studies support the regulation of parathyroid hormone (PTH) by the renin-angiotensin-aldosterone system (RAAS): angiotensin II may stimulate PTH secretion via an acute and direct mechanism, whereas aldosterone may exert a chronic stimulation of PTH secretion. Studies in primary aldosteronism, congestive heart failure, and chronic kidney disease have identified associations between hyperaldosteronism, hyperparathyroidism, and bone loss, which appear to improve when inhibiting the RAAS. Conversely, elevated PTH and insufficient vitamin D status have been associated with adverse cardiovascular outcomes, which may be mediated by the RAAS. Studies of primary hyperparathyroidism implicate PTH-mediated stimulation of the RAAS, and recent evidence shows that the vitamin D-vitamin D receptor (VDR) complex may negatively regulate renin expression and RAAS activity. Ongoing human interventional studies are evaluating the influence of RAAS inhibition on PTH and the influence of VDR agonists on RAAS activity. Summary While previously considered independent endocrine systems, emerging evidence supports a complex web of interactions between adrenal and calcium-regulating hormones, with implications for human cardiovascular and skeletal health. PMID:24694551

  13. Calcitonin, the forgotten hormone: does it deserve to be forgotten?

    PubMed Central

    Felsenfeld, Arnold J.; Levine, Barton S.

    2015-01-01

    Calcitonin is a 32 amino acid hormone secreted by the C-cells of the thyroid gland. Calcitonin has been preserved during the transition from ocean-based life to land dwellers and is phylogenetically older than parathyroid hormone. Calcitonin secretion is stimulated by increases in the serum calcium concentration and calcitonin protects against the development of hypercalcemia. Calcitonin is also stimulated by gastrointestinal hormones such as gastrin. This has led to the unproven hypothesis that postprandial calcitonin stimulation could play a role in the deposition of calcium and phosphate in bone after feeding. However, no bone or other abnormalities have been described in states of calcitonin deficiency or excess except for diarrhea in a few patients with medullary thyroid carcinoma. Calcitonin is known to stimulate renal 1,25 (OH)2 vitamin D (1,25D) production at a site in the proximal tubule different from parathyroid hormone and hypophosphatemia. During pregnancy and lactation, both calcitonin and 1,25D are increased. The increases in calcitonin and 1,25D may be important in the transfer of maternal calcium to the fetus/infant and in the prevention and recovery of maternal bone loss. Calcitonin has an immediate effect on decreasing osteoclast activity and has been used for treatment of hypercalcemia. Recent studies in the calcitonin gene knockout mouse have shown increases in bone mass and bone formation. This last result together with the presence of calcitonin receptors on the osteocyte suggests that calcitonin could possibly affect osteocyte products which affect bone formation. In summary, a precise role for calcitonin remains elusive more than 50 years after its discovery. PMID:25815174

  14. Leaf Vitamin C Contents Modulate Plant Defense Transcripts and Regulate Genes That Control Development through Hormone SignalingW?

    PubMed Central

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

    2003-01-01

    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 type. Many defense genes are activated, particularly those that encode pathogenesis-related proteins. Furthermore, transcript changes indicate that growth and development are constrained in vtc1 by the modulation of abscisic acid signaling. Abscisic acid contents are significantly higher in vtc1 than in the wild type. Key features of the molecular signature of ascorbate deficiency can be reversed by incubating vtc1 leaf discs in ascorbate. This finding provides evidence that many of the observed effects on transcript abundance in vtc1 result from ascorbate deficiency. Hence, through modifying gene expression, vitamin C contents not only act to regulate defense and survival but also act via phytohormones to modulate plant growth under optimal conditions. PMID:12671089

  15. Parathyroid hyperplasia associated with thymoma.

    PubMed Central

    Byrne, D. J.; Gunn, A.; Davidson, D. L.; Paterson, C. R.

    1989-01-01

    The case of a 65 year old female with myasthenia gravis and hypercalcaemia is presented. Failure of medical control of the myasthenia necessitated thymectomy at which time parathyroid exploration was also carried out. This revealed parathyroid hyperplasia and a thymoma. This association has not been previously documented in the literature. PMID:2608566

  16. Alterations of calcium metabolism and of parathyroid function in primary aldosteronism, and their reversal by spironolactone or by surgical removal of aldosterone-producing adenomas

    Microsoft Academic Search

    Ermanno Rossi; Carlo Sani; Franco Perazzoli; Maria Cristina Casoli; Aurelio Negro; Claudio Dotti

    1995-01-01

    In order to investigate the possible existence of abnormal calcium metabolism and parathyroid function in primary aldosteronism (PA), we have compared the calcium\\/parathyroid hormone (PTH) profile of patients with PA with the profile of healthy normotensive subjects and of patients with essential hypertension (EH). Furthermore, we have evaluated the effects of spironolactone and the surgical removal of aldosterone-producing adenomas on

  17. Sequence elements in the human osteocalcin gene confer basal activation and inducible response to hormonal vitamin D sub 3

    SciTech Connect

    Kerner, S.A.; Scott, R.A.; Pike, J.W. (Baylor College of Medicine, Houston, TX (USA))

    1989-06-01

    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.

  18. Iatrogenic vitamin D toxicity in an infant--a case report and review of literature.

    PubMed

    Ketha, Hemamalini; Wadams, Heather; Lteif, Aida; Singh, Ravinder J

    2015-04-01

    Public concern over vitamin D deficiency has led to widespread use of over the counter (OTC) vitamin D (-D3 or -D2) supplements, containing up to 10,000 IU/unit dose (400 IU=10?g). Overzealous use of such supplements can cause hypercalcemia due to vitamin D toxicity. Infants are particularly vulnerable to toxicity associated with vitamin D overdose. OTC supplements are not subject to stringent quality control regulations from FDA and high degree of variability in vitamin D content in OTC pills has been demonstrated. Other etiologies of vitamin D induced hypercalcemia include hyperparathyroidism, granulomatous malignancies like sarcoidosis and mutations in the CYP24A1 gene. The differential diagnosis of hypercalcemia should include iatrogenic and genetic etiologies. C24-hydroxylation and C3-epimerization are two important biochemical pathways via which 25-hydroxyvitamin D3 (25(OH)D3) is converted to its metabolites, 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) or its C3 epimer, 3-epi-25-OH-D3 respectively. Mutations in the CYP24A1 gene cause reduced serum 24,25(OH)2D3 to 25(OH)D3 ratio (<0.02), elevated serum 1,25-dihydroxyvitamin D (1,25(OH)2D3), hypercalcemia, hypercalciuria and nephrolithiasis. Studies in infants have shown that 3-epi-25(OH)D3 can contribute 9-61.1% of the total 25(OH)D3. Therefore, measurements of parathyroid hormone (PTH) and vitamin D metabolites 25(OH)D3, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3 are useful to investigate whether the underlying cause of vitamin D toxicity is iatrogenic versus genetic. Here we report a case of vitamin D3 associated toxicity in a 4-month-old female who was exclusively breast-fed and received an oral liquid vitamin D3 supplement at a dose significantly higher than recommended on the label. The vitamin D3 content of the supplement was threefold higher (6000 IU of D/drop) than listed on the label (2000 IU). Due to overdosing and higher vitamin D3 content, the infant received ?50,000 IU/day for two months resulting in severe hypercalcemia, hypercalciuria and nephrocalcinosis. We also review the relevant literature on vitamin D3 toxicity in this report. PMID:25636720

  19. [Surgical resection of the thyroid and parathyroid glands].

    PubMed

    Woenckhaus, U; Büttner, R; Bollheimer, L C

    2007-06-01

    The main indication for surgery of the thyroid gland is the resection of nodular, suspicious or hyperfunctioning tissue. Following thyroidectomy, L-thyroxine therapy is initiated adjusted to the remnant thyroid function. To prevent recurrence of a multinodular goiter, supplementation with iodine is strongly recommended. The management of patients with differentiated thyroid cancer depends on risk stratification. Although large prospective studies are missing, low-risk patients probably do not benefit from total thyroid ablation and lifelong thyroxine suppression therapy. As a result of impaired parathyroid function or resection of the parathyroid glands for hyperparathyroidism, acute or chronic hypocalcaemia can develop. If treatment with oral calcium is insufficient, the addition of a vitamin D analogue is necessary. This requires close monitoring to avoid renal or other hypercalcaemic complications. PMID:17497113

  20. Age-related changes of the ultrastrucure in the parathyroid gland of the golden hamster.

    PubMed

    Utsumi, Michiya; Moriguchi, Keiichi; Kato, Akiko; Maeda, Hatsuhiko; Ohno, Norikazu

    2014-01-01

    We qualitatively and quantitatively investigated the parathyroid glands of golden hamsters aged 6, 12, 18, 24 and 30 months. Percent area of rER in the parathyroid gland in golden hamsters at 24 months of age was significantly higher when compared to 6 and 12 months of age, and the percent area at 30 months of age was significantly higher when compared to 12 months of age, but there were no significant differences between 24 and 30 months of age. Percent area of the Golgi apparatus at 24 and 30 months of age was significantly higher when compared to 6, 12 and 18 months of age. Ultrastructurally, we believe that in the parathyroid gland of the golden hamster, synthesis and release of parathyroid hormone increase gradually from 6 to 24months of age and are maintained from 24 to 30 months of age. PMID:25492843

  1. Vitamin D level: is it related to disease activity in inflammatory joint disease?

    PubMed

    Braun-Moscovici, Yolanda; Toledano, K; Markovits, D; Rozin, A; Nahir, A M; Balbir-Gurman, A

    2011-04-01

    The objectives of this study are to assess the vitamin D status in patients (pts) with inflammatory joint diseases (IJD), and its correlation with disease activity. 121 consecutive pts (85 rheumatoid arthritis (RA), 22 psoriatic arthritis (PSA), 14 ankylosing spondylitis (AS)) underwent clinical and laboratory evaluation which included kidney and liver function tests, serum calcium and phosphor levels, 25(OH)D and parathyroid hormone (PTH). Disease activity was assessed by DAS 28 in RA and PSA pts and by BASDAI in AS pts, sedimentation rate (ESR) and CRP. According to activity indexes, pts were divided into subgroups with low (DAS28 < 3.2 and BASDAI < 4), and moderate-to-high disease activity (DAS28 > 3.2 and BASDAI > 4). Associations between serum levels of 25(OH)D and age, gender, ethnicity, type and disease duration, treatment, (anti-tumor necrosis factor? (TNF?) agents or DMARDs), seasonal variations, and disease activity were assessed. Vitamin D deficiency was found in 51 pts (42.1%). The incidence was higher among Arab pts (76.7%) compared to Jews (23%). The difference of 25(OH)D levels between Arabs (mean 9.4 ± 4.2 ng/ml) and Jews (mean 17.8 ± 8.4 ng/ml) was statistically significant (p < 0.0001). We did not find correlation between vitamin D levels and the other evaluated factors. A surprisingly high incidence of vitamin D deficiency was found in IJD patients in a sunny Mediterranean country. This finding justifies the inclusion of vitamin D in the routine lab work-up of pts with IJD. The only statistical significant correlation was found between vitamin D level and ethnic origin. Further studies are needed to look for genetic polymorphism of vitamin D receptors. PMID:20033415

  2. Inferences from genetically modified mouse models on the skeletal actions of vitamin D.

    PubMed

    Goltzman, D

    2015-04-01

    Vitamin D has pleiotropic extra-skeletal effects which have been noted in mouse models of deletion of either the 25-hydroxy vitamin D 1?-hydroxylase enzyme, cyp27b1 (1OHase(-/-) mice) or of the vitamin D receptor (Vdr(-/-) mice); these may be preventable or reversible by either restoring normal signaling of the 1,25(OH)2D/VDR system, or in some cases by restoring normal mineral homeostasis. However, effects on skeletal and mineral homeostasis are clearly the major phenotype observed in humans with loss-of-function mutations in either CYP27B1 or VDR. In mouse phenocopies of these human disorders, correction of hypocalcemia and hypophosphatemia reduce elevated circulating parathyroid hormone concentrations and normalize impaired bone mineralization, but restoration of normal 1,25(OH)2D/VDR signaling may be required for optimal bone formation. Induction of high endogenous 1,25(OH)2D concentrations in genetically modified mouse models may cause increased bone resorption and decreased mineralization. Transgenic Vdr overexpression and conditional Vdr deletion in cells of the osteoblastic lineage have also provided insights into the stages of osteoblast differentiation which may mediate these actions. These anabolic and catabolic effects of the 1,25(OH)2D system on bone may therefore be a function of both the ambient concentration of circulating 1,25(OH)2D and the stage of differentiation of the osteoblast. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. PMID:25237033

  3. Vitamin D3 supplementation for 16 weeks improves flow-mediated dilation in overweight African American adults

    PubMed Central

    Harris, Ryan A; Pedersen-White, Jennifer; Guo, De-Huang; Stallmann-Jorgensen, Inger S.; Keeton, Daniel; Huang, Ying; Shah, Yashesh; Zhu, Haidong; Dong, Yanbin

    2013-01-01

    Background A growing body of evidence has linked vitamin D deficiency to increased risk of cardiovascular disease. Vitamin D deficiency is also more common in African Americans for whom an increased cardiovascular disease risk exists. This study sought to test the hypothesis that 16 weeks of 60,000 IU monthly supplementation of oral vitamin D3 would improve flow-mediated dilation (FMD) in African Americans, whereas no change would be observed in the placebo group. Methods A randomized, double blind, placebo controlled clinical trial was conducted. Fifty-seven African American adults were randomly assigned to either the placebo group or vitamin D group. Results Following 16 weeks of placebo (n=23; mean age 31±2 years) or 60,000 IU monthly oral vitamin D3 (n=22; mean age 29±2 years), serum concentrations of 25 hydroxyvitamin D increased from 38.2±3.0 nmol/L to 48.7±3.2 nmol/L and 34.3±2.2 nmol/L to 100.9±6.6 nmol/L, respectively. No changes in serum parathyroid hormone, serum calcium, or urine calcium/creatinine were observed following either treatment. Following 16 weeks of treatment, significant improvements in FMD were only observed in the vitamin D group (1.8±1.3%), whereas the placebo group had no change (-1.3±0.6%). Similarly, the vitamin D group exhibited an increase in absolute change in diameter (0.005±0.004 cm) and FMD/shear (0.08±0.04 %/s-1, AUC × 103) following treatment, whereas no change (-0.005±0.002 cm and -0.02±0.02 %/s-1, AUC, respectively) was observed following placebo. Conclusions Supplementation of 60,000 IU monthly oral vitamin D3 (~2000 IU per day) for 16 weeks is effective at improving vascular endothelial function in African American adults. PMID:21311504

  4. Calcium metabolism and vitamin D in the extreme longevity

    PubMed Central

    Passeri, Giovanni; Vescovini, Rosanna; Sansoni, Paolo; Galli, Carlo; Franceschi, Claudio; Passeri, Mario

    2009-01-01

    Skeletal remodelling is a continuous process during life and is still active also in extreme senescence. In the elderly, bone resorption often prevails over bone formation, causing bone loss and fragility. Elderly subjects are exposed to the risk of fractures, and loss of self-sufficiency, if considering that the proximal femur is the most frequently involved site. Bone remodelling can maintain circulating calcium within physiological ranges, at the expense of a substantial loss of this ion from the skeleton, particularly during senescence. Calcium metabolism is regulated at cellular/molecular level by a network of cytokines, growth factors, systemic hormones that act on bone in paracrine/autocrine/systemic fashion. Among the molecules involved in bone metabolism, parathyroid hormone (PTH) and vitamin D present some peculiar aspects during senescence. The osteometabolic features in a consistent group of centenarians have been evaluated. It results that a severe hypovitaminosis D was present in 99 out of 104 centenarians (25-OH vitamin D below 5 nmol/L), and that it plays an important role as a factor inducing a vicious circle involving hypocalcemia, secondary hyperparathyroidism, together with biochemical features indicating a consistent bone loss. Serum C-terminal cross-linking telopeptide, a specific marker of bone resorption was elevated in 92% of these subjects. Moreover, it has been found that several femoral fractures had occurred after 90 years of age. These data offer a rational for the possible prevention of elevated bone turnover, bone loss and consequently the reduction of osteoporotic fractures and fractures-induced disability, in the oldest olds, through the simple supplementation with calcium and vitamin D. PMID:17698310

  5. A Case Report of 20 Lung Radiofrequency Ablation Sessions for 50 Lung Metastases from Parathyroid Carcinoma Causing Hyperparathyroidism

    SciTech Connect

    Tochio, Maki, E-mail: m-tochio@clin.medic.mie-u.ac.jp; Takaki, Haruyuki; Yamakado, Koichiro; Uraki, Junji; Kashima, Masataka; Nakatsuka, Atsuhiro [Mie University School of Medicine, Department of Radiology (Japan); Takao, Motoshi; Shimamoto, Akira; Tarukawa, Tomohito; Shimpo, Hideto [Mie University School of Medicine, Department of Thoracic and Cardiovascular Surgery (Japan); Takeda, Kan [Mie University School of Medicine, Department of Radiology (Japan)

    2010-06-15

    A 47-year-old man presented with multiple lung metastases from parathyroid carcinoma that caused hyperparathyroidism and refractory hypercalcemia. Lung radiofrequency (RF) ablation was repeated to decrease the serum calcium and parathyroid hormone levels and improve general fatigue. Pulmonary resection was combined for lung hilum metastases. The patient is still alive 4 years after the initial RF session. He has received 20 RF sessions for 50 lung metastases during this period.

  6. Synchronous parathyroid adenoma and thyroid papillary carcinoma: a case report.

    PubMed

    Iakovou, Ioannis P; Konstantinidis, Iordanis E; Chrisoulidou, Alexandra I; Doumas, Argyrios S

    2009-01-01

    A 51-year-old female patient presented with atypical chest pain, laryngo-oesophageal reflux, increased levels of serum calcium and parathyroid hormone. Ultrasonography showed a multinodular goiter with a prominent solid nodule in the lower left thyroid lobe and a solid hypoechoic nodule outside this area.Tc99m-sestamibi parathyroid scintigraphy was performed to investigate a primary hyperparathyroidism, revealing an area with increased uptake in the lower left thyroid lobe and another area with marked uptake lower than this level. Thyroid scintigraphy with 99mTc showed a cold nodule of the left lower pole. FNA of the thyroid nodule was positive for papillary carcinoma later verified by postoperative histopathology.This case underlines the need for a clinical high index of suspicion for synchronous hyperparathyroidism and thyroid cancer. PMID:20062698

  7. Synchronous parathyroid adenoma and thyroid papillary carcinoma: a case report

    PubMed Central

    2009-01-01

    A 51-year-old female patient presented with atypical chest pain, laryngo-oesophageal reflux, increased levels of serum calcium and parathyroid hormone. Ultrasonography showed a multinodular goiter with a prominent solid nodule in the lower left thyroid lobe and a solid hypoechoic nodule outside this area. Tc99m-sestamibi parathyroid scintigraphy was performed to investigate a primary hyperparathyroidism, revealing an area with increased uptake in the lower left thyroid lobe and another area with marked uptake lower than this level. Thyroid scintigraphy with 99mTc showed a cold nodule of the left lower pole. FNA of the thyroid nodule was positive for papillary carcinoma later verified by postoperative histopathology. This case underlines the need for a clinical high index of suspicion for synchronous hyperparathyroidism and thyroid cancer. PMID:20062698

  8. [Mediastinal parathyroid adenoma: a surgically treated case].

    PubMed

    Mészáros, László; Kajdácsi, Zita; Tóth, Miklós; Révai, Tamás; Vadász, Pál

    2013-08-01

    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

  9. The effect of metabolic acidosis on vitamin D metabolites and bone histology in uremic rats.

    PubMed

    Chan, Y L; Savdie, E; Mason, R S; Posen, S

    1985-03-01

    Biochemical data and skeletal histomorphometric measurements are presented for normal rats and for two groups of rats rendered uremic by partial nephrectomy. In one of these groups chronic acidosis was induced by the oral administration of hydrochloric acid. Uremic animals had higher urine calcium excretion rates and lower serum concentrations of vitamin D metabolites than normal rats. Chronic acid loading of uremic rats resulted in hypercalcemia, elevated serum parathyroid hormone concentrations, and a significant loss of trabecular bone in addition to the above changes. greater osteoclast densities and higher resorption surfaces wee seen in the uremic acidotic animals than in the other two groups. The acidotic uremic state induced more potent changes in calcium metabolism and bone structure than uremia alone. PMID:3924372

  10. The status of Vitamin D in medical students in the preclerkship years of a Saudi medical school

    PubMed Central

    Al-Elq, Abdulmohsen H.

    2012-01-01

    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

  11. Prevalence of hypovitaminosis D and predictors of vitamin D status in Italian healthy adolescents

    PubMed Central

    2014-01-01

    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

  12. Primary hyperparathyroidism and metabolic risk factors, impact of parathyroidectomy and vitamin D supplementation, and results of a randomized double-blind study

    PubMed Central

    Norenstedt, Sophie; Pernow, Ylva; Brismar, Kerstin; Sääf, Maria; Ekip, Ayla; Granath, Fredrik; Zedenius, Jan; Nilsson, Inga-Lena

    2013-01-01

    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

  13. Identification and preservation of the parathyroid gland during total thyroidectomy in dogs with bilateral thyroid carcinoma: a report of six cases

    PubMed Central

    FUKUI, Sho; ENDO, Yoshifumi; HIRAYAMA, Kazuko; TANIYAMA, Hiroyuki; KADOSAWA, Tsuyoshi

    2015-01-01

    Simultaneous removal of bilateral thyroid tumors was performed while preserving the parathyroid gland in six dogs. At least one external parathyroid gland was identified in all dogs. In five cases, the external parathyroid gland and its blood supply were preserved intact. In one dog, the vessels supplying the external parathyroid gland had been invaded by the tumor, and the gland was thus removed and reimplanted into the sternohyoid muscle. That dog required postoperative treatment with oral calcium gluconate and vitamin D3. Local tumor recurrence was not observed in any of the cases. The mean survival time was 920 days. We found that the external parathyroid gland could be identified and preserved in most dogs undergoing total thyroidectomy. PMID:25716481

  14. Identification and preservation of the parathyroid gland during total thyroidectomy in dogs with bilateral thyroid carcinoma: a report of six cases.

    PubMed

    Fukui, Sho; Endo, Yoshifumi; Hirayama, Kazuko; Taniyama, Hiroyuki; Kadosawa, Tsuyoshi

    2015-07-01

    Simultaneous removal of bilateral thyroid tumors was performed while preserving the parathyroid gland in six dogs. At least one external parathyroid gland was identified in all dogs. In five cases, the external parathyroid gland and its blood supply were preserved intact. In one dog, the vessels supplying the external parathyroid gland had been invaded by the tumor, and the gland was thus removed and reimplanted into the sternohyoid muscle. That dog required postoperative treatment with oral calcium gluconate and vitamin D3. Local tumor recurrence was not observed in any of the cases. The mean survival time was 920 days. We found that the external parathyroid gland could be identified and preserved in most dogs undergoing total thyroidectomy. PMID:25716481

  15. Bone marrow levels of 25 hydroxy vitamin D are not depressed in cases of hip fracture compared with controls.

    PubMed

    Power, J; Taggart, J; Parker, M; Berry, J L; Reeve, J

    2014-06-01

    There is little information on tissue as distinct from plasma levels of vitamin D metabolites in cases of hip fracture compared with controls. Femoral neck fractures in the elderly are associated with increased cortical remodelling and endosteal resorption, leading to regional increases in porosity and reduced cortical thickness. Vitamin D metabolites play a central role in the maintenance of normal serum calcium levels and may, through interactions with parathyroid hormone, exert an important influence on bone structure. To investigate whether hip fracture might be associated with tissue vitamin D deficiency, we have measured by radioimmunoassay the levels of 25 hydroxy vitamin D (25 (OH)D) in bone marrow samples extracted from the proximal femurs of 16 female subjects who had suffered fracture (mean age?=?82.1?years, standard error (se) 1.9) and nine sex matched post mortem controls (mean age?=?83.8?years, se 2.5). Twenty five (OH)D concentrations were significantly greater in the fracture cases (median?=?3.7, IQR?=?2.5-3.9?ng/g) than in the control group (median?=?1.5, IQR?=?0.9-2.3?ng/g; P?=?0.0007, non-parametric Wilcoxon/Kruskal-Wallis test). It was suggested in the 1970s that bone loss and hip fracture risk in the UK were driven by vitamin D deficiency. Our results suggest that the alterations in femoral neck bone microstructure and remodelling in hip fracture cannot be assigned to the single cause of relative deficiency of vitamin D. Vitamin D deficiency or insufficiency may nevertheless increase remodelling and loss of bone tissue and contribute causally to a minority of hip fractures. PMID:24375617

  16. A case of low bone mineral density with vitamin d deficiency due to prolonged lactation and severe malnutrition.

    PubMed

    Shin, Min Young; Kang, Yea Eun; Kong, Si Eun; Ju, Sang Hyeon; Back, Min Kyung; Kim, Koon Soon

    2015-02-01

    Malnutrition associated vitamin D deficiency contributes to the calcium loss from bone and results in osteoporosis and osteomalacia at final stage. Osteomalacia is characterized with softening of bone secondary to defective bone mineralization. Here, we report a case of possible osteomalacia caused by prolonged lactation and severe malnutrition in 35-year-old female. She was a housewife and her body mass index was 11.8 kg/m(2). She was diagnosed with severe osteoporosis in regular health check-up 2 years ago, but did not take any medication. Nine months ago, she had been treated with anti-tuberculosis medications for 6 month due to active pulmonary tuberculosis. After complete remission of pulmonary tuberculosis, she had lost her appetite severely. Furthermore, she felt gait difficulty and suffered from generalized bone pain. On serologic examination, hypocalcemia, hypophosphatemia, high alkaline phosphatase, low vitamin D3 and high parathyroid hormone level were seen. In the bone mineral density, Z-score from her lumbar spine was -6.5. She was treated with oral calcium and vitamin D3 intramuscularly. After 1 year treatment, she felt significant improvement in bone pain and could walk alone. Also her serum calcium, phosphate and vitamin D3 level are all normalized. PMID:25774364

  17. Increase in the dosage amount of vitamin D3 preparations by switching from calcium carbonate to lanthanum carbonate.

    PubMed

    Hyodo, Toru; Kawakami, Junko; Mikami, Noriko; Wakai, Haruki; Ishii, Daisuke; Yoshida, Kazunari; Iwamura, Masatsugu; Hida, Miho; Kurata, Yasuhisa

    2014-06-01

    It is widely known that dialysis patients who are administered vitamin D preparations have a better prognosis than patients who are not. In this study, of 22 patients on maintenance dialysis who had been administered calcium (Ca) carbonate in our hospital, we investigated the dosage amount of vitamin D3 preparations after the phosphorus (P) binder was switched from Ca carbonate to the newly developed lanthanum carbonate (LC). After completely switching to LC, the dosage amount of oral vitamin D3 preparation (alfacalcidol equivalent) was significantly increased from 0.094 ?g/day to 0.375 ?g/day (P = 0.0090). No significant changes were observed in the values of serum corrected Ca, alkaline phosphatase, intact parathyroid hormone and P after switching. The administration of LC enabled complete cessation of the administration of Ca carbonate preparations, and increased the dosage amount of vitamin D3 preparations. Therefore, LC may be a useful P binder to improve patient prognosis. PMID:24953761

  18. Parathyroid autotransplantation in extensive head and neck resections: case series report

    PubMed Central

    2011-01-01

    Permanent or temporary hypoparathyroidism may be a debilitating result of radical cervical surgery, as noted most commonly following thyroid or parathyroid surgery. However, it can also be the outcome of any surgical procedure involving bilateral extensive manipulation of the anterior neck triangle, especially in order to ensure oncologically adequate surgical margins. We report our experience of three patients that underwent parathyroid immediate autotransplanation following extensive surgical manipulations of the neck region for oncological reasons. PTH levels were restored to normal by the fourth postoperative week, allowing us to wean the patients off calcium and vitamin D3 supplementation, which was attributed to full autograft function. Parathyroid autotransplantation, immediate or delayed, is a simple and safe technique which should be considered by the surgeon whenever there is a high risk for postoperative hypoparathyroidism following radical operations of the neck for oncological reasons. PMID:22085420

  19. Transoral thyroid and parathyroid surgery

    Microsoft Academic Search

    Elias Karakas; Thorsten Steinfeldt; Andreas Gockel; Reiner Westermann; Anja Kiefer; Detlef K. Bartsch

    2010-01-01

    Background  Translumenal endoscopic interventions via so-called natural orifices are gaining increasing interest because they allow surgical\\u000a treatment without any incision of the skin. Moreover, minimally invasive procedures have found their way into thyroid and\\u000a parathyroid surgery. Our goal was to develop a new access for thyroid and parathyroid resection via an entirely transoral\\u000a approach.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  We managed to find an entirely transoral

  20. Parathyroid storm: immediate recognition and pathophysiological considerations.

    PubMed

    Minisola, S; Romagnoli, E; Scarnecchia, L; Pacitti, M T; Rosso, R; Carnevale, V; Minisola, G; Mazzuoli, G

    1993-01-01

    A 56-year-old white man was referred for evaluation of severe hypercalcemia following a three-week history of progressive weakness, nausea, and depression. Initial laboratory results showed serum total and ionized calcium (Ca++) values of 5.3 and 2.6 mmol/l, respectively. A short intact PTH assay was immediately performed and an extremely high value was obtained in just 30 min (1315 ng/l, normal values 6.4-70.4). The patient was therefore treated with saline solution and with salmon calcitonin (1200 IU/day, half by continuous i.v. infusion and half by i.m. route) for 10 days. There was a sudden decrease of both Ca++ and intact PTH during the first six days; then there was a trend to reach a steady-state until parathyroidectomy was performed. After withdrawal of calcitonin therapy it was possible to observe a positive uncoupling between bone formation (serum alkaline phosphatase and osteocalcin) and resorption (serum tartrate-resistant acid phosphatase) markers. On day 35 the patient underwent neck exploration, and an enlarged lower left parathyroid gland was removed that on macroscopic examination revealed the presence of a haemorrhagic cyst; microscopic appearance was suggestive of a previous glandular infarction. This is the first time the daily clinical course of a parathyroid crisis has been documented. Furthermore, changes of biomarkers of bone turnover following calcitonin therapy show that high doses of the hormone may cause a prolonged positive uncoupling of the two processes of bone remodeling. PMID:8268042

  1. Dissecting high from low responders in a vitamin D3 intervention study.

    PubMed

    Saksa, Noora; Neme, Antonio; Ryynänen, Jussi; Uusitupa, Matti; de Mello, Vanessa D F; Voutilainen, Sari; Nurmi, Tarja; Virtanen, Jyrki K; Tuomainen, Tomi-Pekka; Carlberg, Carsten

    2015-04-01

    Vitamin D3 is a pleiotropic signaling molecule that has via activation of the transcription factor vitamin D receptor (VDR) a direct effect on the expression of more than 100 genes. The aim of this study was to find transcriptomic and clinical biomarkers that are most suited to identify vitamin D3 responders within 71 pre-diabetic subjects during a 5-month intervention study (VitDmet). In hematopoietic cells, the genes ASAP2, CAMP, CD14, CD97, DUSP10, G0S2, IL8, LRRC8A, NINJ1, NRIP1, SLC37A2 and THBD are known as primary vitamin D targets. We demonstrate that each of these 12 genes carries a conserved VDR binding site within its genomic region and is expressed in human peripheral blood mononuclear cells (PBMCs). The changes in the expression of these genes in human PBMCs at the start and the end of the vitamin D-intervention were systematically correlated with the alteration in the circulating form of vitamin D3, 25-hydroxyvitamin D3 (25(OH)D3). Only 39-44 (55-62%) of the study subjects showed a highly significant response to vitamin D3, i.e., we considered them as "responders". In comparison, we found for 37-53 (52-75%) of the participants that only 12 biochemical and clinical parameters, such as concentrations of parathyroid hormone (PTH) and insulin, or computed values, such as homeostatic model assessment and insulin sensitivity index, show a correlation with serum 25(OH)D3 levels that is as high as that of the selected VDR target genes. All 24 parameters together described the pleiotropic vitamin D response of the VitDmet study subjects. Interestingly, they demonstrated a number of additional correlations that define a network, in which PTH plays the central role. In conclusion, vitamin D3-induced changes in human PBMCs can be described by transcriptomic and serum biomarkers and allow a segregation into high and low responders. This article is part of a Special Issue entitled '17th Vitamin D Workshop' . PMID:25448738

  2. Vitamin E

    MedlinePLUS

    ... Consumer Datos en espańol Health Professional Other Resources Vitamin E Fact Sheet for Consumers What is vitamin E and what does it do? Vitamin E ... out more about vitamin E? Disclaimer How much vitamin E do I need? The amount of vitamin ...

  3. A large intrathoracic parathyroid adenoma.

    PubMed Central

    Daggett, P; Johnston, I D; Lowe, D

    1976-01-01

    A case is described in which an unusually large parathyroid adenoma was visible on the plain chest radiograph taken during the investigation of hypercalcaemia. This was diagnosed preoperatively and a scheme is suggested whereby such a disgnosis can now readily be made. The differential diagnosis is discussed ant the literature is reviewed. Images PMID:1013950

  4. A role for magnesium in neonatal parathyroid gland function

    SciTech Connect

    Loughead, J.L.; Mimouni, F.; Tsang, R.C.; Khoury, J.C. (Univ. of Cincinnati College of Medicine, OH (USA))

    1991-04-01

    Little is known of the factors regulating parathyroid function in the neonatal period. Twenty-seven term infants born after uncomplicated pregnancies, labors, and deliveries were studied to test the hypothesis that in normal newborns the amplitude of parathyroid hormone (PTH) response to decreasing serum ionized calcium (iCa) correlates with serum magnesium (Mg) concentrations. Serum iCa (ion selective electrode, Radiometer ICA 1), PTH (1-84 intact molecules, radioimmunoassay) and Mg (atomic absorption) were measured at birth (cord blood) and 24 hours of age. Repeated measures analysis of covariance showed decreasing serum iCa (p less than 0.01) and increasing serum Mg (p less than 0.01) and PTH (p less than 0.01) over time. The change in PTH over the first 24 hours was directly correlated with cord blood (r = 0.38, p less than 0.05) and 24-hr Mg concentrations (r = 0.53, p less than 0.01). We conclude that the ability of the parathyroid gland to respond to decreasing serum iCa after birth is directly related to Mg status. We speculate that neonatal hypomagnesemia may lead to a blunted PTH secretory response, thus contributing to early neonatal hypocalcemia.

  5. Increased anxiety in mice lacking vitamin D receptor gene

    E-print Network

    Kalueff, Allan V.

    Increased anxiety in mice lacking vitamin D receptor gene Allan V. Kalueˇ,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

  6. 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

    2013-01-01

    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. PMID:24041337

  7. Vitamin D receptors in breast cancer cells

    Microsoft Academic Search

    Robert R. Buras; Lisa M. Schumaker; Fatemeh Davoodi; Richard V. Brenner; Mohsen Shabahang; Russell J. Nauta; Stephen R. T. Evans

    1994-01-01

    1,25-(OH)2-Vitamin D3, the active metabolite of vitamin D, is a secosteroid hormone with known differentiating activity in leukemic cells. Studies have demonstrated the presence of vitamin D receptors (VDR) in a wide range of tissues and cell types. Antiproliferative activity of 1,25-(OH)2-vitamin D3 has been documented in osteosarcoma, melanoma, colon carcinoma, and breast carcinoma cells. This study was designed to

  8. An Unusual Neck Mass: A Case of a Parathyroid Cyst and Review of the Literature

    PubMed Central

    Goomany, Anand; Rafferty, Amy; Smith, Ian

    2015-01-01

    Parathyroid cysts (PC) are an unusual cause of neck swellings. The majority are nonfunctioning and prove to be a diagnostic challenge given their nonspecific physical and radiological characteristics. This is compounded by their rare occurrence, leading them to be overlooked in the differential diagnosis of neck lumps. Imaging techniques fail to determine the origin of these lesions, but a preoperative diagnosis can be achieved by fine-needle aspiration and measurement of cystic fluid C-terminal parathyroid hormone levels. Treatment of nonfunctioning cysts remains controversial and includes needle aspiration, injection of sclerosant, or surgical excision. We present a case of a 44-year-old female presenting with an asymptomatic anterior neck swelling, diagnosed postoperatively as a parathyroid cyst.

  9. Phosphatonins: new hormones involved in numerous inherited bone disorders

    PubMed Central

    Masi, Laura

    2011-01-01

    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

  10. Maternal Vitamin D Status and Its Related Factors in Pregnant Women in Bangkok, Thailand

    PubMed Central

    Pratumvinit, Busadee; Wongkrajang, Preechaya; Wataganara, Tuangsit; Hanyongyuth, Sithikan; Nimmannit, Akarin; Chatsiricharoenkul, Somruedee; Manonukul, Kotchamol; Reesukumal, Kanit

    2015-01-01

    Background There are few data focusing on the prevalence of vitamin D deficiency in tropical countries. Objectives We determined the vitamin D status in pregnant women and examined the factors associated with vitamin D deficiency. Design and Methods A cross-sectional study of 147 pregnant Thai women aged 18–45 years at Siriraj Hospital (a university hospital in Bangkok, Thailand) was undertaken. Clinical data and plasma levels of 25-hydroxyvitamin D [25(OH)D], intact parathyroid hormone (iPTH), calcium, albumin, phosphate and magnesium were obtained in pregnant women at delivery. Results The prevalence of hypovitaminosis D [defined as 25(OH)D <75 nmol/L] in pregnant women at delivery was 75.5% (95% confidence interval (CI), 67.7–82.2%). Of these, vitamin D insufficiency [defined as 25(OH)D 50–74.9 nmol/L] was found in 41.5% (95% CI, 33.4–49.9%) and vitamin D deficiency [25(OH)D <50 nmol/L] was found in 34.0% (95% CI, 26.4–42.3%) of women. The mean 25(OH)D concentration was 61.6±19.3 nmol/L. The correlation between 25(OH)D and iPTH was weak (r = –0.29, P<0.01). Factors associated with vitamin D deficiency by multiple logistic regression were: pre-pregnancy body mass index (BMI in kg/m2, odds ratio (OR), 0.88, 95% CI 0.80–0.97, P = 0.01) and season of blood collection (winter vs. rainy, OR, 2.62, 95% CI 1.18–5.85, P = 0.02). Conclusions Vitamin D deficiency is common among pregnant Thai women. The prevalence of vitamin D deficiency increased in women who had a lower pre-pregnancy BMI and whose blood was collected in the winter. Vitamin D supplementation may need to be implemented as routine antenatal care. PMID:26147381

  11. Association between serum level of vitamin D and lipid profiles in type 2 diabetic patients in Iran

    PubMed Central

    2014-01-01

    Background It is suggested that vitamin D deficiency is associated with cardiovascular disease (CVD) via its effect on lipid profiles. The objective of this study was to determine the association between fasting serum levels of 25(OH) D and lipid profiles in patients with type 2 diabetes. Methods This cross-sectional study was conducted on 108 type 2 diabetics. Patients were selected randomly among members of the Iranian Diabetes Association according to study criteria. Fasting concentration of 25(OH) D, calcium, phosphorus, parathyroid hormone (PTH) and lipid profiles (including triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol) were measured. Results The mean serum levels of 25-hydroxyvitamin D (25(OH) D) and PTH were 53.41?±?33.25 nmol/l and 40.24?±?18.24 pmol/l, respectively, in type 2 diabetic patients. Prevalence of vitamin D deficiency was 58.34% and vitamin D sufficiency and insufficiency combined was 41.66%. Although in diabetic patients with vitamin D deficiency, serum levels of total cholesterol, TG, and LDL were higher and HDL was lower compared to patients with vitamin D sufficiency, this association was statistically significant only for serum level of TG (145.91?±?79.00 vs. 122.95?±?55.82 mg/dl). Conclusions The results of present study show that serum concentrations of 25(OH) D were inversely associated with TG. More interventional studies are needed to confirm the relationship between serum concentration of vitamin D and lipid profile in patients with type 2 diabetes. PMID:24398023

  12. Vitamin D receptor agonists increase klotho and osteopontin while decreasing aortic calcification in mice with chronic kidney disease fed a high phosphate diet.

    PubMed

    Lau, Wei Ling; Leaf, Elizabeth M; Hu, Ming Chang; Takeno, Marc M; Kuro-o, Makoto; Moe, Orson W; Giachelli, Cecilia M

    2012-12-01

    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 3 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 anticalcification 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

  13. Activation of calcium-sensing receptor accelerates apoptosis in hyperplastic parathyroid cells

    SciTech Connect

    Mizobuchi, Masahide [Department of Nephrology, School of Medicine, Showa University, Tokyo (Japan); Ogata, Hiroaki [Department of Internal Medicine, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-chuo, Tsuzuki, Yokohama 224-8503 (Japan)], E-mail: ogatah@med.showa-u.ac.jp; Hatamura, Ikuji [First Department of Pathology, Wakayama Medical University, Wakayama (Japan); Saji, Fumie [Division of Nephrology and Blood Purification Medicine, Wakayama Medical University, Wakayama (Japan); Koiwa, Fumihiko [Division of Nephrology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama (Japan); Kinugasa, Eriko [Department of Internal Medicine, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-chuo, Tsuzuki, Yokohama 224-8503 (Japan); Koshikawa, Shozo [Division of Nephrology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama (Japan); Akizawa, Tadao [Department of Nephrology, School of Medicine, Showa University, Tokyo (Japan)

    2007-10-12

    Calcimimetic compounds inhibit not only parathyroid hormone (PTH) synthesis and secretion, but also parathyroid cell proliferation. The aim of this investigation is to examine the effect of the calcimimetic compound NPS R-568 (R-568) on parathyroid cell death in uremic rats. Hyperplastic parathyroid glands were obtained from uremic rats (subtotal nephrectomy and high-phosphorus diet), and incubated in the media only or the media which contained high concentration of R-568 (10{sup -4} M), or 10% cyclodextrin, for 6 h. R-568 treatment significantly suppressed medium PTH concentration compared with that of the other two groups. R-568 treatment not only increased the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay-positive cells, but also induced the morphologic changes of cell death determined by light or electron microscopy. These results suggest that CaR activation by R-568 accelerates parathyroid cell death, probably through an apoptotic mechanism in uremic rats in vitro.

  14. Vitamin A

    MedlinePLUS

    ... Datos en espańol Health Professional Other Resources Vitamin A Fact Sheet for Consumers What is vitamin A and what does it do? Vitamin A is ... dietary supplements is beta-carotene . How much vitamin A do I need? The amount of vitamin A ...

  15. Effect of adiposity, season, diet and calcium or vitamin D supplementation on the vitamin D status of healthy urban African and Asian-Indian adults.

    PubMed

    George, Jaya A; Norris, Shane A; van Deventer, Hendrick E; Pettifor, John M; Crowther, Nigel J

    2014-08-28

    Vitamin D deficiency has been implicated in the aetiology of infectious diseases and metabolic syndrome. These diseases are prevalent in the African and Asian-Indian populations of South Africa; however, there is limited data on 25-hydroxyvitamin D (25(OH)D) concentrations in these populations. The aim of the present study was to assess the vitamin D status and its predictors in healthy adults in Johannesburg. We assessed the vitamin D status of 730 adult African and Asian-Indian subjects residing in Johannesburg. The contributions of sun exposure, season, dietary intake of Ca and vitamin D, total body fat and body fat distribution to 25(OH)D concentrations were assessed. The concentrations of 25(OH)D were measured by HPLC. The contribution of 25(OH)D? to total 25(OH)D concentrations was assessed. The mean age of the subjects was 42·6 (SD 13·1) years (range: 18-65). Concentrations of 25(OH)D < 30 nmol/l were found in 28·6 % of the Asian-Indian subjects in comparison with 5·1 % of the African subjects (P< 0·0001). Parathyroid hormone (PTH) concentrations were negatively associated with 25(OH)D concentrations, while season and sun exposure were positive predictors explaining 16 % of the variance in 25(OH)D concentrations (P< 0·0001) in the African subjects. In the Asian-Indian subjects, PTH concentrations were negatively associated with 25(OH)D concentrations, while male sex, season and Ca supplementation were positive predictors and explained 17 % of the variance in 25(OH)D concentrations (P< 0·0001). In the multivariate regression analysis, neither total body fat nor body fat distribution was predictive of 25(OH)D concentrations in either group. In conclusion, factors such as sun exposure, dietary supplement use and ethnicity are important determinants of plasma 25(OH)D concentrations. PMID:24877635

  16. Placental vitamin D receptor (VDR) expression is related to neonatal vitamin D status, placental calcium transfer, and fetal bone length in pregnant adolescents.

    PubMed

    Young, Bridget E; Cooper, Elizabeth M; McIntyre, Allison W; Kent, Tera; Witter, Frank; Harris, Z Leah; O'Brien, Kimberly O

    2014-05-01

    The purpose of the study was to identify determinants of placental vitamin D receptor (VDR) expression and placental calcium (Ca) transfer among pregnant adolescents. Placental tissue was obtained in 94 adolescents (?18 yr) at term. In 12 of these teens, stable Ca isotopes were given intravenously ((42)Ca) and orally ((44)Ca) early in labor. Placental VDR expression was assessed via Western blot and validated by RT-PCR. Maternal-to-fetal Ca transfer was calculated as the enrichment in cord blood at delivery relative to maternal serum enrichment 2 h postdosing. Isotopic study outcomes were examined in relation to fetal long bone length, placental VDR, serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], and parathyroid hormone (PTH) in maternal circulation and cord blood at delivery. Placental VDR expression was inversely associated with neonatal 25(OH)D (P=0.012) and positively with neonatal 1,25(OH)2D (P=0.006). Placental VDR was a positive predictor of fetal femur length Z score (P=0.018; R(2)=0.06) and was positively correlated with maternal-to-fetal transfer of intravenous (42)Ca (P=0.004; R(2)=0.62). The fetus may regulate placental VDR expression given the significant associations with neonatal vitamin D metabolites. The association between placental VDR and fetal long bone length may indicate a role for VDR in fetal bone development, potentially by mediating transplacental Ca transfer. PMID:24558197

  17. Vitamin D in Thyroid Disorders.

    PubMed

    Kmie?, P; Sworczak, K

    2015-07-01

    Vitamin D's canonical role are its effects exerted on the musculoskeletal system. In the last decades the importance of this hormone has been studied in the context of extraskeletal health. Hypovitaminosis D and several polymorphic variants of genes coding proteins crucial in the transport, metabolism and effects of vitamin D have been associated with negative health outcomes.In this review the current state of knowledge on the role of vitamin D in thyroid disorders is presented. The review is based on a literature search of the PubMed database performed in December 2014. The following search terms were used in conjunction with 'vitamin D': thyroid cancer, Graves', Hashimoto, thyroiditis, autoimmune thyroid, AITD, nodules, hyperthyroidism, and hypothyroidism.Currently, similarly to other extraskeletal health outcomes, a clear role of vitamin D has not been demonstrated in thyroid disorders. Further research is necessary to fully elucidate the importance of vitamin D in case of thyroid disease. PMID:26171622

  18. Vitamin D-Binding Protein Influences Total Circulating Levels of 1,25-Dihydroxyvitamin D3 but Does Not Directly Modulate the Bioactive Levels of the Hormone in Vivo

    PubMed Central

    Zella, Lee A.; Shevde, Nirupama K.; Hollis, Bruce W.; Cooke, Nancy E.; Pike, J. Wesley

    2008-01-01

    Mice deficient in the expression of vitamin D-binding protein (DBP) are normocalcemic despite undetectable levels of circulating 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. We used this in vivo mouse model together with cells in culture to explore the impact of DBP on the biological activity of 1,25(OH)2D3. Modest changes in the basal expression of genes involved in 1,25(OH)2D3 metabolism and calcium homeostasis were observed in vivo; however, these changes seemed unlikely to explain the normal calcium balance seen in DBP-null mice. Further investigation revealed that despite the reduced blood levels of 1,25(OH)2D3 in these mice, tissue concentrations were equivalent to those measured in wild-type counterparts. Thus, the presence of DBP has limited impact on the extracellular pool of 1,25(OH)2D3 that is biologically active and that accumulates within target tissues. In cell culture, in contrast, the biological activity of 1,25(OH)2D3 is significantly impacted by DBP. Here, although DBP deficiency had no effect on the activation profile itself, the absence of DBP strongly reduced the concentration of exogenous 1,25(OH)2D3 necessary for transactivation. Surprisingly, analogous studies in wild-type and DBP-null mice, wherein we explored the activity of exogenous 1,25(OH)2D3, produced strikingly different results as compared with those in vitro. Here, the carrier protein had virtually no impact on the distribution, uptake, activation profile, or biological potency of the hormone. Collectively, these experiments suggest that whereas DBP is important to total circulating 1,25(OH)2D3 and sequesters extracellular levels of this hormone both in vivo and in vitro, the binding protein does not influence the hormone’s biologically active pool. PMID:18372326

  19. Differentiated tonsil-derived mesenchymal stem cells embedded in Matrigel restore parathyroid cell functions in rats with parathyroidectomy.

    PubMed

    Park, Yoon Shin; Kim, Han Su; Jin, Yoon Mi; Yu, Yeonsil; Kim, Ha Yeong; Park, Hae Sang; Jung, Sung-Chul; Han, Ki-Hwan; Park, Yoon Jeong; Ryu, Kyung-Ha; Jo, Inho

    2015-10-01

    Parathyroid cells release parathyroid hormone (PTH), which controls calcium homeostasis. Loss of parathyroid cells results in hypoparathyroidism and consequent low-turnover bone disease. Here, we investigated whether our recently-established human tonsil-derived mesenchymal stem cells (TMSC) restore in vivo parathyroid cell function in rats with parathyroidectomy (PTX). Compared with undifferentiated control TMSC, TMSC differentiated with activin A and soluble sonic hedgehog induced a significant release of PTH as early as day 7, with increased PTH release occurring in response to lower calcium levels and vice versa. Released PTH increased osteocalcin expression and alizarin red S staining in preosteoblastic cells, indicating its functional activity. PTX rats fed calcium-free diet only survived for ?10 days. Subcutaneous injection with TMSC alone did not increase their survival rates, regardless of differentiation. However, survival rates increased for up to 28 days in response to TMSC embedded in Matrigel (TMSC-MA), showing 40% and 80% in control and differentiated TMSC-MA, respectively. When compared with continuous increases by control TMSC-MA, stable levels of secreted PTH and serum ionized calcium were found in PTX rats with differentiated TMSC-MA. This is the first report that differentiated TMSC resemble parathyroid cells and, if embedded in Matrigel, restore in vivo parathyroid function. PMID:26156233

  20. Transcriptional Repression of the Interleukin2 Gene by Vitamin D 3 : Direct Inhibition of NFATp\\/AP1 Complex Formation by a Nuclear Hormone Receptor

    Microsoft Academic Search

    IRIS ALROY; TERRI L. TOWERS; ANDLEONARD P. FREEDMAN

    1995-01-01

    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

  1. Relation of body fat indexes to vitamin D status and deficiency among obese adolescents1234

    PubMed Central

    Feldman, Henry A; Von Scheven, Emily; Merewood, Anne; Sweeney, Carol; Wilson, Darrell M; Lee, Phillip DK; Abrams, Stephanie H; Gitelman, Stephen E; Wertz, Marcia S; Klish, William J; Taylor, George A; Chen, Tai C; Holick, Michael F

    2009-01-01

    Background: Data on the relation between vitamin D status and body fat indexes in adolescence are lacking. Objective: The objective was to identify factors associated with vitamin D status and deficiency in obese adolescents to further evaluate the relation of body fat indexes to vitamin D status and deficiency. Design: Data from 58 obese adolescents were obtained. Visceral adipose tissue (VAT) was measured by computed tomography. Dual-energy X-ray absorptiometry was used to measure total bone mineral content, bone mineral density, body fat mass (FM), and lean mass. Relative measures of body fat were calculated. Blood tests included measurements of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), osteocalcin, type I collagen C-telopeptide, hormones, and metabolic factors. Vitamin D deficiency was defined as 25(OH)D < 20 ng/mL. PTH elevation was defined as PTH > 65 ng/mL. Results: The mean (±SD) age of the adolescents was 14.9 ± 1.4 y; 38 (66%) were female, and 8 (14%) were black. The mean (±SD) body mass index (in kg/m2) was 36 ± 5, FM was 40.0 ± 5.5%, and VAT was 12.4 ± 4.3%. Seventeen of the adolescents were vitamin D deficient, but none had elevated PTH concentrations. Bone mineral content and bone mineral density were within 2 SDs of national standards. In a multivariate analysis, 25(OH)D decreased by 0.46 ± 0.22 ng/mL per 1% increment in FM (? ± SE, P = 0.05), whereas PTH decreased by 0.78 ± 0.29 pg/mL per 1% increment in VAT (P = 0.01). Conclusions: To the best of our knowledge, our results show for the first time that obese adolescents with 25(OH)D deficiency, but without elevated PTH concentrations, have a bone mass within the range of national standards (±2 SD). The findings provide initial evidence that the distribution of fat may be associated with vitamin D status, but this relation may be dependent on metabolic factors. This study was registered at www.clinicaltrials.gov as NCT00209482, NCT00120146. PMID:19640956

  2. 2-Methoxyisobutylisonitrile Probe during Parathyroid Surgery: Tool or Gadget?

    Microsoft Academic Search

    H. Jaap Bonjer; Hajo A. Bruining; Huib A. P. Pols; Wouter W. de Herder; Charles A. G. Proye; Bruno M. L. Carnaille; Robert S. A. Mohammedamin; Ewout W. Steyerberg; Wout A. P. Breeman; Erik P. Krenning

    1998-01-01

    . The success of parathyroid surgery is determined by the identification and removal of all parathyroid tumors. Parathyroid\\u000a tumors accumulate and retain 2-methoxyisobutylisonitrile (MIBI) labeled with technetium-99m. Intravenous injection of this\\u000a radiopharmacon prior to parathyroid surgery allows identification of parathyroid tumors with a hand-held gamma detector. To\\u000a assess the value of this technique, a case–control study was performed with 62

  3. Parathyroid adenoma apoplexy as a temporary solution of primary hyperparathyroidism: a case report

    PubMed Central

    Pereira, Francisco A; Brandăo, Daniel F; Elias, Jorge; Paula, Francisco JA

    2007-01-01

    Introduction The natural history of patients with spontaneous parathyroid necrosis is unknown. In this case report we describe the clinical course, laboratory, radiographic, bone densitometry tests, parathyroid ultrasonography and scintigraphy examinations of a patient performed over a period of eight years after she first presented with a sudden episode of spontaneous resolution of primary hyperparathyroidism (PHPT). Case presentation A 24-year-old woman with a clinical history and laboratory and radiographic tests compatible with PHPT suffered a sudden episode of cervical pain and presented with clinical evidence of hypocalcemia. Biopsy of a cervical nodule revealed necrotic material compatible with ischemia of the parathyroid. The follow-up of the patient presented four distinct phases: the first, which lasted two years, was compatible with a period of bone hunger during which it was necessary to introduce calcitriol and calcium carbonate. During this period, the patient showed bone mass gain. The second phase was characterized by normalization of calcium and parathyroid hormone levels and its end was difficult to define. During the third phase there was a recurrence of hypercalcemia associated with elevated parathyroid hormone (PTH) levels and loss of bone mass. The last phase corresponded to the interval after parathyroidectomy, which was characterized by normalization of serum levels of calcium and PTH, as well as bone mass gain. Conclusion This case report indicates that spontaneous resolution of PHPT by adenoma necrosis is potentially temporary. Thus, in cases in which a conservative approach is chosen, clinical and laboratory follow-up is indispensable. Bone mass measurement is a useful tool in the follow-up of these cases. However, this option exposes the patient to a potential roller-coaster ride of bone mass gain and loss, whose long term consequences are still unknown. PMID:18021421

  4. Vitamin D Deficiency

    PubMed Central

    Alshishtawy, Moeness Moustafa

    2012-01-01

    Recently, scientists have generated a strong body of evidence providing new information about the preventive effect of vitamin D on a broad range of disorders. This evidence suggests that vitamin D is much more than a nutrient needed for bone health; it is an essential hormone required for regulation of a large number of physiological functions. Sufficient concentration of serum 25-hydroxyvitamin D is essential for optimising human health. This article reviews the present state-of-the-art knowledge about vitamin D’s status worldwide and refers to recent articles discussing some of the general background of vitamin D, including sources, benefits, deficiencies, and dietary requirements, especially in pregnancy. They offer evidence that vitamin D deficiency could be a major public health burden in many parts of the world, mostly because of sun deprivation. The article also discusses the debate about optimal concentration of circulating serum 25-hydroxyvitamin D, and explores different views on the amount of vitamin D supplementation required to achieve and maintain this concentration. PMID:22548132

  5. Vitamin neurotoxicity.

    PubMed

    Snodgrass, S R

    1992-01-01

    Vitamins contain reactive functional groups necessary to their established roles as coenzymes and reducing agents. Their reactive potential may produce injury if vitamin concentration, distribution, or metabolism is altered. However, identification of vitamin toxicity has been difficult. The only well-established human vitamin neurotoxic effects are those due to hypervitaminosis A (pseudotumor cerebri) and pyridoxine (sensory neuropathy). In each case, the neurological effects of vitamin deficiency and vitamin excess are similar. Closely related to the neurological symptoms of hypervitaminosis A are symptoms including headache, pseudotumor cerebri, and embryotoxic effects reported in patients given vitamin A analogs or retinoids. Most tissues contain retinoic acid (RA) and vitamin D receptors, members of a steroid receptor superfamily known to regulate development and gene expression. Vitamin D3 effects on central nervous system (CNS) gene expression are predictable, in addition to the indirect effects owing to its influence on calcium and phosphorus homeostasis. Folates and thiamine cause seizures and excitation when administered in high dosage directly into the brain or cerebrospinal fluid (CSF) of experimental animals but have rarely been reported to cause human neurotoxicity, although fatal reactions to i.v. thiamine are well known. Ascorbic acid influences CNS function after peripheral administration and influences brain cell differentiation and 2-deoxyglucose accumulation by cultured glial cells. Biotin influences gene expression in animals that are not vitamin-deficient and alters astrocyte glucose utilization. The multiple enzymes and binding proteins involved in regeneration of retinal vitamin A illustrate the complexity of vitamin processing in the body. Vitamin A toxicity is also a good general model of vitamin neurotoxicity, because it shows the importance of the ratio of vitamin and vitamin-binding proteins in producing vitamin toxicity and of CNS permeability barriers. Because vitamin A and analogs enter the CNS better than most vitamins, and because retinoids have many effects on enzyme activity and gene expression, Vitamin A neurotoxicity is more likely than that of most, perhaps all other vitamins. Megadose vitamin therapy may cause injury that is confused with disease symptoms. High vitamin intake is more hazardous to peripheral organs than to the nervous system, because CNS vitamin entry is restricted. Vitamin administration into the brain or CSF, recommended in certain disease states, is hazardous and best avoided. The lack of controlled trials prevents us from defining the lowest human neurotoxic dose of any vitamin. Large differences in individual susceptibility to vitamin neurotoxicity probably exist, and ordinary vitamin doses may harm occasional patients with genetic disorders.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1463588

  6. Vitamin D-binding protein influences total circulating levels of 1,25-dihydroxyvitamin D3 but does not directly modulate the bioactive levels of the hormone in vivo.

    PubMed

    Zella, Lee A; Shevde, Nirupama K; Hollis, Bruce W; Cooke, Nancy E; Pike, J Wesley

    2008-07-01

    Mice deficient in the expression of vitamin D-binding protein (DBP) are normocalcemic despite undetectable levels of circulating 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. We used this in vivo mouse model together with cells in culture to explore the impact of DBP on the biological activity of 1,25(OH)(2)D(3). Modest changes in the basal expression of genes involved in 1,25(OH)(2)D(3) metabolism and calcium homeostasis were observed in vivo; however, these changes seemed unlikely to explain the normal calcium balance seen in DBP-null mice. Further investigation revealed that despite the reduced blood levels of 1,25(OH)(2)D(3) in these mice, tissue concentrations were equivalent to those measured in wild-type counterparts. Thus, the presence of DBP has limited impact on the extracellular pool of 1,25(OH)(2)D(3) that is biologically active and that accumulates within target tissues. In cell culture, in contrast, the biological activity of 1,25(OH)(2)D(3) is significantly impacted by DBP. Here, although DBP deficiency had no effect on the activation profile itself, the absence of DBP strongly reduced the concentration of exogenous 1,25(OH)(2)D(3) necessary for transactivation. Surprisingly, analogous studies in wild-type and DBP-null mice, wherein we explored the activity of exogenous 1,25(OH)(2)D(3), produced strikingly different results as compared with those in vitro. Here, the carrier protein had virtually no impact on the distribution, uptake, activation profile, or biological potency of the hormone. Collectively, these experiments suggest that whereas DBP is important to total circulating 1,25(OH)(2)D(3) and sequesters extracellular levels of this hormone both in vivo and in vitro, the binding protein does not influence the hormone's biologically active pool. PMID:18372326

  7. Dioxin-induced up-regulation of the active form of vitamin D is the main cause for its inhibitory action on osteoblast activities, leading to developmental bone toxicity

    SciTech Connect

    Nishimura, Noriko [Research Center for Environmental Risk, National Institute for Environmental Studies, Tsukuba 305-8506 (Japan)], E-mail: noriko.nishimura@nies.go.jp; Nishimura, Hisao [Human Sciences, Aichi Mizuho University, Toyota 470-0394 (Japan); Ito, Tomohiro [Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba 305-8506 (Japan); Miyata, Chie [Research Center for Environmental Risk, National Institute for Environmental Studies, Tsukuba 305-8506 (Japan); College of Environmental Health, Azabu University, Sagamihara 229-8501, Kanagawa (Japan); Izumi, Keiko [FINETEC, Kitasenri 120-0036 (Japan); Fujimaki, Hidekazu [Research Center for Environmental Risk, National Institute for Environmental Studies, Tsukuba 305-8506 (Japan); Matsumura, Fumio [Department of Environmental Toxicology and Center for Environmental Health Sciences, University of California, Davis, California 95616 (United States)

    2009-05-01

    Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) is known to cause bone toxicity, particularly during animal development, although its action mechanism to cause this toxicity has yet to be elucidated. Mouse pups were exposed to TCDD via dam's milk that were administered orally with 15 {mu}g TCDD/kg b.w. on postnatal day 1. Here we report that TCDD causes up-regulation of vitamin D 1{alpha}-hydroxylase in kidney, resulting in a 2-fold increase in the active form of vitamin D, 1,25-dihydroxyvitamin D{sub 3}, in serum. This action of TCDD is not caused by changes in parathyroid hormone, a decrease in vitamin D degrading enzyme, vitamin D 24-hydroxylase, or alterations in serum Ca{sup 2+} concentration. Vitamin D is known to affect bone mineralization. Our data clearly show that TCDD-exposed mice exhibit a marked decrease in osteocalcin and collagen type 1 as well as alkaline phosphatase gene expression in tibia by postnatal day 21, which is accompanied with a mineralization defect in the tibia, lowered activity of osteoblastic bone formation, and an increase in fibroblastic growth factor-23, a sign of increased vitamin D effect. Despite these significant effects of TCDD on osteoblast activities, none of the markers of osteoclast activities was found to be affected. Histomorphometry confirmed that osteoblastic activity, but not bone resorption activity, was altered by TCDD. A prominent lesion commonly observed in these TCDD-treated mice was impaired bone mineralization that is characterized by an increased volume and thickness of osteoids lining both the endosteum of the cortical bone and trabeculae. Together, these data suggest that the impaired mineralization resulting from reduction of the osteoblastic activity, which is caused by TCDD-induced up-regulation of vitamin D, is responsible for its bone developmental toxicity.

  8. The effects of vitamin D2 or D3 supplementation on glycaemic control and related metabolic parameters in people at risk of type 2 diabetes: protocol of a randomised double-blind placebo-controlled trial

    PubMed Central

    2013-01-01

    Background The global prevalence of type 2 diabetes is increasing. Effective strategies to address this public health challenge are currently lacking. A number of epidemiological studies have reported associations between low concentrations of 25-hydroxy vitamin D and the incidence of diabetes, but a causal link has not been established. We investigate the effect of vitamin D supplementation on the metabolic status of individuals at increased risk of developing type 2 diabetes. Methods/design In a randomised double-blind placebo-controlled trial individuals identified as having a high risk of type 2 diabetes (non-diabetic hyperglycaemia or positive diabetes risk score) are randomised into one of three groups and given 4 doses of either placebo, or 100,000 IU Vitamin D2 (ergocalciferol) or 100,000 IU Vitamin D3 (cholecalciferol) at monthly intervals. The primary outcome measure is the change in glycated haemoglobin level between baseline and 4 months. Secondary outcome measures include blood pressure, lipid levels, apolipoproteins, highly sensitive C-reactive protein, parathyroid hormone (PTH) and safety of supplementation. and C-reactive protein. The trial is being conducted at two sites (London and Cambridge, U.K.) and a total of 342 participants are being recruited. Discussion Trial data examining whether supplementation of vitamin D improves glycaemic status and other metabolic parameters in people at risk of developing type 2 diabetes are sparse. This trial will evaluate the causal role of vitamin D in hyperglycaemia and risk of type 2 diabetes. Specific features of this trial include recruitment of participants from different ethnic groups, investigation of the relative effectiveness and safety of vitamin D2 and D3 and an evidence based approach to determination of the dose of supplementation. Trial registration EudraCT2009-011264-11; ISRCTN86515510 PMID:24152375

  9. Consequences of a Deficit in Vitamin B6 Biosynthesis de Novo for Hormone Homeostasis and Root Development in Arabidopsis1[OPEN

    PubMed Central

    Boycheva, Svetlana; Dominguez, Ana; Rolcik, Jakub; Boller, Thomas; Fitzpatrick, Teresa B.

    2015-01-01

    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

  10. Differential expression and regulation of Klotho by paricalcitol in the kidney, parathyroid, and aorta of uremic rats.

    PubMed

    Ritter, Cynthia S; Zhang, Sarah; Delmez, James; Finch, Jane L; Slatopolsky, Eduardo

    2015-06-01

    Klotho plays an important role in the pathogenesis of cardiovascular disease in chronic kidney disease (CKD). Klotho is highly expressed in the kidney and parathyroid glands, but its presence in the vasculature is debated. Renal Klotho is decreased in CKD, but the effect of uremia on Klotho in other tissues is not defined. The effect of vitamin D receptor activator therapy in CKD on the expression of Klotho in various tissues is also in debate. In uremic rats (surgical 5/6th nephrectomy model), we compared 3 months of treatment with and without paricalcitol on Klotho immunostaining in the kidney, parathyroid glands, and aorta. With uremia, Klotho was unchanged in the parathyroid, significantly decreased in the kidney (66%) and the intimal-medial area of the aorta (69%), and significantly increased in the adventitial area of the aorta (67%) compared with controls. Paricalcitol prevented the decrease of Klotho in the kidney, increased expression in the parathyroid (31%), had no effect in the aortic media, but blunted the increase of Klotho in the aortic adventitia. We propose that fibroblasts are responsible for the expression of Klotho in the adventitia. In hyperplastic human parathyroid tissue from uremic patients, Klotho was higher in oxyphil compared with chief cells. Thus, under our conditions of moderate CKD and mild-to-moderate hyperphosphatemia in rats, the differential expression of Klotho and its regulation by paricalcitol in uremia is tissue-dependent. PMID:25692955

  11. Genome-wide Analysis of the VDR/RXR Cistrome in Osteoblast Cells Provides New Mechanistic Insight into the Actions of the Vitamin D Hormone

    PubMed Central

    Meyer, Mark B.; Goetsch, Paul D.; Pike, J. Wesley

    2010-01-01

    The vitamin D receptor (VDR) mediates the actions of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in target cells and tissues by orchestrating the expression of gene networks responsible for vitamin D-induced phenotypes. The molecular mechanisms of these regulatory systems have been studied for decades under the principle that transcriptional regulation occurs near the transcriptional start site of the gene. However, this now appears to be an outdated view of transcriptional control. In this study, we examined the genome-wide chromatin immunoprecipitation on microarray (ChIP-chip) across pre-osteoblastic cells for VDR, retinoid X receptor (RXR), RNA polymerase II, and histone H4 acetylation (H4ac). We uncovered potential regulatory mechanisms for genes important to osteoblast biology as well as skeletal formation under the control of 1,25(OH)2D3. We found that VDR, along with RXR and H4ac, binds to distal regions 43% of the time; and within gene introns and exons 44%, leaving only 13% of activation at traditional promoter regions. Here, we briefly summarize our findings for all the VDR/RXR cis-acting transcriptional elements (VDR/RXR cistrome) in pre-osteoblastic cells, MC3T3-E1, provide a few examples of this dynamic control by VDR and 1,25(OH)2D3, and demonstrate that distal transcriptional control contributes to the majority of vitamin D3-mediated transcription. PMID:20171278

  12. The renaissance of vitamin D.

    PubMed

    Wierzbicka, Justyna; Piotrowska, Anna; ?mijewski, Micha? A

    2014-01-01

    There is no doubt that vitamin D plays a crucial role in the maintenance of musculoskeletal system. But the function of this ancient molecule presumably ranges far beyond hormone-like regulation, as it could be generated by simple unicellular organisms. First, we are going to discuss the role of vitamin D as a global regulator of homeostasis from a historical perspective, but later we will focus on current views and its relevance to human physiology and pathology. Three milestones are defining the impact of vitamin D on science and humanity. Firstly, discovery that vitamin D is the cure for rickets, brought us supplementation programs and rapid irradiation of this devastating disease. Secondly, detail description of photoproduction of vitamin D, its subsequent metabolism and interaction with vitamin D receptor VDR, provided mechanistic background for future discoveries. Finally, recent large epidemiological studies provided indirect, but strong evidence that optimal level of vitamin D in serum has beneficial effects on our health and protects us from multiple diseases, including cancer. Furthermore, existence of alternative pathways of vitamin D metabolism and multiple intracellular targets broadens our understanding of its physiological activities and offers new and very promising tools for prophylactics and treatment of many diseases of civilization. Although vitamin D (and its derivatives) should not be regarded as a cure-all for every human disease, its beneficial effects on the human health have to be taken under consideration. PMID:25566549

  13. Vitamin D and colon cancer

    PubMed Central

    Klampfer, Lidija

    2014-01-01

    Calcitriol, 1?, 25-dihydroxyvitamin D3 (1,25 (OH)2D3), the most active form of vitamin D, is a pleotropic hormone with a wide range of biological activities. Due to its ability to regulate calcium and phosphate metabolism, 1,25D3 plays a major role in bone health. In addition, 1,25D3 binds to the vitamin D receptor and thereby regulates the expression of a number of genes which control growth, differentiation and survival of cancer cells. In agreement, the levels of vitamin D3 appear to be an essential determinant for the development and progression of colon cancer and supplementation with vitamin D3 is effective in suppressing intestinal tumorigenesis in animal models. Vitamin D3 has been estimated to lower the incidence of colorectal cancer by 50%, which is consistent with the inverse correlation between dietary vitamin D3 intake or sunlight exposure and human colorectal cancer. Several studies confirmed that increasing vitamin D3 lowers colon cancer incidence, reduces polyp recurrence, and that sufficient levels of vitamin D3 are associated with better overall survival of colon cancer patients. Vitamin D regulates the homeostasis of intestinal epithelium by modulating the oncogenic Wnt signaling pathway and by inhibiting tumor-promoting inflammation. Both activities contribute to the ability of 1,25D3 to prevent the development and progression of colon cancer. PMID:25400874

  14. Thalamic calcication in vitamin D receptor knockout mice

    E-print Network

    Kalueff, Allan V.

    Thalamic calci˘cation in vitamin D receptor knockout mice Allan Kalueˇa , Elena Losevaa , Hannu (TAYS, Finland) and the Academy of Finland. Received 3 February 2006; accepted15 February 2006 Vitamin D is a steroid hormone with many important functions in the brain, mediated through the nuclear vitamin D

  15. A case of congenital agenesis of the common carotid artery associated with an ectopic parathyroid adenoma mimicking a carotid body tumor.

    PubMed

    Malm, Ian-James; Olcott, Clara M; Chan, Jason Y K; Loyo, Myriam; Kim, Young J

    2013-01-01

    Ectopic parathyroid adenomas can be encountered during four gland explorations, but nearly 80% of adenomas are localized with ultrasound and sestamibi imaging. Ectopic adenomas are thought to arise from abnormal migration during development. As a cervical congenital anomaly, common carotid artery agenesis is an extremely rare anomaly characterized by separate origins of the internal and external carotid arteries directly from the aortic arch. Here we present a case of a 75 year old man with primary hyperparathyroidism who was found to have congenital agenesis of the common carotid artery associated with an ectopic parathyroid adenoma within the parapharyngeal space, which mimicked a carotid body tumor based on location and imaging. The successful identification and resection of the ectopic parathyroid adenoma presented here demonstrate the importance of preoperative imaging studies to allow appropriate operative planning as well as the utility of intraoperative parathyroid hormone assay in predicting cure during surgery. PMID:23993711

  16. Evolutionary selection across the nuclear hormone receptor superfamily with a focus on the NR1I subfamily (vitamin D, pregnane X, and constitutive androstane receptors)

    Microsoft Academic Search

    Matthew D Krasowski; Kazuto Yasuda; Lee R Hagey; Erin G Schuetz

    2005-01-01

    BACKGROUND: The nuclear hormone receptor (NR) superfamily complement in humans is composed of 48 genes with diverse roles in metabolic homeostasis, development, and detoxification. In general, NRs are strongly conserved between vertebrate species, and few examples of molecular adaptation (positive selection) within this superfamily have been demonstrated. Previous studies utilizing two-species comparisons reveal strong purifying (negative) selection of most NR

  17. Vitamin D activities for health outcomes.

    PubMed

    Morris, Howard A

    2014-05-01

    Reports describing significant health risks due to inadequate vitamin D status continue to generate considerable interest amongst the medical and lay communities alike. Recent research on the various molecular activities of the vitamin D system, including the nuclear vitamin D receptor and other receptors for 1,25-dihydroxyvitamin D and vitamin D metabolism, provides evidence that the vitamin D system carries out biological activities across a wide range of tissues similar to other nuclear receptor hormones. This knowledge provides physiological plausibility of the various health benefits claimed to be provided by vitamin D and supports the proposals for conducting clinical trials. The vitamin D system plays critical roles in the maintenance of plasma calcium and phosphate and bone mineral homeostasis. Recent evidence confirms that plasma calcium homeostasis is the critical factor modulating vitamin D activity. Vitamin D activities in the skeleton include stimulation or inhibition of bone resorption and inhibition or stimulation of bone formation. The three major bone cell types, which are osteoblasts, osteocytes and osteoclasts, can all respond to vitamin D via the classical nuclear vitamin D receptor and metabolize 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D to activate the vitamin D receptor and modulate gene expression. Dietary calcium intake interacts with vitamin D metabolism at both the renal and bone tissue levels to direct either a catabolic action on the bone through the endocrine system when calcium intake is inadequate or an anabolic action through a bone autocrine or paracrine system when calcium intake is sufficient. PMID:24790904

  18. Relationship between vitamin D and inflammatory markers in older individuals.

    PubMed

    De Vita, Francesca; Lauretani, Fulvio; Bauer, Juergen; Bautmans, Ivan; Shardell, Michelle; Cherubini, Antonio; Bondi, Giuliana; Zuliani, Giovanni; Bandinelli, Stefania; Pedrazzoni, Mario; Dall'Aglio, Elisabetta; Ceda, Gian Paolo; Maggio, Marcello

    2014-01-01

    In older persons, vitamin D insufficiency and a subclinical chronic inflammatory status frequently coexist. Vitamin D has immune-modulatory and in vitro anti-inflammatory properties. However, there is inconclusive evidence about the anti-inflammatory role of vitamin D in older subjects. Thus, we investigated the hypothesis of an inverse relationship between 25-hydroxyvitamin D (25(OH)D) and inflammatory markers in a population-based study of older individuals. After excluding participants with high-sensitivity C-reactive protein (hsCRP)???10 mg/dl and those who were on chronic anti-inflammatory treatment, we evaluated 867 older adults ?65 years from the InCHIANTI Study. Participants had complete data on serum concentrations of 25(OH)D, hsCRP, tumor necrosis factor (TNF)-?, soluble TNF-? receptors 1 and 2, interleukin (IL)-1?, IL-1 receptor antagonist, IL-10, IL-18, IL-6, and soluble IL-6 receptors (sIL6r and sgp130). Two general linear models were fit (model 1-adjusted for age, sex, and parathyroid hormone (PTH); model 2-including covariates of model 1 plus dietary and smoking habits, physical activity, ADL disability, season, osteoporosis, depressive status, and comorbidities). The mean age was 75.1 ± 17.1 years ± SD. In model 1, log(25OH-D) was significantly and inversely associated with log(IL-6) (? ± SE = -0.11 ± 0.03, p = <0.0001) and log (hsCRP) (? ± SE = -0.04 ± 0.02, p = 0.04) and positively associated with log(sIL6r) (? ± SE = 0.11 ± 0.04, p = 0.003) but not with other inflammatory markers. In model 2, log (25OH-D) remained negatively associated with log (IL-6) (? ± SE = -0.10 ± 0.03, p = 0.0001) and positively associated with log(sIL6r) (? ± SE = 0.11 ± 0.03, p = 0.004) but not with log(hsCRP) (? ± SE = -0.01 ± 0.03, p = 0.07). 25(OH)D is independently and inversely associated with IL-6 and positively with sIL6r, suggesting a potential anti-inflammatory role for vitamin D in older individuals. PMID:25086618

  19. Imaging techniques in parathyroid surgery for primary hyperparathyroidism

    PubMed Central

    Mohebati, A.; Shaha, A.R.

    2011-01-01

    As more patients present with the incidental diagnosis of primary hyperparathyroidism due to biochemical screening, treatment guidelines have been developed for the treatment of hyperparathyroidism. Management of primary hyperparathyroidism has evolved in recent years with considerable interest in minimally invasive approaches. Successful localization of the diseased gland(s) by nuclear imaging and anatomical studies along with rapid intraoperative parathyroid hormone assay has allowed for focused and minimally invasive surgical approaches. Patients in whom the localization studies have identified single gland adenoma or unilateral disease are candidates for such focused approaches instead of the traditional approach of bilateral exploration. These imaging techniques have also been critical in the successful management of patients with persistent or recurrent disease. PMID:22154018

  20. Hydrosoluble vitamins.

    PubMed

    Chawla, Jasvinder; Kvarnberg, David

    2014-01-01

    The hydrosoluble vitamins are a group of organic substances that are required by humans in small amounts to prevent disorders of metabolism. Significant progress has been made in our understanding of the biochemical, physiologic and nutritional aspects of the water-soluble vitamins. Deficiency of these particular vitamins, most commonly due to inadequate nutrition, can result in disorders of the nervous system. Many of these disorders have been successfully prevented in developed countries; however, they are still common in developing countries. Of the hydrosoluble vitamins, the nervous system depends the most on vitamins B and C (ascorbic acid) for proper functioning. The B group vitamins include thiamin (vitamin B1), riboflavin (vitamin B2), niacin or niacinamide (vitamin B3), pantothenic acid (vitamin B5), pyridoxine or pyridoxal (vitamin B6) and cobalamin (vitamin B12). Clinical findings depend upon the deficiency of the underlying vitamin; generally, deficiency symptoms are seen from a combination rather than an isolated vitamin deficiency. True hereditary metabolic disorders and serious deficiency-associated diseases are rare and in general limited to particular geographic regions and high-risk groups. Their recognition is truly important as that determines the appropriate therapeutic management. The general availability of vitamins to practically everyone and several national health programs have saved many lives and prevented complications. However, there has been some apprehension for several decades about how harmless generous dosages of these vitamins are. Overt overdosages can cause vitamin toxicity affecting various body systems including the nervous system. Systemically, vitamin toxicity is associated with nonspecific symptoms, such as nausea, vomiting, diarrhea, and skin rash which are common with any acute or chronic vitamin overdose. At a national level, recommended daily allowances for vitamins become policy statements. Nutrition policy has far reaching implications in the food industry, in agriculture, and in food provision programs. Overall, water-soluble vitamins are complex molecular structures and even today, many areas of vitamin biochemistry still need to be explored. Many readers might be of the opinion that the classic forms of nutritional deficiency diseases have faded into the background of interesting history. This has caused their diverse symptoms to be neglected by most modern physicians since vitamin enrichment of many foods automatically erases them from their consideration in differential diagnosis. Vitamin B12 and folic acid deficiencies are discussed in other chapters. PMID:24365359

  1. Parathyroid carcinoma: Diagnostic criteria, classification, evaluation.

    PubMed

    Do Cao, Christine; Aubert, Sébastien; Trinel, Clémentine; Odou, Marie-Françoise; Bayaram, Michael; Patey, Martine

    2015-05-01

    Parathyroid carcinoma is a little-known cancer, difficult to diagnose. We focus this short review on the current diagnostic criteria, the classification and the evaluation tools for this cancer based on latest publications. PMID:25916757

  2. Identification of differentially expressed microRNA in parathyroid tumors

    PubMed Central

    Rahbari, Reza; Holloway, Alisha K.; He, Mei; Khanafshar, Elham; Clark, Orlo H.; Kebebew, Electron

    2012-01-01

    Background The molecular factors that control parathyroid tumorigenesis are poorly understood. In the absence of local invasion or metastasis, distinguishing benign from malignant parathyroid neoplasm is difficult on histologic examination. We studied the miRNA profile in normal, hyperplastic, and benign and malignant parathyroid tumors to better understand the molecular factors that may play a role in parathyroid tumorigenesis and that may serve as diagnostic markers for parathyroid carcinoma. Methods MiRNA arrays containing 825 human microRNAs with 4 duplicate probes per miRNA were used to profile parathyroid tumor (12 adenomas, 9 carcinomas, and 15 hyperplastic) samples normalized to 4 reference normal parathyroid glands. Differentially expressed miRNA were validated by real-time quantitative TaqMan PCR. Results One hundred and fifty six miRNAs in parathyroid hyperplasia, 277 microRNAs in parathyroid adenoma, and 167 microRNAs in parathyroid carcinomas were significantly dysregulated as compared to normal parathyroid glands (FDR < 0.05). By supervised clustering analysis, all parathyroid carcinomas clustered together. Three miRNAs (miR-26b, miR-30b and miR-126*) were significantly dysregulated between parathyroid carcinoma and parathyroid adenoma. Receiver operative characteristic curve analysis showed mir-126* was the best diagnostic marker, with an area under the curve of 0.776. MiRNAs are differentially expressed in parathyroid neoplasms. Conclusions Most miRNA are downregulated in parathyroid carcinoma while in parathyroid hyperplasia most miRNA are upregulated. MiRNA profiling shows distinct differentially expressed miRNAs by tumor type which may serve as helpful adjunct to distinguish parathyroid adenoma from carcinoma. PMID:21086055

  3. 25-Hydroxyvitamin D3 1?-hydroxylase expression in breast cancer and use of non-1?-hydroxylated vitamin D analogue

    PubMed Central

    Segersten, Ulrika; Holm, Pernille Kaae; Björklund, Peyman; Hessman, Ola; Nordgren, Hans; Binderup, Lise; Ĺkerström, Göran; Hellman, Per; Westin, Gunnar

    2005-01-01

    Introduction The cytochrome P450 mitochondrial enzyme 25-hydroxyvitamin D3 1?-hydroxylase (1?-hydroxylase) of renal tubule cells hydroxylates the major circulating form of vitamin D (25(OH)D3) to the active systemic hormone 1,25(OH)2D3. Local production of 1,25(OH)2D3 appears to occur also at other sites where 1?-hydroxylase is expressed for autocrine/paracrine regulation. To reduce risks of hypercalcemia during treatment with vitamin D, we have previously suggested use of non-1?-hydroxylated vitamin D analogues to target tissues where 1?-hydroxylase is expressed, including the parathyroid glands in secondary hyperparathyroidism. The present study was undertaken to examine expression of 1?-hydroxylase in breast cancer and to investigate whether a non-1?-hydroxylated vitamin D analogue displayed biological function. In addition, expression of the 25-hydroxyvitamin D3 24-hydroxylase (24-hydroxylase) and the vitamin D receptor (VDR) was investigated. Methods The expression of 1?-hydroxylase, 24-hydroxylase and VDR was investigated in breast cancer specimens (n = 19) and normal breast tissues (n = 10) by immunohistochemistry and/or RT-PCR. Consecutive cryosections of 6 ?m essentially free of immune cells were used in the analyses. The effect of vitamin D analogues on transcriptional activation was analyzed in transiently transfected MCF-7 breast cancer cells. Results 1?-hydroxylase protein was demonstrated in 79% and 100% of breast cancer specimens and normal breast, respectively. The overall relative mRNA levels of 1?-hydroxylase and 24-hydroxylase in normal breast compared to breast tumors were: 1?-hydroxylase, 1 ± 0.07 versus 0.7 ± 0.05, respectively (p < 0.001); 24-hydroxylase, 1 ± 0.08 verus 2.1 ± 0.2, respectively (p < 0.001). The VDR was expressed in 95% of the tumors as expected, with mRNA levels of 1 ± 0.09 and 1.4 ± 0.12 (p < 0.05) in breast cancer and normal breast, respectively. The ketoconazole-sensitive transcription activation potential of the non-1?-hydroxylated vitamin D analogue prodrug of EB1089 (EB1285) was demonstrated in MCF-7 cells, which express 1?-hydroxylase. The activity of EB1285 was about 20% of 1,25(OH)2D3. Conclusion These results demonstrate nearly normal expression levels of 1?-hydroxylase, 24-hydroxylase and VDR in the majority of investigated breast cancer specimens. A non-1?-hydroxylated vitamin D analogue displayed activity in breast cancer cells. Such analogues may present future therapeutic options for proliferative disorders where 1?-hydroxylase is expressed. PMID:16280049

  4. Effect of Vitamin D on basal and Luteinizing Hormone (LH) induced testosterone production and mitochondrial dehydrogenase activity in cultured Leydig cells from immature and mature rams.

    PubMed

    Huang, Yang; Jin, Hui; Chen, Jianwei; Jiang, Xiaolong; Li, Pengfei; Ren, Youshe; Liu, Wenzhong; Yao, Jianbo; Folger, Joseph K; Smith, George W; Lv, Lihua

    2015-07-01

    The objectives of this study were to investigate the potential effects of 1?,25-(OH)2VD3 (biologically active form of Vitamin D) on basal and LH-induced testosterone production and mitochondrial dehydrogenase activity in Leydig cells from immature and mature rams cultured in vitro. Leydig cells were isolated from testes of immature and mature rams, treated without (control) or with increasing concentrations of LH (1, 10, 100ng/ml) and/or 1?,25-(OH)2VD3 (1, 10, 100nM). After 24h, concentrations of testosterone in culture media were measured. After 96h, mitochondrial dehydrogenase activity in Leydig cells were measured. In immature and mature ram Leydig cells, treatment with 10 and 100ng/ml LH increased testosterone production and mitochondrial dehydrogenase activity. Treatment with 1?,25-(OH)2VD3 in the absence of LH did not increase testosterone production, but 10 and 100nM 1?,25-(OH)2VD3 increased LH induced testosterone production for both immature and mature ram Leydig cells. Treatment with all doses of 1?,25-(OH)2VD3 in the absence of LH and 10 and 100ng/ml LH in the absence of 1?,25-(OH)2VD3 increased mitochondrial dehydrogenase activity for cultured Leydig cells from immature and mature rams and 1 and 10nM 1?,25-(OH)2VD3 treatment enhanced the LH induced increase in mitochondrial dehydrogenase activity. Result demonstrate Vitamin D3 induced regulation of function of Leydig cells from immature and mature rams cultured in the presence or absence of LH and support a potential role for Vitamin D3 in regulation of gonadal function in rams. PMID:26024964

  5. 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

    McGinnis, William Sams

    1967-01-01

    feeding was not attained until November 15, 1963. The cattle were given the feed treatments shown in Table 1 one month after arriving at the Texas A &M University Plantation at College Station. 10 TABLE 1. THE EXPERIMENTAL PLAI4 FOR PROJECT S-1171... dicalciurn phosphate j ? 1 denotes DES i - 2 denotes dipotassiurn phosphate j ? 2 denotes Synovex i ? 3 denotes ammonium chloride j - 3 denotes vitamin A i ? 4 denotes control j ? 4 denotes control When a significant difference was found by use...

  6. Progressive Hearing Loss in Mice with a Mutated Vitamin D Receptor Gene

    Microsoft Academic Search

    Jing Zou; Anna Minasyan; Tiina Keisala; Ya Zhang; Jing-Huan Wang; Yan-Ru Lou; Alan Kalueff; Ilmari Pyykkö; Pentti Tuohimaa

    2008-01-01

    Background: Both hypo- and hypervitaminosis D can cause sensorineural hearing loss, and aural symptoms due to vitamin D insufficiency are especially common during gravidity. Hormonal forms of vitamin D regulate transcription by binding with the high-affinity vitamin D receptor (VDR). Objective: To assess the effects of impaired vitamin D action in VDR knockout (KO) mice on hearing, cochlear morphology, and

  7. Vitamin K

    MedlinePLUS

    ... and to treat bleeding caused by medications including salicylates, sulfonamides, quinine, quinidine, or antibiotics. Vitamin K is ... 4-Amino-2-Methyl-1-Naphthol, Fat-Soluble Vitamin, Menadiol Acetate, ... Sodium Bisulfite, Menaquinone, Ménaquinone, Menatetrenone, Menatétrenone, ...

  8. Vitamin K

    MedlinePLUS

    Vitamin K helps make four of the 13 proteins needed for blood clotting. Its role in maintaining ... warfarin (Coumadin) must be careful to keep their vitamin K intake stable. Lately, researchers have demonstrated that ...

  9. Vitamin D

    MedlinePLUS

    ... a condition known as rickets in children and osteomalacia in adults. Vitamin D is important to the ... children. In adults, vitamin D deficiency leads to osteomalacia, causing bone pain and muscle weakness. What are ...

  10. Vitamin C

    MedlinePLUS

    Vitamin C is an antioxidant. It is important for your skin, bones, and connective tissue. It promotes healing and helps the body absorb iron. Vitamin C comes from fruits and vegetables. Good sources ...

  11. Vitamin A

    MedlinePLUS

    Vitamin A does much more than help you see in the dark. It stimulates the production and activity ... had researchers exploring for years the relationship between vitamin A and cancer. Specifically, researchers looked at whether people ...

  12. Vitamin C

    MedlinePLUS

    ... high doses of vitamin C could worsen iron overload and damage body tissues. The upper limits for ... of a specific vitamin or mineral. For more information on building a healthy diet, refer to the ...

  13. Effects of Oral, Vaginal, and Transdermal Hormonal Contraception on Serum Levels of Coenzyme Q10, Vitamin E, and Total Antioxidant Activity

    PubMed Central

    Palan, Prabhudas R.; Strube, Felix; Letko, Juraj; Sadikovic, Azra; Mikhail, Magdy S.

    2010-01-01

    The use of the transdermal contraceptive patch is associated with greater bioavailability of ethinyl estradiol (EE) compared with contraceptive vaginal ring or oral contraceptives (OC). We compared the influences of three contraceptive methods (OC, vaginal ring, and transdermal patch) on serum levels of coenzyme Q10, ?-tocopherol, ?-tocopherol and total antioxidant capacity in premenopausal women. Blood samples from 30 premenopausal women who used hormonal contraception for at least 4 months were collected. Forty subjects who did not use any contraception were studied as control. Serum levels of coenzyme Q10, ?-tocopherol and ?-tocopherol were measured by high-pressure liquid chromatography. Serum samples were also assayed for total antioxidant capacity (TAOC). Serum levels of coenzyme Q10 and ?-tocopherol were found to be significantly lower (P < .05) in all three contraceptive users compared with controls. Contraceptive patch users had the lowest levels of coenzyme Q10 levels compared with normal subjects. Serum TAOC levels were significantly lower (P < .05) among the contraceptive user groups. Alterations in coenzyme Q10 and ?-tocopherol induced by hormonal contraception and the potential effect(s) of exogenous ovarian hormones should be taken into consideration in future antioxidant research. PMID:20814444

  14. Effects of oral, vaginal, and transdermal hormonal contraception on serum levels of coenzyme q(10), vitamin e, and total antioxidant activity.

    PubMed

    Palan, Prabhudas R; Strube, Felix; Letko, Juraj; Sadikovic, Azra; Mikhail, Magdy S

    2010-01-01

    The use of the transdermal contraceptive patch is associated with greater bioavailability of ethinyl estradiol (EE) compared with contraceptive vaginal ring or oral contraceptives (OC). We compared the influences of three contraceptive methods (OC, vaginal ring, and transdermal patch) on serum levels of coenzyme Q(10), alpha-tocopherol, gamma-tocopherol and total antioxidant capacity in premenopausal women. Blood samples from 30 premenopausal women who used hormonal contraception for at least 4 months were collected. Forty subjects who did not use any contraception were studied as control. Serum levels of coenzyme Q(10), alpha-tocopherol and gamma-tocopherol were measured by high-pressure liquid chromatography. Serum samples were also assayed for total antioxidant capacity (TAOC). Serum levels of coenzyme Q(10) and alpha-tocopherol were found to be significantly lower (P < .05) in all three contraceptive users compared with controls. Contraceptive patch users had the lowest levels of coenzyme Q(10) levels compared with normal subjects. Serum TAOC levels were significantly lower (P < .05) among the contraceptive user groups. Alterations in coenzyme Q(10) and alpha-tocopherol induced by hormonal contraception and the potential effect(s) of exogenous ovarian hormones should be taken into consideration in future antioxidant research. PMID:20814444

  15. The role of vitamin D in asthma.

    PubMed

    Luong, Khanh vinh quoc; Nguyen, Lan Thi Hoŕng

    2012-04-01

    Vitamin D metabolites are important immune-modulatory hormones and are able to suppress Th2-mediated allergic airway disease. Some genetic factors that may contribute to asthma are regulated by vitamin D, such as vitamin D receptor (VDR), human leukocyte antigen genes (HLA), human Toll-like receptors (TLR), matrix metalloproteinases (MMPs), a disintegrin and metalloprotein-33 (ADAM-33), and poly(ADP-ribosyl) polymerase- 1 (PARP-1). Vitamin D has also been implicated in asthma through its effects on the obesity, bacillus Calmettee Guérin (BCG) vaccination and high vitamin D level, vitamin D supplement, checkpoint protein kinase 1 (Chk1), plasminogen activator inhibitor-1 (PAI-1) and gamma delta T cells (gdT). Vitamin D plays a role in asthma and exerts its action through either genomic and/or non-genomic ways. PMID:22532985

  16. Vitamin Analysis

    NASA Astrophysics Data System (ADS)

    Pegg, Ronald B.; Landen, W. O.; Eitenmiller, Ronald R.

    Vitamins are defined as relatively low-molecular-weight compounds which humans, and for that matter, any living organism that depends on organic matter as a source of nutrients, require small quantities for normal metabolism. With few exceptions, humans cannot synthesize most vitamins and therefore need to obtain them from food and supplements. Insufficient levels of vitamins result in deficiency diseases [e.g., scurvy and pellagra, which are due to the lack of ascorbic acid (vitamin C) and niacin, respectively].

  17. Vitamin D

    Microsoft Academic Search

    Michael F. Holick

    2002-01-01

    Vitamin D evolved for the development and maintenance of a healthy vertebrate skeleton. Vitamin D (1,25-dihydroxyvitamin D)\\u000a maintains serum calcium and phosphorus levels in a physiologic range for skeleton mineralization. Vitamin D increases intestinal\\u000a calcium absorption, stimulating osteoblast function and mobilizing osteoclast precursor cells to enhance bone calcium mobilization.\\u000a Most vitamin D for the human requirement comes from exposure to

  18. Menin and TGF-beta superfamily member signaling via the Smad pathway in pituitary, parathyroid and osteoblast.

    PubMed

    Hendy, G N; Kaji, H; Sowa, H; Lebrun, J-J; Canaff, L

    2005-06-01

    PITUITARY: Menin is a Smad3-interacting protein; inactivation of menin blocks transforming growth factor (TGF)-beta and activin signaling, antagonizing their growth-inhibitory properties in anterior pituitary cells. Menin is also required for the activin-induced inhibition of prolactin expression mediated by the Smads and the transcription factor, Pit-1. The interaction between menin and Smad3 is direct. PARATHYROID: In cultured parathyroid cells from uremic hemodialysis patients, in which the menin signaling pathways are probably still intact, menin inactivation achieved by menin antisense oligonucleotides leads to loss of TGF-beta inhibition of parathyroid cell proliferation and parathyroid hormone (PTH) secretion. Moreover, TGF-beta does not affect the proliferation and PTH production of parathyroid cells from multiple endocrine neoplasia type 1 (MEN1) patients. OSTEOBLAST: Men1-null mouse fetuses that die at day 12 or earlier have cranial/facial hypoplasias implicating menin in bone development. Menin is required for the commitment of multipotential mesenchymal stem cells into the osteoblast lineage. This is achieved by menin interacting physically and functionally with bone morphogenetic protein (BMP)-2 regulated Smads, such as Smad1 and Smad5, and the key osteoblast regulator, Runx2. These interactions are lost as the committed osteoblasts differentiate further at which time menin interacts with Smad3, mediating the negative regulation of Runx2 by TGF-beta. Menin also suppresses osteoblast maturation, partly by inhibiting the differentiation actions of JunD. PMID:16001330

  19. Vitamin A

    MedlinePLUS

    Vitamin A plays a role in your Vision Bone growth Reproduction Cell functions Immune system Vitamin A is an antioxidant. It can come from plant ... Animal sources include liver and whole milk. Vitamin A is also added to foods like cereals. Vegetarians, ...

  20. Vitamin D

    MedlinePLUS

    Vitamin D helps your body absorb calcium. Calcium is one of the main building blocks of bone. A lack of vitamin D can lead to bone diseases such as osteoporosis or rickets. Vitamin D also has a role in your nerve, ...

  1. Vitamin K

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin K, a fat-soluble vitamin, is an enzyme cofactor for post-translation modification of specific glutamate residues that are converted into '-carboxyglutamic acid (Gla) residues by a vitamin K-dependent (VKD) carboxylase. Seven VKD coagulation proteins are synthesized in the liver. The extra-he...

  2. Correlates of parathyroid hormone concentration in hemodialysis patients

    E-print Network

    2013-01-01

    types of vascular access (catheter, graft, ?stula andWidowed Vascular access Catheter (reference) AVF Graft OtherGraft Other K t /V (single pool) Residual renal function (Kru) Marital status (%) Vascular

  3. Noninvasive Imaging of Osteoclasts in Parathyroid HormoneInduced Osteolysis

    E-print Network

    Larson-Prior, Linda

    in many types of cancer. An imaging agent targeting osteoclasts, which are upregulated in osteolytic sites of cancer metastasis (1). It has been reported that in 75% of patients with metastatic breast). Breast cancer cells in bone stimulate recruitment of osteoclasts, resulting in osteolysis (3). Bone

  4. Different vitamin D receptor agonists exhibit differential effects on endothelial function and aortic gene expression in 5/6 nephrectomized rats.

    PubMed

    Wu-Wong, J Ruth; Li, Xinmin; Chen, Yung-Wu

    2015-04-01

    Endothelial dysfunction, common in chronic kidney disease (CKD), significantly increases cardiovascular disease risk in CKD patients. This study investigates whether different vitamin D receptor agonists exhibit different effects on endothelial function and on aortic gene expression in an animal CKD model. The 5/6 nephrectomized (NX) rat was treated with or without alfacalcidol (0.02, 0.04 and 0.08?g/kg), paricalcitol (0.04 and 0.08?g/kg), or VS-105 (0.004, 0.01 and 0.16?g/kg). All three compounds at the test doses suppressed serum parathyroid hormone effectively. Alfacalcidol at 0.08?g/kg raised serum calcium significantly. Endothelial function was assessed by pre-contracting thoracic aortic rings with phenylephrine, followed by treatment with acetylcholine or sodium nitroprusside. Uremia significantly affected endothelial-dependent aortic relaxation, which was improved by all three compounds in a dose-dependent manner with alfacalcidol and paricalcitol exhibiting a lesser effect. DNA microarray analysis of aorta samples revealed that uremia impacted the expression of numerous aortic genes, many of which were normalized by the vitamin D analogs. Real-time RT-PCR analysis confirmed that selected genes such as Abra, Apoa4, Fabp2, Hsd17b2, and Hspa1b affected by uremia were normalized by the vitamin D analogs with alfacalcidol exhibiting less of an effect. These results demonstrate that different vitamin D analogs exhibit different effects on endothelial function and aortic gene expression in 5/6 NX rats. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. PMID:25500070

  5. Vitamin D Supplementation in Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Observational Studies and Randomized Controlled Trials

    PubMed Central

    Kandula, Praveen; Dobre, Mirela; Schold, Jesse D.; Schreiber, Martin J.; Mehrotra, Rajnish

    2011-01-01

    Summary Background and objectives Vitamin D deficiency is highly prevalent among patients with chronic kidney disease (CKD). The benefits and harms of vitamin D supplementation (ergocalciferol or cholecalciferol) were assessed in patients with nondialysis-dependent CKD, dialysis-dependent CKD, and renal transplant recipients. Design, setting, participants, & measurements MEDLINE (1966 to September 2009), SCOPUS (September 2009), and nephrology conference proceedings were searched for relevant observational and randomized controlled trials (RCTs). Treatment effects were summarized as mean differences (MDs) with 95% confidence intervals (CIs) using a random effects model. Separate analyses were conducted for observational studies and RCTs. Results Twenty-two studies (17 observational and 5 RCTs) were included. There was a significant improvement in 25-hydroxyvitamin D (MD 24.1 ng/ml, 95% CI 19.6 to 28.6) and an associated decline in parathyroid hormone (PTH) levels (MD ?41.7 pg/ml, 95% CI ?55.8 to ?27.7) among observational studies. PTH reduction was higher in dialysis patients. Among RCTs, there was a significant improvement in 25-hydroxyvitamin D (MD 14 ng/ml, 95% CI 5.6 to 22.4) and an associated decline in PTH levels (MD ?31.5 pg/ml, 95% CI ?57 to ?6.1). A low incidence of hypercalcemia and hyperphosphatemia was reported with vitamin D supplementation. Cardiovascular and skeletal effects of vitamin D supplementation have not been studied. Included studies were mostly of low to moderate quality. Conclusions Available evidence from low-to-moderate quality observational studies and fewer RCTs suggests that vitamin D supplementation improves biochemical endpoints. However, whether such improvements translate into clinically significant outcomes is yet to be determined. PMID:20876671

  6. Association between vitamin D insufficiency and tuberculosis in a vietnamese population

    PubMed Central

    2010-01-01

    Background Recent in vitro evidence suggests a link between vitamin D status and the risk of tuberculosis (TB). This study sought to examine the association between vitamin D status, parathyroid hormone (PTH) and the risk of TB in a Vietnamese population. Methods The study was designed as a matched case-control study, which involved 166 TB patients (113 men and 53 women), who were age-and-sex matched with 219 controls (113 men and 106 women). The average age of men and women was 49 and 50, respectively. TB was diagnosed by the presence of acid-fast bacilli on smears from sputum, and the isolation of M. tuberculosis. All patients were hospitalized for treatment in a TB specialist hospital. Controls were randomly drawn from the general community within the Ho Chi Minh, Vietnam. 25-hydroxyvitamin D [25(OH)D] and PTH was measured prior to treatment by an electrochemiluminescence immunoassay (ECLIA) on a Roche Elecsys. A serum level of 25(OH)D below 30 ng/mL was deemed to be vitamin D insufficient. Results The prevalence of vitamin D insufficiency was 35.4% in men with TB and 19.5% in controls (P = 0.01). In women, there were no significant differences in serum 25(OH)D and serum PTH levels between TB patients and controls. The prevalence of vitamin D insufficiency in women with TB (45.3%) was not significantly different from those without TB (47.6%; P = 0.91). However, in both genders, serum calcium levels in TB patients were significantly lower than in non-TB individuals. Smoking (odds ratio [OR] 1.25; 95% confidence interval [CI] 1.10 - 14.7), reduced 25(OH)D (OR per standard deviation [SD]: 1.14; 95% CI 1.07 - 10.7) and increased PTH (OR per SD 1.13; 95% CI 1.05 - 10.4) were independently associated with increased risk of TB in men. Conclusion These results suggest that vitamin D insufficiency was a risk factor for tuberculosis in men, but not in women. However, it remains to be established whether the association is a causal relationship. PMID:20973965

  7. Delayed Surgery for Parathyroid Adenoma Misdiagnosed as a Thyroid Nodule and Treated with Radiofrequency Ablation

    PubMed Central

    Kim, Ho-Su; Choi, Bong Hoi; Park, Jung Rang; Hahm, Jong Ryeal; Jung, Jung Hwa; Kim, Soo Kyoung; Kim, Sungsu; Kim, Kyong-Young; Chung, Soon Il

    2013-01-01

    Primary hyperparathyroidism occurs as a result of isolated parathyroid adenoma in 80% to 85% of all cases. A 99mtechnetium (99mTc) sestamibi scan or neck ultrasonography is used to localize the neoplasm prior to surgical intervention. A 53-year-old female was referred for the exclusion of metabolic bone disease. She presented with low back pain that had persisted for the past 6 months and elevated serum alkaline phosphatase (1,253 IU/L). Four years previously, she had been diagnosed at a local hospital with a 2.3-cm thyroid nodule, which was determined to be pathologically benign. Radiofrequency ablation was performed at the same hospital because the nodule was still growing during the follow-up period 2 years before the visit to our hospital, and the procedure was unsuccessful in reducing the size of the nodule. The results of the laboratory tests in our hospital were as follows: serum calcium, 14.6 mg/dL; phosphorus, 3.5 mg/dL; and intact parathyroid hormone (iPTH), 1,911 pg/mL. Neck ultrasonography and 99mTc sestamibi scan detected a 5-cm parathyroid neoplasm in the left lower lobe of the patient's thyroid; left parathyroidectomy was performed. This case indicated that thyroid ultrasonographers and pathologists need to be experienced enough to differentiate a parathyroid neoplasm from a thyroid nodule; 99mTc sestamibi scan, serum calcium, and iPTH levels can help to establish the diagnosis of parathyroid neoplasm. PMID:24396684

  8. Vitamin K and Vitamin D Status: Associations with Inflammatory Markers in the Framingham Offspring Study

    Microsoft Academic Search

    M. Kyla Shea; Sarah L. Booth; Joseph M. Massaro; Paul F. Jacques; Ralph B. D'Agostino; Bess Dawson-Hughes; Jose M. Ordovas; Christopher J. O'Donnell; Sekar Kathiresan; John F. Keaney; Ramachandran S. Vasan; Emelia J. Benjamin

    2008-01-01

    In vitro data suggest protective roles for vitamins K and D in inflammation. To examine associations between vitamins K and D and inflammation in vivo, the authors used multiple linear regression analyses, adjusted for age, sex, body mass index, triglyceride concentrations, use of aspirin, use of lipid-lowering medication, season, men- opausal status, and hormone replacement therapy. Participants were from the

  9. Structure and mechanism for recognition of peptide hormones by Class B G-protein-coupled receptors

    Microsoft Academic Search

    Kuntal Pal; Karsten Melcher; H Eric Xu

    2012-01-01

    Class B G-protein-coupled receptors (GPCRs) are receptors for peptide hormones that include glucagon, parathyroid hormone, and calcitonin. These receptors are involved in a wide spectrum of physiological activities, from metabolic regulation and stress control to development and maintenance of the skeletal system. As such, they are important drug targets for the treatment of diabetes, osteoporosis, and stress related disorders. Class

  10. Measuring Parathyroid Hormone (PTH) in Patients with Oxidative Stress – Do We Need a Fourth Generation Parathyroid Hormone Assay?

    PubMed Central

    Stoeva, Stanka; Reichetzeder, Christoph; Grön, Hans Jürgen; Lieker, Ina; Khadzhynov, Dmytro; Slowinski, Torsten; Roth, Heinz Jürgen

    2012-01-01

    Oxidation of PTH at methionine residues results in loss of biological activity. PTH may be oxidized in patients with renal disease. The aim of this study was to develop an assay considering oxidation of PTH. Oxidized hPTH was analyzed by high resolution nano-liquid chromatography coupled to ESI-FTT tandem mass spectrometry (nanoLC-ESI-FT-MS/MS) directly and after proteolytic cleavage. The oxidized hPTH(1–84) sample shows TIC-peaks at 18–20 min and several mass peaks due to mass shifts caused by oxidations. No significant signal for oxidized hPTH(1–84) species after removal of oxidized PTH molecules by a specific column with monoclonal antibodies (MAB) raised against the oxidized hPTH was detectable. By using this column in samples from 18 patients on dialysis we could demonstrate that measured PTH concentrations were substantially lower when considering oxidized forms of PTH. The relationship between PTH concentrations determined directly and those concentrations measured after removal of the oxidized PTH forms varies substantially. In some patients only 7% of traditionally measured PTH was free of oxidation, whereas in other patients 34% of the traditionally measured PTH was real intact PTH. In conclusion, a huge but not constant proportion of PTH molecules are oxidized in patients requiring dialysis. Since oxidized PTH is biologically inactive, the currently used methods to detect PTH in daily clinical practice may not adequately reflect PTH-related bone and cardiovascular abnormalities in patients on dialysis. PMID:22792251

  11. Tumour-associated fibroblasts contribute to neoangiogenesis in human parathyroid neoplasia.

    PubMed

    Verdelli, C; Avagliano, L; Creo, P; Guarnieri, V; Scillitani, A; Vicentini, L; Steffano, G B; Beretta, E; Soldati, L; Costa, E; Spada, A; Bulfamante, G P; Corbetta, S

    2015-02-01

    Components of the tumour microenvironment initiate and promote cancer development. In this study, we investigated the stromal component of parathyroid neoplasia. Immunohistochemistry for alpha-smooth muscle actin (?-SMA) showed an abundant periacinar distribution of ?-SMA(+) cells in normal parathyroid glands (n=3). This pattern was progressively lost in parathyroid adenomas (PAds; n=6) where ?-SMA(+)cells were found to surround new microvessels, as observed in foetal parathyroid glands (n=2). Moreover, in atypical adenomas (n=5) and carcinomas (n=4), ?-SMA(+) cells disappeared from the parenchyma and accumulated in the capsula and fibrous bands. At variance with normal glands, parathyroid tumours (n=37) expressed high levels of fibroblast-activation protein (FAP) transcripts, a marker of tumour-associated fibroblasts. We analysed the ability of PAd-derived cells to activate fibroblasts using human bone-marrow mesenchymal stem cells (hBM-MSCs). PAd-derived cells induced a significant increase in FAP and vascular endothelial growth factor A (VEGFA) mRNA levels in co-cultured hBM-MSCs. Furthermore, the role of the calcium-sensing receptor (CASR) and of the CXCL12/CXCR4 pathway in the PAd-induced activation of hBM-MSCs was investigated. Treatment of co-cultures of hBM-MSCs and PAd-derived cells with the CXCR4 inhibitor AMD3100 reduced the stimulated VEGFA levels, while CASR activation by the R568 agonist was ineffective. PAd-derived cells co-expressing parathyroid hormone (PTH)/CXCR4 and PTH/CXCL12 were identified by FACS, suggesting a paracrine/autocrine signalling. Finally, CXCR4 blockade by AMD3100 reduced PTH gene expression levels in PAd-derived cells. In conclusion, i) PAd-derived cells activated cells of mesenchymal origin; ii) PAd-associated fibroblasts were involved in tumuor neoangiogenesis and iii) CXCL12/CXCR4 pathway was expressed and active in PAd cells, likely contributing to parathyroid tumour neoangiogenesis and PTH synthesis modulation. PMID:25515730

  12. Short-term effects of high-dose oral vitamin D3 in critically ill vitamin D deficient patients: a randomized, double-blind, placebo-controlled pilot study

    PubMed Central

    2011-01-01

    Introduction Vitamin D deficiency is encountered frequently in critically ill patients and might be harmful. Current nutrition guidelines recommend very low vitamin D doses. The objective of this trial was to evaluate the safety and efficacy of a single oral high-dose vitamin D3 supplementation in an intensive care setting over a one-week observation period. Methods This was a randomized, double-blind, placebo-controlled pilot study in a medical ICU at a tertiary care university center in Graz, Austria. Twenty-five patients (mean age 62 ± 16yrs) with vitamin D deficiency [25-hydroxyvitamin D (25(OH)D) ?20 ng/ml] and an expected stay in the ICU >48 hours were included and randomly received either 540,000 IU (corresponding to 13.5 mg) of cholecalciferol (VITD) dissolved in 45 ml herbal oil or matched placebo (PBO) orally or via feeding tube. Results The mean serum 25(OH)D increase in the intervention group was 25 ng/ml (range 1-47 ng/ml). The highest 25(OH)D level reached was 64 ng/ml, while two patients showed a small (7 ng/ml) or no response (1 ng/ml). Hypercalcemia or hypercalciuria did not occur in any patient. From day 0 to day 7, total serum calcium levels increased by 0.10 (PBO) and 0.15 mmol/L (VITD; P < 0.05 for both), while ionized calcium levels increased by 0.11 (PBO) and 0.05 mmol/L (VITD; P < 0.05 for both). Parathyroid hormone levels decreased by 19 and 28 pg/ml (PBO and VITD, ns) over the seven days, while 1,25(OH)D showed a transient significant increase in the VITD group only. Conclusions This pilot study shows that a single oral ultra-high dose of cholecalciferol corrects vitamin D deficiency within 2 days in most patients without causing adverse effects like hypercalcemia or hypercalciuria. Further research is needed to confirm our results and establish whether vitamin D supplementation can affect the clinical outcome of vitamin D deficient critically ill patients. EudraCT Number 2009-012080-34 German Clinical Trials Register (DRKS) DRKS00000750 PMID:21443793

  13. Combination treatment with progesterone and vitamin D hormone is more effective than monotherapy in ischemic stroke: the role of BDNF/TrkB/Erk1/2 signaling in neuroprotection.

    PubMed

    Atif, Fahim; Yousuf, Seema; Sayeed, Iqbal; Ishrat, Tauheed; Hua, Fang; Stein, Donald G

    2013-04-01

    We investigated whether combinatorial post-injury treatment with progesterone (P4) and vitamin D hormone (VDH) would reduce ischemic injury more effectively than P4 alone in an oxygen glucose deprivation (OGD) model in primary cortical neurons and in a transient middle cerebral artery occlusion (tMCAO) model in rats. In the OGD model, P4 and VDH each showed neuroprotection individually, but combination of the "best" doses did not show substantial efficacy; instead, the lower dose of VDH in combination with P4 was the most effective. In the tMCAO model, P4 and VDH were given alone or in combination at different times post-occlusion for 7 days. In vivo data confirmed the in vitro findings and showed better infarct reduction at day 7 and functional outcomes (at 3, 5 and 7 days post-occlusion) after combinatorial treatment than when either agent was given alone. VDH, but not P4, upregulated heme oxygenase-1, suggesting a pathway for the neuroprotective effects of VDH differing from that of P4. The combination of P4 and VDH activated brain-derived neurotrophic factor and its specific receptor, tyrosine kinase receptor-B. Under specific conditions VDH potentiates P4's neuroprotective efficacy and should be considered as a potential partner of P4 in a low-cost, safe and effective combinatorial treatment for stroke. PMID:23154302

  14. Vitamin D

    PubMed Central

    Gröber, Uwe; Spitz, Jörg; Reichrath, Jörg; Kisters, Klaus; Holick, Michael F

    2013-01-01

    Vitamin D has received a lot of attention recently as a result of a meteoric rise in the number of publications showing that vitamin D plays a crucial role in a plethora of physiological functions and associating vitamin D deficiency with many acute and chronic illnesses including disorders of calcium metabolism, autoimmune diseases, some cancers, type 2 diabetes mellitus, infectious diseases and cardiovascular disease. The recent data on vitamin D from experimental, ecological, case-control, retrospective and prospective observational studies, as well as smaller intervention studies, are significant and confirm the sunshine vitamin’s essential role in a variety of physiological and preventative functions. The results of these studies justify the recommendation to improve the general vitamin D status in children and adults by means of a healthy approach to sunlight exposure, consumption of foods containing vitamin D and supplementation with vitamin D preparations. In general, closer attention should therefore be paid to vitamin D deficiency in medical and pharmaceutical practice than has been the case hitherto. PMID:24516687

  15. Article de synthse Le peptide apparent l'hormone

    E-print Network

    Boyer, Edmond

    , le colostrum et le lait pourrait également lui conférer un rôle physiologique important dans la-né. calcium / foetus / placenta / mamelle / colostrum / nouveau-né Summary ― Parathyroid hormone to its foetus. PTHrP, which is also present in the mammary gland, colostrum and milk, mightplay

  16. Chemical and hormonal determinants of vascular calcification in vitro

    Microsoft Academic Search

    K Lomashvili; P Garg; W C O'Neill

    2006-01-01

    Vascular calcification is a complex process that is dependent not only on the physicochemical effects of Ca, PO4, and pH, but also on smooth muscle factors that may be regulated by these ions as well as by 1,25-dihydroxyvitamin D3 (calcitriol) and parathyroid hormone (PTH). These minerals and hormones were tested in a model of medial calcification in rat aorta maintained

  17. Mouse and Human BAC Transgenes Recapitulate Tissue-Specific Expression of the Vitamin D Receptor in Mice and Rescue the VDR-Null Phenotype

    PubMed Central

    Lee, Seong Min; Bishop, Kathleen A.; Goellner, Joseph J.; O'Brien, Charles A.

    2014-01-01

    The biological actions of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) are mediated by the vitamin D receptor (VDR), which is expressed in numerous target tissues in a cell type-selective manner. Recent studies using genomic analyses and recombineered bacterial artificial chromosomes (BACs) have defined the specific features of mouse and human VDR gene loci in vitro. In the current study, we introduced recombineered mouse and human VDR BACs as transgenes into mice and explored their expression capabilities in vivo. Individual transgenic mouse strains selectively expressed BAC-derived mouse or human VDR proteins in appropriate vitamin D target tissues, thereby recapitulating the tissue-specific expression of endogenous mouse VDR. The mouse VDR transgene was also regulated by 1,25(OH)2D3 and dibutyryl-cAMP. When crossed into a VDR-null mouse background, both transgenes restored wild-type basal as well as 1,25(OH)2D3-inducible gene expression patterns in the appropriate tissues. This maneuver resulted in the complete rescue of the aberrant phenotype noted in the VDR-null mouse, including systemic features associated with altered calcium and phosphorus homeostasis and disrupted production of parathyroid hormone and fibroblast growth factor 23, and abnormalities associated with the skeleton, kidney, parathyroid gland, and the skin. This study suggests that both mouse and human VDR transgenes are capable of recapitulating basal and regulated expression of the VDR in the appropriate mouse tissues and restore 1,25(OH)2D3 function. These results provide a baseline for further dissection of mechanisms integral to mouse and human VDR gene expression and offer the potential to explore the consequence of selective mutations in VDR proteins in vivo. PMID:24693968

  18. [Vitamin C].

    PubMed

    Fain, Olivier

    2013-10-01

    Vitamin C is a water soluble vitamin which is mainly fresh fruits and vegetables foodborne. Vitamin C deficiency is most often due to a lack of daily amount. Scurvy is characterized by the occurrence of fatigue, myalgia, arthralgia, purpura, bleeding disorders, and later by dental manifestations. Biological signs are nonspecific: anemia, hypocholesterolemia, hypoalbuminemia. Clinical suspicion is confirmed by the decrease in ascorbic acid level (< 2 mg/L). It must be interpreted in light of the acute phase reactants. The treatment is the administration of 1 g of vitamin C per day for 15 days. Vitamin C depletion (ascorbic acid: 2 to 5 mg/L) could induce long-term complications. The recommended dietary allowance of vitamin C protect from these risks. PMID:24298827

  19. Mexico City normal weight children exposed to high concentrations of ambient PM2.5 show high blood leptin and endothelin-1, vitamin D deficiency, and food reward hormone dysregulation versus low pollution controls. Relevance for obesity and Alzheimer disease.

    PubMed

    Calderón-Garcidueńas, Lilian; Franco-Lira, Maricela; D'Angiulli, Amedeo; Rodríguez-Díaz, Joel; Blaurock-Busch, Eleonore; Busch, Yvette; Chao, Chih-Kai; Thompson, Charles; Mukherjee, Partha S; Torres-Jardón, Ricardo; Perry, George

    2015-07-01

    Millions of Mexico, US and across the world children are overweight and obese. Exposure to fossil-fuel combustion sources increases the risk for obesity and diabetes, while long-term exposure to fine particulate matter (PM2.5) and ozone (O3) above US EPA standards is associated with increased risk of Alzheimer's disease (AD). Mexico City Metropolitan Area children are chronically exposed to PM2.5 and O3 concentrations above the standards and exhibit systemic, brain and intrathecal inflammation, cognitive deficits, and Alzheimer disease neuropathology. We investigated adipokines, food reward hormones, endothelial dysfunction, vitamin D and apolipoprotein E (APOE) relationships in 80 healthy, normal weight 11.1±3.2 year olds matched by age, gender, BMI and SES, low (n: 26) versus high (n:54) PM2.5 exposures. Mexico City children had higher leptin and endothelin-1 (p<0.01 and p<0.000), and decreases in glucagon-like peptide-1 (GLP 1), ghrelin, and glucagon (<0.02) versus controls. BMI and leptin relationships were significantly different in low versus high PM2.5 exposed children. Mexico City APOE 4 versus 3 children had higher glucose (p=0.009). Serum 25-hydroxyvitamin D<30ng/mL was documented in 87% of Mexico City children. Leptin is strongly positively associated to PM 2.5 cumulative exposures. Residing in a high PM2.5 and O3 environment is associated with 12h fasting hyperleptinemia, altered appetite-regulating peptides, vitamin D deficiency, and increases in ET-1 in clinically healthy children. These changes could signal the future trajectory of urban children towards the development of insulin resistance, obesity, type II diabetes, premature cardiovascular disease, addiction-like behavior, cognitive impairment and Alzheimer's disease. Increased efforts should be made to decrease pediatric PM2.5 exposures, to deliver health interventions prior to the development of obesity and to identify and mitigate environmental factors influencing obesity and Alzheimer disease. PMID:26037109

  20. Vitamin D binding protein genotype is associated with plasma 25OHD concentration in West African children.

    PubMed

    Braithwaite, V S; Jones, K S; Schoenmakers, I; Silver, M; Prentice, A; Hennig, B J

    2015-05-01

    Vitamin D is well known for its role in promoting skeletal health. Vitamin D status is determined conventionally by circulating 25-dihydroxyvitamin D (25OHD) concentration. There is evidence indicating that circulating 25OHD concentration is affected by variation in Gc, the gene encoding the vitamin D binding protein (DBP). The composite genotype of two single nucleotide polymorphisms (rs7041 and rs4588) results in different DBP isotypes (Gc1f, Gc1s and Gc2). The protein configurational differences among DBP isotypes affect DBP substrate binding affinity. The aims of this study were to determine 1) Gc variant frequencies in a population from an isolated rural region of The Gambia, West Africa (n=3129) with year-round opportunity for cutaneous vitamin D synthesis and 2) the effects of Gc variants on 25OHD concentration (n=237) in a genetically representative sub-group of children (mean (SD) age: 11.9 (4.8) years). The distribution of Gc variants was Gc1f: 0.86, Gc1s: 0.11 and Gc2: 0.03. The mean (SD) concentration of 25OHD was 59.6 (12.9) nmol/L and was significantly higher in those homozygous for Gc1f compared to other Gc variants (60.7 (13.1) vs. 56.6 (12.1) nmol/L, P=0.03). Plasma 25OHD and 1,25(OH)2D concentration was significantly associated with parathyroid hormone in Gc1f-1f but not in the other Gc variants combined. This study demonstrates that different Gc variants are associated with different 25OHD concentrations in a rural Gambian population. Gc1f-1f, thought to have the highest affinity for 25OHD, had the highest 25OHD concentration compared with lower affinity Gc variants. The considerable difference in Gc1f frequency observed in Gambians compared with other non-West African populations and associated differences in plasma 25OHD concentration, may have implications for the way in which vitamin D status should be interpreted across different ancestral groups. PMID:25652210

  1. Physiology of Calcium and Phosphate Metabolism: 1980 Refresher Course, Syllabus.

    ERIC Educational Resources Information Center

    Knox, Franklyn G., Ed.

    1980-01-01

    This syllabus reviews information concerning calcium and phosphate regulation. Topics of interest include the following: calcium metabolism, phosphorus metabolism, bone, parathyroid hormone, calcitonin, and vitamin D. (CS)

  2. A quantitative ultrastructural study of microtubule content and secretory granule accumulation in parathyroid glands of phosphate- and colchicine-treated rats.

    PubMed Central

    Reaven, E P; Reaven, G M

    1975-01-01

    Microtubule involvement in secretory events of the parathyroid gland was investigated in rats treated with colchicine and/or phosphorus, agents which have been shown to modify parathyroid secretion. Quantitative ultrastructural techniques were used in an effort to assess the cytoplasmic microtubule and secretory granule content of chief cells 3 h after treatment, when hypocalcemia was well established. After cochicine administration, the chief cells appeared to have lost all assembled microtubules and accumulated greater than normal amounts of cytoplasmic secretory granules. On the other hand, phosphorus treatment was associated with increased microtubule content although the cytoplasmic content of secretory granules remained unchanged. When colchicine and phosphorus were given concomitantly, microtubules were again absent, but the secretory granule content of the cells was markedly increased. These data provide direct evidence that colchicine disrupts assembled microtubules in chief cells of rat parathyroids; the consequence of this effect appears to be a blockage of hormone release which is reflected in the accumulation of secretory granules in the cell. The fact that microtubules also show a significant increase in content when hormone release from chief cells is presumed to increase, suggests that microtubules may participate in the physiological control of parathyroid hormone secretion. Images PMID:1141440

  3. Vitamin A

    MedlinePLUS

    ... vitamin A to decrease the risk of transmitting HIV to the baby during pregnancy, childbirth, or breast-feeding. Men use vitamin A ... mouth does not lower the risk of passing HIV to the fetus during pregnancy, to newborns during delivery, or to infants during ...

  4. B Vitamins

    MedlinePLUS

    The B vitamins are B1 (thiamine) B2 (riboflavin) B3 (niacin) B5 (pantothenic acid) B6 B7 (biotin) B12 Folic acid These ... help form red blood cells. You can get B vitamins from proteins such as fish, poultry, meat, eggs, ...

  5. Vitamin K

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin K was identified in the early 1930’s when it was shown to be essential for normal blood coagulation. Phylloquinone (2-methyl-3-phytyl-1,4-naphthoquinone) found in green plants is the major source of the vitamin. Large amounts of menaquinones with lengthy side chains are also synthesized in...

  6. Intravenous Ketoprofen in Thyroid and Parathyroid Surgery

    Microsoft Academic Search

    Emmanuel R. Basto; Catherine Waintrop; Benoît G. Eurin; Laurent P. Jacob

    2001-01-01

    We compared the ketoprofen-propacetamol combination relative to propacetamol alone in thyroid and parathyroid surgery in terms of postoperative analgesic efficacy, bleeding, and incidence of nausea and vomiting to deter- mine whether ketoprofen results in any benefit in this type of surgery. Patients were distributed in two parallel groups to be managed by anesthesiologists habitually prescribing (Ketoprofen group) or not prescribing

  7. The blood supply of mediastinal parathyroid adenomas.

    PubMed

    Doppman, J L; Marx, S J; Brennan, M F; Beazley, R M; Geelhoed, G; Aurbach, G D

    1977-04-01

    Arteriography for parathyroid localization following unsuccessful neck surgery should include selective catheterization of the inferior thyroid and internal mammary arteries bilaterally. When the arterial supply to a mediastinal adenoma arises from the internal mammary artery, recovery from the neck may not be possible and an open mediastinal exploration (or embolization) should be considered. PMID:843142

  8. Suppression of parathyroid gland activity by magnesium

    Microsoft Academic Search

    E. Altenähr; F. Leonhardt

    1972-01-01

    Hypocalcaemia (and hypophosphataemia) with significant activation of parathyroid glands (PTG) in rats is produced by a calcium and phosphate deficient diet. During administration of a 0.1 M solution of calcium gluconate as drinking water, plasma calcium levels remain within normal limits; administration of 0.1 M magnesium aspartate results in hypermagnesaemia in addition to the hypocalcaemia. The activation of PTGs is

  9. Is vitamin D a determinant of muscle mass and strength?

    PubMed

    Marantes, Isabel; Achenbach, Sara J; Atkinson, Elizabeth J; Khosla, Sundeep; Melton, L Joseph; Amin, Shreyasee

    2011-12-01

    There remains little consensus on the link between vitamin levels and muscle mass or strength. We therefore investigated the association of serum 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)(2) D), and parathyroid hormone (PTH) levels with skeletal muscle mass and strength. We studied 311 men (mean age, 56 years; range, 23-91 years) and 356 women (mean age, 57 years; range, 21-97 years) representing an age-stratified, random sample of community adults. Multivariate linear regression models were used to examine the association of skeletal muscle mass (by total body dual-energy X-ray absorptiometry) and strength (handgrip force and isometric knee extension moment) with each of 25(OH)D, 1,25(OH)(2) D, and PTH quartiles, adjusted for age, physical activity, fat mass, and season. We found no consistent association between 25(OH)D or PTH and any of our measurements of muscle mass or strength, in either men or women. However, in subjects younger than 65 years, there was a statistically significant association between low 1,25(OH)(2) D levels and low skeletal mass in both men and women and low isometric knee extension moment in women, after adjustment for potential confounders. Modestly low 25(OH)D or high PTH levels may not contribute significantly to sarcopenia or muscle weakness in community adults. The link between low 25(OH)D and increased fall risk reported by others may be due to factors that affect neuromuscular function rather than muscle strength. The association between low 1,25(OH)(2) D and low skeletal mass and low knee extension moment, particularly in younger people, needs further exploration. PMID:21915904

  10. Is Vitamin D a Determinant of Muscle Mass and Strength?

    PubMed Central

    Marantes, Isabel; Achenbach, Sara J.; Atkinson, Elizabeth J.; Khosla, Sundeep; Melton, L. Joseph; Amin, Shreyasee

    2011-01-01

    Background There remains little consensus on the link between vitamin D levels and muscle mass or strength. We therefore investigated the association of serum 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and parathyroid hormone (PTH) levels with skeletal muscle mass and strength. Methods We studied 311 men (mean age, 56 yrs; range, 23-91 yrs) and 356 women (mean age, 57 yrs; range, 21-97 yrs) representing an age-stratified, random sample of community adults. Multivariate linear regression models were used to examine the association of skeletal muscle mass (by total body dual-energy x-ray absorptiometry) and strength (handgrip force and isometric knee extension moment) with each of 25(OH)D, 1,25(OH)2D and PTH quartiles, adjusted for age, physical activity, fat mass and season. Results We found no consistent association between 25(OH)D or PTH and any of our measurements of muscle mass or strength, in either men or women. However, in subjects younger than 65 years, there was a statistically significant association between low 1,25(OH)2D levels and low skeletal mass in both men and women and low isometric knee extension moment in women, after adjustment for potential confounders. Conclusion Modestly low 25(OH)D or high PTH levels may not contribute significantly to sarcopenia or muscle weakness in community adults. The link between low 25(OH)D and increased fall risk reported by others may be due to factors that affect neuromuscular function rather than muscle strength. The association between low 1,25(OH)2D and low skeletal mass and low knee extension moment, particularly in younger people, needs further exploration. PMID:21915904

  11. Metabolic studies in congenital vitamin D deficiency rickets.

    PubMed

    Teotia, M; Teotia, S P; Nath, M

    1995-01-01

    Congenital rickets in 3 newborns of mothers with advanced nutritional osteomalacia, healed with maternal breast milk feeding when mothers alone were given calcium supplements and 7.5 mg of intravenous D2 and the mother baby pair protected from sunlight. Maternal plasma biochemistry indicated more severe vitamin D deficiency compared to their newborns (intrauterine foetal priority). The first dose of 7.5 mg of vitamin D3 and calcium supplements to mother healed osteomalacia but did not appear to heal the rickets of their breast fed infants (extrauterine maternal priority for vitamin D). A second dose given at 3 months interval healed the rickets in their infants and the biochemistry of the mother and baby returned towards normal. Congenital rickets developed when maternal bone mineral and vitamin D stores had been completely exhausted. Raised IPTH levels in the newborn suggested that foetal parathyroids were responsive to hypocalcaemic stimulus. PMID:10829844

  12. Vitamin D status is associated with bone mineral density and bone mineral content in preschool-aged children.

    PubMed

    Hazell, Tom J; Pham, Thu Trang; Jean-Philippe, Sonia; Finch, Sarah L; El Hayek, Jessy; Vanstone, Catherine A; Agellon, Sherry; Rodd, Celia J; Weiler, Hope A

    2015-01-01

    This study examined the associations between vitamin D status, bone mineral content (BMC), areal bone mineral density (aBMD), and markers of calcium homeostasis in preschool-aged children. Children (n=488; age range: 1.8-6.0 y) were randomly recruited from Montreal. The distal forearm was scanned using a peripheral dual-energy X-ray absorptiometry scanner (Lunar PIXI; GE Healthcare, Fairfield, CT). A subset (n=81) had clinical dual-energy X-ray absorptiometry (cDXA) scans (Hologic 4500A Discovery Series) of lumbar spine (LS) 1-4, whole body, and ultradistal forearm. All were assessed for plasma 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone concentrations (Liaison; Diasorin), ionized calcium (ABL80 FLEX; Radiometer Medical A/S), and dietary vitamin D and calcium intakes by survey. Age (p<0.001) and weight-for-age Z-score (p<0.001) were positively associated with BMC and aBMD in all regression models, whereas male sex contributed positively to forearm BMC and aBMD. Having a 25(OH)D concentration of >75 nmol/L positively associated with forearm and whole body BMC and aBMD (p<0.036). Sun index related to (p<0.029) cDXA forearm and LS 1-4 BMC and whole-body aBMD. Nutrient intakes did not relate to BMC or aBMD. In conclusion, higher vitamin D status is linked to higher BMC and aBMD of forearm and whole body in preschool-aged children. PMID:24880497

  13. The serum 24,25-dihydroxyvitamin D concentration, a marker of vitamin D catabolism, is reduced in chronic kidney disease

    PubMed Central

    Bosworth, Cortney; Levin, Gregory; Robinson-Cohen, Cassianne; Hoofnagle, Andrew N.; Ruzinski, John; Young, Bessie; Schwartz, Stephen; Himmelfarb, Jonathan; Kestenbaum, Bryan; de Boer, Ian H.

    2012-01-01

    Chronic kidney disease is characterized, in part, as a state of decreased production of 1,25-dihydroxyvitamin D (1,25(OH)2D); however, this paradigm overlooks the role of vitamin D catabolism. We developed a mass spectrometric assay to quantify serum concentration of 24,25-dihydroxyvitamin D (24,25(OH)2D), the first metabolic product of 25-hydroxyvitamin D (25(OH)D) by CYP24A1, and determined its clinical correlates and associated outcomes among 278 participants with chronic kidney disease in the Seattle Kidney Study. For eGFRs of 60 or more, 45–59, 30–44, 15–29, and under 15 ml/min/1.73m2, the mean serum 24,25(OH)2D concentrations significantly trended lower from 3.6, 3.2, 2.6, 2.6, to 1.7 ng/ml, respectively. Non-Hispanic Black race, diabetes, albuminuria, and lower serum bicarbonate were also independently and significantly associated with lower 24,25(OH)2D concentrations. The 24,25(OH)2D concentration was more strongly correlated with that of parathyroid hormone than was 25(OH)D or 1,25(OH)2D. A 24,25(OH)2D concentration below the median was associated with increased risk of mortality in unadjusted analysis, but this was attenuated with adjustment for potential confounding variables. Thus, chronic kidney disease is a state of stagnant vitamin D metabolism characterized by decreases in both 1,25(OH)2D production and vitamin D catabolism. PMID:22648296

  14. The pleiotropic actions of vitamin D

    Microsoft Academic Search

    Roberto Lin; John H. White

    2004-01-01

    Summary General knowledge of the role of vitamin D3 in human physiology has been shaped by its discovery as a pre- ventive agent of nutritional rickets, a defect in bone development due to inadequate uptake of dietary cal- cium. Studies on the function of the hormonal form of vitamin D3 ,1 a,25-dihydroxyvitamin D3, have been greatly accelerated by the molecular

  15. Genetic influences on bone density: Physiological correlates of vitamin D receptor gene alleles in premonopausal women

    SciTech Connect

    Howard, G.; Nguyen, T.; Morrison, N. [St. Vincent`s Hospital, Sydney, New South Wales (Australia)] [and others] [St. Vincent`s Hospital, Sydney, New South Wales (Australia); and others

    1995-09-01

    Common vitamin D receptor (VDR) gene alleles have recently been shown to contribute to the genetic variability in bone mass and bone turnover; however, the physiological mechanisms involved are unknown. To examine this, the response to 7 days of 2 {mu}g oral 1,25-dihydroxyvitamin D[1,25-(OH){sub 2}D] (calcitrol) stimulation was assessed in 21 premenopausal women, homozygous for one or other of the common VDR alleles (bb, N = 11; BB, n = 10). Indices of bone turnover and calcium homeostasis were measured during 2 weeks. Baseline osteocalcin, 1,25-(OH){sub 2}D, type I collagen carboxyterminal telopeptide, and inorganic phosphate levels were significantly higher and spinal bone mineral density was significantly lower in the BB allelic group. After calcitrol administration, similar levels of 1,25-(OH){sub 2}D were attained throughout the study in both genotypic groups. The increase in serum osteocalcin levels in the BB group was significantly less than that in the bb group (11% vs. 32%, P = 0.01). The genotype-related baseline difference in osteocalcin levels was not apparent at the similar serum 1,25-(OH){sub 2}D levels. By contrast, the baseline differences in phosphate and type I collagen carboxyterminal telopeptide persisted throughout the study. Serum ionized calcium levels did not differ between genotypes, nor did it move out of normal range values. However, parathyroid hormone was less suppressed in the low bone density group (38% vs. 11%, P = 0.01). These data indicate that the VDR alleles are associated with differences in the vitamin D endocrine system and may have important implications in relation to the pathophysiology of osteoporosis. 35 refs., 2 figs., 1 tab.

  16. Vitamin D

    MedlinePLUS

    Vitamin D helps the body absorb calcium . Calcium and phosphate are two minerals that are essential for normal bone formation. Throughout childhood, your body uses these minerals to produce bones. If you do ...

  17. Vitamin A

    MedlinePLUS

    ... also known as retinol because it produces the pigments in the retina of the eye. Vitamin A ... some fortified foods. Carotenoids are dark-colored dyes (pigments) found in plant foods that can turn into ...

  18. Vitamin E

    MedlinePLUS

    ... Vitamin E is found in the following foods: Vegetable oils (such as wheat germ, sunflower, safflower, corn, and soybean oils) Nuts (such as almonds, peanuts, and hazelnuts/filberts) ... (such as spinach and broccoli) Fortified breakfast cereals, ...

  19. Vitamin D

    MedlinePLUS

    ... for Parents for Kids for Teens Teens Home Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Q&A School & Jobs Drugs & Alcohol Staying Safe Recipes En Espańol ... Body Image Vitamin D KidsHealth > Teens > Food & Fitness > Nutrition ...

  20. Behavioural anomalies in mice evoked by ``Tokyo'' disruption of the Vitamin D receptor gene

    E-print Network

    Kalueff, Allan V.

    Behavioural anomalies in mice evoked by ``Tokyo'' disruption of the Vitamin D receptor gene Allan V December 2005 Available online 19 January 2006 Abstract Vitamin D is a steroid hormone with many important functions in the brain, mediated through the nuclear Vitamin D receptor (VDR). Mounting clinical data link