These are representative sample records from Science.gov related to your search topic.
For comprehensive and current results, perform a real-time search at Science.gov.
1

Parathyroid Hormone, Calcitonin, and Vitamin D  

NASA Technical Reports Server (NTRS)

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

Potts, J. T.

1972-01-01

2

Vitamin D metabolites and bioactive parathyroid hormone levels during Spacelab 2  

NASA Technical Reports Server (NTRS)

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

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

1988-01-01

3

Serum Vitamin D, Parathyroid Hormone Levels, and Carotid Atherosclerosis  

PubMed Central

Evidence suggests low vitamin D and elevated parathyroid hormone (PTH) concentrations may increase risk for cardiovascular disease. However, little is known about the association between vitamin D or PTH and subclinical atherosclerosis. This cross-sectional study included 654 community-dwelling older adults aged 55–96 years (mean age, 75.5 years) without a history of coronary heart disease, revascularization, or stroke enrolled in the Rancho Bernardo Study who completed a clinic examination in 1997–1999 and provided a blood sample for determination of serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], and PTH concentrations. Carotid artery intima-media wall thickness (IMT) was measured as an indicator of atherosclerosis at two sites with B-mode ultrasound. After adjusting for age, sex, smoking, alcohol intake, waist-to-hip ratio, exercise, season of blood draw, diabetes, and hypertension, geometric mean internal carotid IMT (ptrend 0.022), but not common carotid IMT (ptrend 0.834) decreased in a dose-dependent fashion with increasing concentration of 25(OH)D. There was no association of 1,25(OH)2D or PTH with either measure of carotid IMT. In subgroup analyses, 1,25(OH)2D was inversely associated with internal carotid IMT among those with hypertension (p for interaction 0.036). These findings from a population-based cohort of older adults suggest a potential role for vitamin D in the development of subclinical atherosclerosis. Additional research is needed to determine whether vitamin D may influence the progression of atherosclerosis, including the effects of supplementation on the atherosclerotic process. PMID:19539290

Reis, Jared P.; von Mühlen, Denise; Michos, Erin D.; R. Miller, Edgar; Appel, Lawrence J.; Araneta, Maria R.; Barrett-Connor, Elizabeth

2009-01-01

4

Vitamin D status and parathyroid hormone in obese children before and after weight loss  

Microsoft Academic Search

Objective: The roles of vitamin D and parathyroid hormone (PTH) are discussed controversially in obesity, and studies of these hormones in obese children are limited. Therefore, we studied the relationships between PTH, 1,25-dihydroxy-vitamin D (1,25-OH Vit D), 25-hydroxy-vitamin D (25-OH Vit D), weight status, and insulin sensitivity before and after weight loss in obese children. Methods: Fasting serum PTH, 1,25-OH

Thomas Reinehr; Gideon de Sousa; Ute Alexy; M Kersting; Werner Andler

2007-01-01

5

The control of calcium metabolism by parathyroid hormone, calcitonin and vitamin D  

NASA Technical Reports Server (NTRS)

Advances in analysis of chemistry and physiology of parathyroid hormone, calcitonin, and Vitamin D are described along with development of techniques in radioassay methods. Emphasis is placed on assessment of normal and abnormal patterns of secretion of these hormones in specific relation to the physiological adaptations of weightlessness and space flight. Related diseases that involve perturbations in normal skeletal and calcium homeostasis are also considered.

Potts, J. T., Jr.

1976-01-01

6

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

Microsoft Academic Search

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

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

2007-01-01

7

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

NASA Technical Reports Server (NTRS)

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

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

1975-01-01

8

Vitamin D deficiency and parathyroid hormone levels following renal transplantation in children  

Microsoft Academic Search

The objectives were to determine the prevalence of vitamin D deficiency [25(OH)D?parathyroid hormone (iPTH)\\u000a levels following transplantation. Serum 25(OH)D, 1,25(OH)2D, and iPTH were measured once in 275 healthy controls and at transplantation, and 3 and 12 months posttransplantation in\\u000a 58 RTx recipients.

Shamir Tuchman; Heidi J. Kalkwarf; Babette S. Zemel; Justine Shults; Rachel J. Wetzsteon; Debbie Foerster; C. Frederic Strife; Mary B. Leonard

2010-01-01

9

Vitamin D, parathyroid hormone levels and bone mineral density in community-dwelling older women: The Rancho Bernardo Study  

Microsoft Academic Search

Vitamin D (25(OH)D) increases the efficiency of intestinal calcium absorption. Low levels of serum calcium stimulate the secretion of parathyroid hormone (PTH), which maintains serum calcium levels at the expense of increased bone turnover, bone loss and increased risk of fractures. We studied the association between 25(OH)D and PTH levels, and their associations with bone mineral density (BMD), bone loss,

Denise G. von Mühlen; Gail A. Greendale; Cedric F. Garland; Lori Wan; Elizabeth Barrett-Connor

2005-01-01

10

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

Microsoft Academic Search

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

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

1993-01-01

11

Disturbances of parathyroid hormone–vitamin D axis in non-cholestatic chronic liver disease: a cross-sectional study  

Microsoft Academic Search

Purpose  Liver has an important role in metabolism of vitamin D. This study aimed to evaluate the patterns of vitamin D–parathyroid\\u000a hormone (PTH) disturbance and correlate it in patients with non-cholestatic chronic liver disease (CLD).\\u000a \\u000a \\u000a \\u000a \\u000a Methods  A total of 40 healthy controls and 90 consecutive patients with evidence of non-cholestatic CLD due to hepatitis C (n = 28), hepatitis B (n = 26), autoimmune hepatitis (n = 19),

Arash Miroliaee; Mohsen Nasiri-Toosi; Omid Khalilzadeh; Alireza Esteghamati; Alireza Abdollahi; Mehdi Mazloumi

2010-01-01

12

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

PubMed Central

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

Naveh-Many, T; Silver, J

1990-01-01

13

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

PubMed Central

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

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

14

Evidence of associations between feto-maternal vitamin D status, cord parathyroid hormone and bone-specific alkaline phosphatase, and newborn whole body bone mineral content  

Technology Transfer Automated Retrieval System (TEKTRAN)

In spite of a high prevalence of vitamin D inadequacy in pregnant women and neonates, relationships among vitamin D status [25(OH)D], parathyroid hormone (PTH), bone specific alkaline phosphatase (BALP), and whole body bone mineral content (WBBMC) in the newborn are poorly characterized. The purpose...

15

Vitamin D and parathyroid hormone status in a representative population living in Macau, China.  

PubMed

Associations between documented sun-exposure, exercise patterns and fish and supplement intake and 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) were investigated in a random household survey of Macau residents (aged 18-93). Blood samples (566) taken in summer were analyzed for 25OHD and PTH. In this Chinese population, 55% were deficient (25OHD <50nmol/L: median (interquartile range)=47.7 (24.2) nmol/L). Vitamin D deficiency was greatest in those aged <50 years: median (interquartile range)=43.3 (18.2) nmol/L, females: median (interquartile range)=45.5 (19.4) nmol/L and those with higher educational qualifications: median (interquartile range)=43.1 (18.7) nmol/L. In the total Macau population, statistically significant (p<0.01) modifiable associations with lower 25OHD levels were sunlight exposure (?=0.06), physical activity (PA) (measured as hours(hrs)/day: ?=0.08), sitting (measured as hrs/day ?=-0.20), intake of fish (?=0.08) and calcium (Ca) supplement intake (?=0.06) [linear regression analysis adjusting for demographic risk factors]. On similar analysis, and after adjustment for 25OHD, the only significant modifiable associations in the total population with PTH were sitting (?=-0.17), Body Mass Index (?=0.07) and Ca supplement intake (?=-0.06). In this Macau population less documented sun exposure, fish and Ca supplement intake and exercise were associated with lower 25OHD levels, especially in the younger population, along with the interesting finding that more sitting was associated with both lower 25OHD and high PTH blood levels. In conclusion, unlike findings from Caucasian populations, younger participants were significantly more vitamin D deficient, in particular highly educated single females. This may indicate the desire of young females to be pale and avoid the sun. There are also big differences in lifestyle between the older generation and the younger, in particular with respect to sun exposure and PA. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. PMID:25636721

Ke, L; Mason, R S; Mpofu, E; Dibley, M; Li, Y; Brock, K E

2015-04-01

16

Disturbances of parathyroid hormone–vitamin D axis in non-cholestatic chronic liver disease: a cross-sectional study  

PubMed Central

Purpose Liver has an important role in metabolism of vitamin D. This study aimed to evaluate the patterns of vitamin D–parathyroid hormone (PTH) disturbance and correlate it in patients with non-cholestatic chronic liver disease (CLD). Methods A total of 40 healthy controls and 90 consecutive patients with evidence of non-cholestatic CLD due to hepatitis C (n = 28), hepatitis B (n = 26), autoimmune hepatitis (n = 19), and cryptogenic causes (n = 17) were enrolled. Cirrhosis was evident in 51 patients. Serum concentrations of 25-hydroxy vitamin D, PTH, calcium, phosphate, and liver enzymes were measured. Child–Pugh classification was determined in cirrhotic patients. Results Vitamin D deficiency (<50 nmol/l) was found in 46 (51.1%) patients and vitamin D insufficiency (50–80 nmol/l) in 15 (16.7%) patients. Secondary hyperparathyroidism (serum PTH > 6.8 pmol/l) was present in 6 (6.7%) patients. The prevalence of vitamin D deficiency was significantly higher in cirrhotic versus noncirrhotic patients (76.5 vs. 17.9%; P < 0.001), whereas there was no significant difference in serum calcium, phosphate, and PTH levels. Child–Pugh class B and C patients had significantly lower vitamin D level compared with class A patients (P < 0.001), whereas there was no significant difference in serum calcium, phosphate, and PTH levels. No significant correlation was seen between vitamin D and PTH, calcium or phosphate levels. Lower serum level of vitamin D was associated with coagulopathy, hyperbilirubinemia, hypoalbuminemia, anemia, and thrombocytopenia. Conclusions Vitamin D inadequacy and the severity of liver dysfunction move in parallel in patients with non-cholestatic CLD. Vitamin D assessment and replacement should be considered in the management of patients with non-cholestatic CLD. PMID:21063488

Miroliaee, Arash; Nasiri-Toosi, Mohsen; Esteghamati, Alireza; Abdollahi, Alireza; Mazloumi, Mehdi

2010-01-01

17

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...

18

Aluminum, parathyroid hormone, and osteomalacia  

SciTech Connect

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

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

1983-01-01

19

Calcium, Parathyroid Hormone, and Vitamin D: Major Determinants of Chronic Pain in Hemodialysis Patients  

PubMed Central

Background and objectives: Pain is a frequent complaint of hemodialysis (HD) patients, yet information regarding its causes and frequency is relatively scarce. The aim of this study was to evaluate the frequency and possible causes of chronic pain in patients who are on long-term HD. Design, setting, participants, & measurements: We prospectively enrolled 100 patients who were undergoing maintenance HD for at least 3 mo. Pain was evaluated using the Brief Pain Inventory. Data collected on each participant included age, gender, ethnic origin, body mass index, smoking habits, time on dialysis, type of blood access, comorbidities, and biochemical and hematologic parameters. Results: The average age was 64.5 yr; the average time on dialysis 40.4 mo. Forty-five patients were male. Thirty-one participants were of Arabic origin. Fifty-three patients had diabetes, 36 of whom had diabetic retinopathy. Although 51 patients experienced chronic pain, only 19.6% described the pain as severe. Musculoskeletal pain, neuropathic pain, and headache were the most prevalent forms of pain. The presence of diabetic retinopathy and neuropathy (but not diabetes per se) and levels of intact parathyroid hormone, calcium, and calcitriol (but not 25-hydroxyvitamin D3) differed significantly between those who experienced chronic pain and those who did not. On a logistic regression model, higher serum calcium levels and intact parathyroid hormone levels >250 pg/ml were independently associated with chronic pain, as well as the presence of diabetic retinopathy. Calcitriol had a marginal effect. Conclusions: Disturbed mineral metabolism is strongly associated with chronic pain in long-term HD patients, along with microangiopathy. PMID:19578003

Haggiag, Isabelle; Os, Pnina; Bernheim, Jacques

2009-01-01

20

The Vitamin D, Ionised Calcium and Parathyroid Hormone Axis of Cerebral Capillary Function: Therapeutic Considerations for Vascular-Based Neurodegenerative Disorders  

PubMed Central

Blood-brain barrier dysfunction characterised by brain parenchymal extravasation of plasma proteins may contribute to risk of neurodegenerative disorders, however the mechanisms for increased capillary permeability are not understood. Increasing evidence suggests vitamin D confers central nervous system benefits and there is increasing demand for vitamin D supplementation. Vitamin D may influence the CNS via modulation of capillary function, however such effects may be indirect as it has a central role in maintaining calcium homeostasis, in concert with calcium regulatory hormones. This study utilised an integrated approach and investigated the effects of vitamin D supplementation, parathyroid tissue ablation (PTX), or exogenous infusion of parathyroid hormone (PTH) on cerebral capillary integrity. Parenchymal extravasation of immunoglobulin G (IgG) was used as a marker of cerebral capillary permeability. In C57BL/6J mice and Sprague Dawley rats, dietary vitamin D was associated with exaggerated abundance of IgG within cerebral cortex (CTX) and hippocampal formation (HPF). Vitamin D was also associated with increased plasma ionised calcium (iCa) and decreased PTH. A response to dose was suggested and parenchymal effects persisted for up to 24 weeks. Ablation of parathyroid glands increased CTX- and HPF-IgG abundance concomitant with a reduction in plasma iCa. With the provision of PTH, iCa levels increased, however the PTH treated animals did not show increased cerebral permeability. Vitamin D supplemented groups and rats with PTH-tissue ablation showed modestly increased parenchymal abundance of glial-fibrillary acidic protein (GFAP), a marker of astroglial activation. PTH infusion attenuated GFAP abundance. The findings suggest that vitamin D can compromise capillary integrity via a mechanism that is independent of calcium homeostasis. The effects of exogenous vitamin D supplementation on capillary function and in the context of prevention of vascular neurodegenerative conditions should be considered in the context of synergistic effects with calcium modulating hormones. PMID:25874538

Lam, Virginie; Takechi, Ryusuke; Pallabage-Gamarallage, Menuka; Giles, Corey; Mamo, John C. L.

2015-01-01

21

Acute Effects of Repetitive Hemodialysis on Circulating Immunoreactive Parathyroid Hormone Levels in Uremic Patients Undergoing Vitamin D (Calcitriol) Therapy  

Microsoft Academic Search

The acute effects on parathyroid gland activity of repetitive hemodialysis with a dialysate calcium concentration of between 3.5 and 4 mEq\\/l were evaluated in 21 hemodialysis patients on calcitriol therapy for 1 year or more. In this study circulating immunoreactive parathyroid hormone (iPTH) levels were measured using radioimmunoassay specific for C-terminal iPTH (C-PTH), middle molecule iPTH (MM-PTH) and intact iPTH

R. Bellazzi; D. Romanini; L. Bacchella; M. Nai; C. Aprile; M. Santagostino; A. De Vincenzi

1991-01-01

22

Renal adenylate cyclase and the interrelationship between parathyroid hormone and vitamin D in the regulation of urinary phosphate and adenosine cyclic 3',5'-monophosphate excretion.  

PubMed Central

This study examined the role of cyclic AMP in the phosphaturic response to parathyroid hormone in vitamin D-deficient rats. Infusion of purified bovine parathyroid hormone (13.3 mug/h) into control, D-fed, or D-deficient, thyroparathyroidectomized rats produced a sixfold increase in renal phosphate and cyclic AMP excretion in D-fed rats, but only a two- to threefold increase in both parameters in D-deficient animals. Intravenous injection of parathyroid hormone over the dosage range from 1-50 mug/kg resulted in a dose-dependent increase in phosphate and cyclic AMP excretion with both D-fed and D-deficient thyroparathyroidectomized rats. However, the D-deficient rats responded to these injections of parathyroid hormone with a two- to threefold increase in both renal phosphate and cyclic AMP excretion at the highest dose of 50 mug/kg, whereas the D-fed animals' response was 35-fold and 11-fold over control excretion levels of phosphate and cyclic AMP, respectively. To directly examine the role of the renal cortical adenylate cyclase system in the blunted phosphaturic and urinary cyclic AMP responses to parathyroid hormone in D-deficient rats, we prepared a plasma membrane fraction enriched in this enzyme activity from the renal cortex of D-fed and D-deficient thyroparathyroidectomized rats. The renal cortical adenylate cyclase of D-deficient rats showed significantly (P less than 0.001) less activation by parathyroid hormone over the hormone concentration range from 0.3 to 7.0 mug/ml than was observed with the enzyme prepared from D-fed animals. Basal adenylate cyclase activity and the fluoride-stimulated enzyme activity were not altered by the state of D-deficiency. These experiments demonstrate that the blunted phosphaturic response to parathyroid hormone observed in D-deficient rats is associated with the reduced responsiveness of the renal cortical adenylate cyclase to the hormone. Moreover, the defect in the renal membrane adenylate cyclase system appears to be localized at the level of PTH binding to membrane receptors or, alternatively, at the level of transmission of the hormone-receptor binding signal to the catalytic moiety of this membrane enzyme. Images PMID:175088

Forte, L R; Nickols, G A; Anast, C S

1976-01-01

23

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

PubMed Central

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

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

2012-01-01

24

Reduced Parathyroid Vitamin D Receptor Messenger Ribonucleic Acid Levels in Primary and Secondary Hyperparathyroidism  

Microsoft Academic Search

Vitamin D, via its receptor (VDR), inhibits the hormone secretion and proliferation of parathyroid cells. Vitamin D deficiency and re- duced parathyroid VDR expression has been associated with devel- opment of hyperparathyroidism (HPT) secondary to uremia. VDR polymorphisms may influence VDR messenger RNA (mRNA) levels and have been coupled to an increased risk of parathyroid adenoma of primary HPT. VDR

TOBIAS CARLING; JONAS RASTAD; EVA SZABO; GUNNAR WESTIN; GORAN ÅKERSTROM

25

Intraoperative Parathyroid Hormone Monitoring  

Microsoft Academic Search

The principles of minimally invasive parathyroidectomy include the successful preoperative localization of a solitary adenoma, a targeted operative approach that does not disturb the normal parathyroid glands, and intraoperative confirmation of excision of all hypersecreting parathyroid tissue. By providing real-time feedback to the surgical team, the rapid PTH assay allows surgeons to assess the completeness of parathyroid resection without visualizing

William B. Inabnet

2004-01-01

26

Effect of high parathyroid hormone level on bone mineral density in a vitamin D-sufficient population: Korea National Health and Nutrition Examination Survey 2008-2010.  

PubMed

The detrimental effect of high parathyroid hormone (PTH) on bone has not been adequately evaluated in vitamin D-sufficient Koreans. The aim of this study was to investigate the effect of high PTH on bone mineral density (BMD) in such a population. A total of 5,403 subjects (2,644 men and 2,759 postmenopausal women; ?50 years old) were selected from the 2008-2010 Korea National Health and Nutrition Examination Survey (KNHANES). Subjects were divided into four groups according to vitamin D status (<20 and ?20 ng/mL) and PTH levels (?65 and >65 pg/mL). Total hip and spine BMD were evaluated in each group. High PTH level was found in 50% of vitamin D-deficient subjects and 35% of vitamin D-sufficient subjects. In the vitamin D-deficient group, subjects with normal PTH level had higher total hip and spine BMD than those with high PTH after adjusting for multiple confounding factors, regardless of gender. In the vitamin D-sufficient group, only women with high PTH showed lower total hip and spine BMD than those with normal PTH. Multivariable linear regression analysis found that PTH level was independently associated with total hip BMD in vitamin D-sufficient women as well as vitamin D-insufficient women, but no association was found in men. In conclusion, high serum PTH level has an additive detrimental effect on BMD in postmenopausal women even though they had sufficient vitamin D levels. PMID:25242259

Kim, Se Hwa; Kim, Tae Ho; Kim, Soo-Kyung

2014-12-25

27

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

PubMed Central

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

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

2014-01-01

28

Parathyroid hormone response to vitamin D insufficiency in elderly males with chronic heart failure.  

PubMed

Secondary hyperparathyroidism (SHPT) may contribute to the systemic illness that accompanies chronic heart failure (CHF). Healthy elderly with vitamin D deficiency who did not develop hyperparathyroidism (functional hypoparathyroidism, FHPT) had lower mortality than those who did. This study was designed to examine determinants of the PTH response in the vitamin D insufficient CHF patients. Sixty five vitamin D insufficient males with NYHA class II and III and 20 control subjects age >/=55 years were recruited. Echocardiography, physical performance, NT-pro-BNP, PTH, 25-hydroxyvitamin D (25(OH)D), adiponectin and bone activity surrogate markers (OPG, RANKL, OC, beta-CTx) were assessed. Increased NYHA class was associated with SHPT, while physical performance was inferior compared to FHPT. SHPT was associated with lower left ventricular ejection fraction (LVEF) and flow mediated dilatation, but with higher left heart dimensions, left ventricular mass index and right ventricular systolic pressure. CHF patients with SHPT had increased NT-pro-BNP, adiponectin and bone markers, but decreased 25(OH)D compared to those with FHPT. Independent determinants for SHPT in CHF patients with vitamin D insufficiency were LVEF, adiponectin and beta-CTx, irrespective of renal function and serum vitamin D levels. In conclusion, increased PTH levels, but not low vitamin D, demonstrated close relation to CHF severity. PMID:21777017

Bozic, B; Loncar, G; Prodanovic, N; Lepic, T; Radojicic, Z; Cvorovic, V; Dimkovic, S; Popovic, V

2011-01-01

29

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

PubMed Central

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

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

2005-01-01

30

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

PubMed Central

Single nucleotide polymorphisms (SNPs), R990G and A986S of the calcium sensing receptor (CaSR) gene, are shown to influence response of parathyroid hormone (PTH) in subjects with optimal vitamin D levels. This cross-sectional study was conducted in subjects with vitamin D deficiency (VDD) to observe associations between CaSR polymorphisms, plasma iPTH, and serum calcium levels. Adult females (n = 140) with known VDD, intact parathyroid hormone (iPTH), and calcium levels were recruited for genotype analysis. The frequencies of the 986 alleles GG, GT, and TT were 68%, 25%, and 7%, respectively, whereas the frequencies of the 990 alleles AA, AG, and GG were 80%, 8.9%, and 11.1%, respectively. The subjects with GG genotype of R990G polymorphism had higher iPTH levels (148.65 versus 91.47 and 86.1?pg/mL for GG versus AA, AG, resp., P = 0.008) and lower calcium levels (8.4 versus 9.04 and 9.07?mg/dL for GG versus AA, AG, resp., P = 0.002). No such association of A986S polymorphism with plasma iPTH or serum calcium levels was observed in the present study. Patients with VDD bearing the GG genotype of R990G SNPs are prone to have higher iPTH levels and lower calcium. PMID:25695075

Majid, Hafsa; Khan, Aysha Habib

2015-01-01

31

Changes in the Calcium-Parathyroid Hormone-Vitamin D Axis and Prognosis for Critically Ill Patients: A Prospective Observational Study  

PubMed Central

Objective Vitamin D deficiency is prevalent in critically ill patients and may contribute to suboptimal clinical outcomes, but little is known about alterations of the calcium-parathyroid hormone (PTH)-vitamin D axis and prognosis in these individuals. Methods A prospective observational study was conducted on 216 patients admitted to a university-affiliated, tertiary-care medical intensive care unit(MICU) between June 2011 and December 2012. Serum levels of 25-hydroxyvitamin D, ionised calcium and intact PTH were determined within 24 h of MICU admission. The primary end point was all-cause hospital mortality within 90-days of admission. Results 95 patients (44%) showed 25-hydroxyvitamin D deficiency. Patients deficient in vitamin D showed significantly higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score, rate of positive blood culture, incidence of multiple organ dysfunction syndrome, and 90-day mortality rate than did patients with vitamin D insufficiency or sufficiency (P<0.05), as well as lower levels of serum IgG. 25-Hydroxyvitamin D deficiency was identified as an independent risk factor for mortality (OR?=?3.018, 95%CI 1.329–6.854, P?=?0.008). Hypovitaminosis D in PTH-responders was associated with higher mortality than was the same condition in non-responders (P<0.05). Conclusions These results suggest that vitamin D deficiency is prevalent among MICU patients, suggesting a significant derangement of the calcium-PTH-vitamin D axis in critically ill patients. Vitamin D deficiency is an independent risk factor for 90-day mortality, and hypovitaminosis D in PTH-responders is associated with higher mortality than is the same condition in non-responders. PMID:24073266

Zhao, Xiaoqin; Chen, Qiang; Chen, Zhaoyan; Qin, Hua; Qin, Yingfen; Liang, Xinghuan; Suo, Yingjun

2013-01-01

32

Parathyroid Hormone Levels and Cognition  

NASA Technical Reports Server (NTRS)

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

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

2009-01-01

33

Therapeutic potential of parathyroid hormone  

Microsoft Academic Search

Teriparatide, recombinant human parathyroid hormone (1-34) (rhPTH [1-34]), is approved for the treatment of osteoporosis in\\u000a men and postmenopausal women at high risk for fracture. The best candidates are those who have already had vertebral compression\\u000a fractures (symptomatic or asymptomatic) or other osteoporosis-related fractures, or those who have very low bone mineral density,\\u000a in the T score range of -3.5

Felicia Cosman; Robert Lindsay

2004-01-01

34

21 CFR 862.1545 - Parathyroid hormone test system.  

Code of Federal Regulations, 2013 CFR

... 2013-04-01 false Parathyroid hormone test system. 862.1545 Section 862...Test Systems § 862.1545 Parathyroid hormone test system. (a) Identification. A parathyroid hormone test system is a device intended to...

2013-04-01

35

21 CFR 862.1545 - Parathyroid hormone test system.  

Code of Federal Regulations, 2012 CFR

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

2012-04-01

36

21 CFR 862.1545 - Parathyroid hormone test system.  

Code of Federal Regulations, 2014 CFR

... 2014-04-01 false Parathyroid hormone test system. 862.1545 Section 862...Test Systems § 862.1545 Parathyroid hormone test system. (a) Identification. A parathyroid hormone test system is a device intended to...

2014-04-01

37

21 CFR 862.1545 - Parathyroid hormone test system.  

Code of Federal Regulations, 2011 CFR

... 2011-04-01 false Parathyroid hormone test system. 862.1545 Section 862...Test Systems § 862.1545 Parathyroid hormone test system. (a) Identification. A parathyroid hormone test system is a device intended to...

2011-04-01

38

21 CFR 862.1545 - Parathyroid hormone test system.  

Code of Federal Regulations, 2010 CFR

... 2010-04-01 false Parathyroid hormone test system. 862.1545 Section 862...Test Systems § 862.1545 Parathyroid hormone test system. (a) Identification. A parathyroid hormone test system is a device intended to...

2010-04-01

39

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

PubMed

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

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

2014-11-22

40

[Parathyroid hormone and Wnt signaling].  

PubMed

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

Tamura, Yukinori; Kaji, Hiroshi

2013-06-01

41

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

PubMed Central

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

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

2012-01-01

42

DNA patterns in parathyroid disease predict postoperative parathyroid hormone secretion.  

PubMed

Flow cytometric analysis of the nuclear deoxyribonucleic acid (DNA) content of parathyroid glands excised from patients with hypercalcemic hyperparathyroidism has identified three distinct DNA patterns. The most frequent pattern showed a high percentage of cells with tetraploid DNA, which indicated an increase in the G2 and M phase of the cell cycle. Thirty-four patients were found to have abnormal tetraploid DNA content. One patient had a normal diploid pattern, and seven were found to have an aneuploid DNA population in their excised parathyroid glands. This unexpected finding of aneuploid DNA appears to be an unique feature of these endocrine glands because they have no histologic or clinical characteristics of malignant change. All patients have remained normocalcemic and clinically well after excision of only grossly enlarged glands. Postoperative parathyroid hormone (PTH) levels were correlated in 17 patients with DNA analyses of biopsy specimens from 30 normal-sized glands which were left in situ. Seven patients with elevated PTH postoperatively had high tetraploid or aneuploid DNA in all 13 glands from which biopsy specimens had high tetraploid or aneuploid DNA in all 13 glands from which biopsy specimens had been taken. In 10 patients with normal PTH levels, six had normal diploid patterns, whereas four had high tetraploid DNA in their gland biopsy specimens. DNA content present in biopsy specimens of normal-sized, in situ glands was predictive (p less than 0.042) of parathyroid gland secretory activity. These findings suggest that the stimulus for parathyroid gland hyperfunction often affects more than a single enlarged gland and persists after clinical cure, as shown by a more rapid cell turnover in some remaining glands and continued hypersecretion of hormone. PMID:3194838

Irvin, G L; Taupier, M A; Block, N L; Reiss, E

1988-12-01

43

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

PubMed Central

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

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

2014-01-01

44

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

Microsoft Academic Search

Proliferation of parathyroid cells negatively correlates with expression of parathyroid hormone-related protein in secondary parathyroid hyperplasia.BackgroundParathyroid hormone–related protein (PTHrP) is now suspected to act as an autocrine or paracrine regulator of cell growth or differentiation, although it was originally reported as a hypercalcemic substance in malignancies. This study was performed to assess the relationship between PTHrP expression and cell proliferation

HIROSHI MATSUSHITA; MITSURU HARA; YUZO ENDO; YOSHIMASA SHISHIBA; SHIGEKO HARA; YOSHIFUMI UBARA; HIDEKI NAKAZAWA; NORIYUKI SUZUKI; KATSUHIKO KAWAMINAMI; TERUHIKO KIDO; QING LI; LARS GRIMELIUS

1999-01-01

45

Anabolic effects of parathyroid hormone on bone  

Microsoft Academic Search

Parathyroid hormone (PTH) is classically considered to be a bone catabolic agent; however, when delivered intermittently at low doses, PTH potently stimulates cortical and\\/or trabecular bone growth in animal and clinical studies. Understanding the mechanism of PTH's osteopenic actions has led to the making of small, novel, and possibly noninjectable PTH analogues that can build biomechanically normal bone in osteopenic

Paul Morley; James F. Whitfield; Gordon E. Willick

1997-01-01

46

Parathyroid hormone--possible future drug for orthopedic surgery.  

PubMed

Parathyroid hormone naturally secreted by the parathyroid glands is a potent anabolic agent for bone. Parathyroid hormone is primarily thought of as a catabolic protein involved in the physiologic release of calcium from bone. Whereas during recent years, a number of animal studies and clinical trials have demonstrated that intermittent parathyroid hormone administration induces anabolic effects on both cancellous and cortical bone, enhances bone mass and increases mechanical strength of the bones. Most of the studies, both animal and human, have addressed the treatment of osteoporosis and parathyroid hormone represents an important new advance in the therapy of osteoporosis. Few studies have investigated the effect of intermittent parathyroid hormone treatment in the field of orthopedics on fracture healing and fixation of orthopedic implants. The results of those studies indicated an enhancement of fracture healing, faster bone repair and better fixation of the implant. Recently there were few animal studies started to investigate the effects of parathyroid hormone treatment on bone formation in regenerated and surrounding bone of distracted callus during limb lengthening. Distraction osteogenesis is a technique for bone lengthening that is widely used clinically and experimentally. Newly forming bone during distraction osteogenesis is expected to be an appropriate pattern for parathyroid hormone anabolic effect. Preclinical studies as well as clinical trials suggest that parathyroid hormone might be useful as a stimulator of bone formation whereas a lot of questions regarding parathyroid hormone therapy remain unanswered and require further experimental studies and investigations. PMID:15456969

Aleksyniene, Ramune; Hvid, Ivan

2004-01-01

47

Preoperative localization of suspicious parathyroid adenomas by assay of parathyroid hormone in needle aspirates  

Microsoft Academic Search

Objective: To determine the usefulness of parathyroid hormone (PTH) measurement in needle aspirates of a suspicious neck mass to confirm its parathyroid nature in patients with primary hyperpara- thyroidism. Methods: Thirty-three patients with surgically proved primary hyperparathyroidism were submitted to neck ultrasound (US), parathyroid scintigraphy, and assay of PTH in the aspirate (PTHa) of the suspicious cervical mass. Results: Based

C Marcocci; S Mazzeo; G Bruno-Bossio; A Picone; E Vignali; M Ciampi; P Viacava; A G Naccarato; P Miccoli; P Iacconi; A Pinchera

1998-01-01

48

An investigation into a possible relationship between vitamin D, parathyroid hormone, calcium and magnesium in a normally pigmented and an albino rural black population in the Northern Province of South Africa.  

PubMed

Vitamin D levels are important in the management of patients with various disorders of calcium metabolism associated with rickets, osteomalacia, osteodystrophy osteoporosis and hypoparathyroidism. 82 albinos and 58 normally pigmented children resident at the Siloe School for the Visually Impaired were sampled. Blood samples of fasting subjects were collected over a two-day period and analyzed for vitamin D, parathyroid hormone, plasma calcium and both plasma and red blood cell magnesium measurements. The height and weight of each subject was also recorded. The results are discussed in relation to the different skin pigmented groups, for specific age groups, sex and visual status. Statistical outliers were excluded from the results. It appears that the Albino group has significantly (p = 0.06) higher vitamin D levels against the background of a similar dietary intake and similar exposure to sunlight/day length. Thus black children/subjects require a significantly higher intake of vitamin D to attain the same level as their Albino counterparts. In spite of significantly higher vit D levels, the other homeostatic control mechanisms were not altered (i.e., PTH levels are similar in both groups). This study supports the postulate that a dark complexion predisposes to sub-optimal vit D status. PMID:10705955

Cornish, D A; Maluleke, V; Mhlanga, T

2000-01-01

49

Parathyroid hormone and parathyroid hormone-related protein analogs as therapies for osteoporosis.  

PubMed

Osteoporotic fractures result in significant morbidity and mortality. Anabolic agents reverse the negative skeletal balance that characterizes osteoporosis by stimulating osteoblast-dependent bone formation to a greater degree than osteoclast-dependent bone resorption. Parathyroid hormone (PTH) and parathyroid hormone- related protein (PTHrP) are peptide hormones, which have anabolic actions when administered intermittently. The only FDA-approved anabolic bone agent for the treatment of osteoporosis in the United States is PTH 1-34, or teriparatide, administered by daily subcutaneous injections. However, PTH 1-84 is also available in Europe. Synthetic human PTHrP 1-36 and a PTHrP 1-34 analog, BA058, have also been shown to increase lumbar spine bone density. These agents and several other PTH and PTHrP analogs, including some which are not administered as injections, continue to be investigated as potential anabolic therapies for osteoporosis. PMID:24078470

Augustine, Marilyn; Horwitz, Mara J

2013-12-01

50

Rapid Parathyroid Hormone Analysis During Venous Localization  

PubMed Central

Objective To determine the usefulness of the rapid parathyroid hormone (PTH) assay during venous localization for primary hyperparathyroidism (1° HPTH). Summary Background Data Remedial exploration for persistent 1° HPTH poses a significant challenge when noninvasive preoperative localization studies are negative. Based on experience with the intraoperative rapid PTH assay, this technique was extrapolated to the interventional radiology suite and generated near real-time data for the interventional radiologist employing on-site hormone analysis, with a 12-minute turnaround time from blood sampling to assay result. Methods Between November 1997 and July 2002, 446 patients with 1° HPTH were referred for treatment. Of these, 56 (12.5%) represented remedial patients who had each undergone one or more previous cervical explorations. Noninvasive imaging studies were positive for or suggestive of localized disease in 49/56 (87.5%) of these patients, who therefore proceeded directly to surgical exploration. Seven patients with persistent 1° HPTH and negative noninvasive studies underwent selective venous sampling employing a rapid PTH assay in the interventional suite. Results Venous localization demonstrated an apparent PTH gradient in six of the seven patients. In three, a subtle gradient demonstrated in near real-time prompted additional sampling, which confirmed an unequivocal hormone gradient. In an additional case, the absence of a gradient on initial sampling prompted further sampling, which was positive. All of the patients were explored, and in five of the six patients with a positive PTH gradient, a parathyroid adenoma (mean weight 636 ± 196 mg) was resected from a location predicted by venous localization. In the sixth patient with a positive gradient, parathyroid tissue was not identified; however, there was a significant fall in the intraoperative PTH values, and immediate postoperative and follow-up laboratory data at 1 month are indicative of a cure. In the one patient with negative localization, abnormal parathyroid tissue could not be located during surgical exploration. Conclusions The rapid PTH assay is a major adjunct for obtaining informative venous localization in patients with persistent 1° HPTH. This information is extremely helpful to the surgeon in this challenging group of patients and resulted in a 100% cure rate when a venous gradient was demonstrated. The authors now employ this technique routinely in remedial patients with negative noninvasive imaging studies. PMID:12724638

Udelsman, Robert; Aruny, John E.; Donovan, Patricia I.; Sokoll, Lori J.; Santos, Florie; Donabedian, Richard; Venbrux, Anthony C.

2003-01-01

51

25 hydroxy-vitamin D(3)-1alpha hydroxylase expression and activity in cultured human osteoblasts and their modulation by parathyroid hormone, estrogenic compounds and dihydrotestosterone.  

PubMed

Human osteoblasts (hOB) produce and respond to 1,25(OH)(2)D(3) (1,25D), suggesting an autocrine/paracrine system. We therefore examined hormonal modulation of the expression and activity of 25 hydroxy-vitamin D(3)-1alpha hydroxylase (1-Ohase) in hOB. Cells from pre- and post-menopausal women or men, were treated with estrogenic compounds and 1-OHase expression and activity were measured. 1-OHase mRNA expression was highest in pre-menopausal women hOB and was increased by all hormones tested. In post-menopausal hOB all hormones except biochainin A (BA) and genistein (G) increased 1-OHase mRNA expressions to less extent. In male-derived hOB only dihydrotestosterone (DHT) and carboxy BA (cBA) increased 1-OHase mRNA expression. 1,25D production from 25(OH)D(3) had a K(m) of approximately 769-400 ng/ml (1.92-1.07 microM) and V(max) of 31.3-17.4 ng/ml (0.078-0.044 microM/60 min/5 x 10(6)cells) respectively, and was increased by all hormones except raloxifene (Ral) with higher stimulation in pre- than in post-menopausal cells. Only BA was almost five times more potent in pre- rather than post-menopausal hOBs. In male hOB only DHT and cBA increased 1,25D production whereas estradiol-17beta (E(2)) had no effect and BA decreased it. These results provide evidence for the expression of 1-OHase mRNA and production of 1,25D in hOBs, which are age and sex dependent and are hormonally modulated. The role of this local autocrine/paracrine 1,25D system in bone physiology deserves further investigation. PMID:17659868

Somjen, Dalia; Katzburg, Sara; Stern, Naftali; Kohen, Fortune; Sharon, Orly; Limor, Rona; Jaccard, Niva; Hendel, David; Weisman, Yosef

2007-01-01

52

Parathyroid carcinoma: location of pelvic metastases by parathyroid hormone assay  

PubMed Central

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

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

1974-01-01

53

Parathyroid hormone response to hypocalcaemia following hypercalcaemia.  

PubMed

Experiments were designed to study the ability of calcium infusions to suppress parathyroid hormone (PTH) responses to hypocalcaemia, induced by iv infusions of ethylene-glycol-bis(beta-aminoethylether)N,N'-tetraacetate (EGTA). When plasma calcium (Ca) was raised for 60 min to levels higher then 2.6 mmol/l, PTH responses to a subsequent fall of Ca due to EGTA infusions for 7 min were significantly reduced (P < 0.02) or abolished when compared to PTH responses during 7-min EGTA infusions in normocalcaemic animals. CaCl2 infusions lasting for 10 min only, however, did not cause a significant reduction of PTH responses to subsequent 7-min EGTA infusions. The results demonstrate, that raised Ca reduced PTH available for immediate release. This effect was time-dependent, since it was only seen, when CaCl2 was infused for more than 10 min prior to the administration of EGTA. PMID:6779477

Blum, J W; Kunz, P; Rodriguez, S M; Fischer, J A

1981-01-01

54

Effects of Parathyroid Hormone on Immune Function  

PubMed Central

Parathyroid hormone (PTH) function as immunologic mediator has become interesting with the recent usage of PTH analogue (teriparatide) in the management of osteoporosis. Since the early 1980s, PTH receptors were found on most immunologic cells (neutrophils, B and T cells). The in vitro evaluations for a possible role of PTH as immunomodulator have shown inconsistent results mainly due to methodological heterogeneity of these studies: it used different PTH formulations (rat, bovine, and human), at different dosages and different incubating periods. In some of these studies, the lymphocytes were collected from uremic patients or animals, which renders the interpretation of the results problematic due to the effect of uremic toxins. Parathyroidectomy has been found to reverse the immunologic defect in patients with high PTH levels. Nonetheless, the clinical significance of these findings is unclear. Further studies are needed to define if PTH does have immunomodulatory effects. PMID:20886005

Geara, Abdallah Sassine; Castellanos, Mario R.; Bassil, Claude; Schuller-Levis, Georgia; Park, Eunkue; Smith, Marianne; Goldman, Michael; Elsayegh, Suzanne

2010-01-01

55

[Rare abnormalities of parathyroid gland function and parathyroid hormone receptor action].  

PubMed

The parathyroid glands, located near or within the posterior surface of the thyroid gland and secreting parathyroid hormone, are essential organs for the regulation of calcium and phosphate metabolism. As they are necessary to sustain life and maintain homeostasis, undetected or misdiagnosed parathyroid disorders may pose a significant threat to health outcomes, as their presence may increase morbidity and mortality in affected individuals. The clinical picture of some disorders associated with abnormal parathyroid hormone secretion and receptor action is sometimes complicated by coexisting abnormalities, and in these cases establishing the correct diagnosis is challenging. The remarkable progress of recent years in the area of hormonal assessment, imaging procedures and molecular biology, has resulted in a great improvement in the identification, differentiation and treatment of various parathyroid disorders and has made it possible to identify several new clinical entities. In this paper, we discuss the present state-of-art on the etiopathogenesis, clinical manifestations, diagnosis and treatment of chosen rare abnormalities of parathyroid gland function and parathyroid hormone receptor action. PMID:24712267

Krysiak, Robert; Bartecka, Anna; Okopie?, Bogus?aw

2014-01-01

56

Safety of parathyroid hormone for the treatment of osteoporosis  

Microsoft Academic Search

Teriparatide (recombinant human 1-34 parathyroid hormone) has been registered for the treatment of postmenopausal osteoporosis\\u000a and osteoporosis in men for more than 5 years, whereas 1-84 parathyroid hormone has just recently been registered in Europe\\u000a for osteoporosis management. Therefore, more data are available regarding the long-term safety of teriparatide. The issues\\u000a to be considered are the effects of the registered

Paul D. Miller

2008-01-01

57

Degradation of parathyroid hormone in macrophage endosomes  

SciTech Connect

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.

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

1986-05-01

58

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

SciTech Connect

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

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

2011-04-15

59

Normal parathyroid hormone levels in a diabetic patient with parathyroid adenoma  

Microsoft Academic Search

Objective The incidence of diabetes mellitus in patients with primary hyperparathyroidism and, conversely, primary hyperparathyroidism\\u000a in diabetic patients are approximately threefold higher than the respective expected prevalence in the general populace. The\\u000a diagnosis is straightforward when the patient presents hypercalcemia and inappropriately elevated serum parathyroid hormone\\u000a (PTH) levels. We report a case of parathyroid adenoma in a diabetic patient with

Nese Ersoz Gulcelik; Fani Bozkurt; Gaye Güler Tezel; Volkan Kaynaroglu; Tomris Erbas

2009-01-01

60

Immunocytochemical staining patterns for parathyroid hormone and chromogranin in parathyroid hyperplasia, adenoma, and carcinoma  

Microsoft Academic Search

Parathyroid glands (PGs) contain less secretory granules with presumably less stored parathyroid hormone (PTH) than many other\\u000a endocrine glands. Immunocytochemical staining for PTH has been hindered by the lack of commercially available, reliable antibodies\\u000a against human PTH. By treating deparaffinized tissue sections with an antigen-retrieval procedure, immunocytochemical staining\\u000a for PTH and chromogranin A (CHA) was performed using commercially available monoclonal

Tatsuo Tomita

1999-01-01

61

Parathyroid hormone secretion during exchange transfusion.  

PubMed Central

Plasma concentrations of calcium, phosphate, citrate, albumin, and parathyroid hormone (PTH) were measured during and after exchange transfusion of infants suffering from haemolytic disease using blood anticoagulated with acid-citrate and dextrose (ACD) or heparin. Pretransfusion plasma PTH and phosphate both correlated positively with postnatal age but not with each other. Transfusion with ACD blood caused a twelvefold rise in plasma citrate levels but no significant change in plasma calcium, phosphate, or PTH of the infant, despite the concentration of these substances being lower in the donor blood. The concentration of calcium, phosphate, and albumin was higher in heparinized than in ACD donor blood, and infants transfused with heparinized blood showed no change in the plasma concentration of any substance measured during transfusion. The addition of 50 mug glucagon to ACD donor blood had no effect on PTH secretion. 3 hours after transfusion there was a rise in the plasma PTH infants who had received ACD blood but not in those given heparinized blood. Transfusion with ACD blood caused a net loss of calcium, phosphate and albumin from the infant, whereas transfusion with heparin blood did not. Both types of transfusion caused a net loss of PTH but this was significantly greater in those given ACD blood. These results show that transfusion with ACD blood results in increased secretion of PTH, probably due to the fall in ionized calcium concentration caused by the citrate load. PMID:1170813

Milner, R D; Woodhead, J S

1975-01-01

62

Parathyroid Hormone Applications in the Craniofacial Skeleton  

PubMed Central

Parathyroid hormone (PTH) is known for its ability to ‘build’ bone, with research in this area centered on its use as an osteoporosis therapeutic. Recent interest has developed regarding its potential for regenerative applications such as fracture healing and osseous defects of the oral cavity. Many years of investigation using murine gene-targeted models substantiate a role for signaling at the PTH/PTH-related protein (PTHrP) receptor (PPR) in intramembranous bone formation in the craniofacial region as well as in tooth development. Pre-clinical studies clearly support a positive role of intermittent PTH administration in craniofacial bones and in fracture healing and implant integration. A few human clinical studies have shown favorable responses with teriparatide (the biologically active fragment of PTH) administration. Favorable outcomes have emerged with teriparatide administration in patients with osteonecrosis of the jaw (ONJ). New delivery strategies are in development to optimize targeted application of PTH and to help maximize local approaches. The promising host-modulating potential of PTH requires more information to further its effectiveness for craniofacial regeneration and osseous wound-healing, including a better delineation of cellular targets, temporal effects of PTH action, and improved approaches for local/targeted delivery of PTH. PMID:23071071

Chan, H.L.; McCauley, L.K.

2013-01-01

63

Parathyroid hormone applications in the craniofacial skeleton.  

PubMed

Parathyroid hormone (PTH) is known for its ability to 'build' bone, with research in this area centered on its use as an osteoporosis therapeutic. Recent interest has developed regarding its potential for regenerative applications such as fracture healing and osseous defects of the oral cavity. Many years of investigation using murine gene-targeted models substantiate a role for signaling at the PTH/PTH-related protein (PTHrP) receptor (PPR) in intramembranous bone formation in the craniofacial region as well as in tooth development. Pre-clinical studies clearly support a positive role of intermittent PTH administration in craniofacial bones and in fracture healing and implant integration. A few human clinical studies have shown favorable responses with teriparatide (the biologically active fragment of PTH) administration. Favorable outcomes have emerged with teriparatide administration in patients with osteonecrosis of the jaw (ONJ). New delivery strategies are in development to optimize targeted application of PTH and to help maximize local approaches. The promising host-modulating potential of PTH requires more information to further its effectiveness for craniofacial regeneration and osseous wound-healing, including a better delineation of cellular targets, temporal effects of PTH action, and improved approaches for local/targeted delivery of PTH. PMID:23071071

Chan, H L; McCauley, L K

2013-01-01

64

Circulating parathyroid hormone and calcitonin in rats after spaceflight  

NASA Technical Reports Server (NTRS)

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

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

1992-01-01

65

Vitamin D: a pleiotropic hormone  

Microsoft Academic Search

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

Annemieke Verstuyf; Geert Carmeliet; Roger Bouillon; Chantal Mathieu

2010-01-01

66

Effect of parathyroid hormone on phosphate reabsorption in the presence of acetazolamide  

Microsoft Academic Search

Effect of parathyroid hormone on phosphate reabsorption in the presence of acetazolamide. The hypothesis that parathyroid hormone and carbonic anhydrase inhibitors have a common mechanism or site of action on phosphate reabsorption by the renal tubule was tested by administration of parathyroid hormone in the absence and presence of acetazolamide in thyroparathyroidectomized dogs. Re-collection micropuncture and electron probe microanalysis methodologies

Franklyn G Knox; John A Haas; Claude P Lechene

1976-01-01

67

Plasma concentrations of parathyroid hormone-related protein in dogs with potential disorders of calcium metabolism  

Microsoft Academic Search

The plasma concentrations of total calcium, ionised calcium, albumin, parathyroid hormone and parathyroid hormone-related protein (pthrp) were measured in 25 dogs with lymphoma, nine dogs with primary hyperparathyroidism and seven dogs with adenocarcinoma of the apocrine gland of the anal sac. Plasma total calcium, ionised calcium, albumin and parathyroid hormone-related protein were measured in 18 clinically normal control dogs. The

R. J. Mellanby; R. Craig; H. Evans; M. E. Herrtage

2006-01-01

68

Intraoperative parathyroid hormone assay-cutting the Gordian knot  

PubMed Central

Background: Hyperparathyroidism is treated by surgical excision of the hyperfunctioning parathyroid gland. In case of adenoma the single abnormal gland is removed, while in hyperplasias, a subtotal excision, that is, three-and-a-half of the four glands are removed. This therapeutic decision is made intraoperatively through frozen section evaluation and is sometimes problematic, due to a histological overlap between hyperplasia and the adenoma. The intraoperative parathyroid hormone (IOPTH) assay, propogated in recent years, offers an elegant solution, with a high success rate, due to its ability to identify the removal of all hyperfunctioning parathyroid tissue. Aim: To study the feasibility of using IOPTH in our setting. Materials and Methods: Seven patients undergoing surgery for primary hyperparathyroidism had their IOPTH levels evaluated, along with the routine frozen and paraffin sections. Results: All seven patients showed more than a 50% intraoperative fall in serum PTH after excision of the abnormal gland. This was indicative of an adenoma and was confirmed by histopathological examination and normalization of serum calcium postoperatively. Conclusion: The intraoperative parathyroid hormone is a sensitive and specific guide to a complete removal of the abnormal parathyroid tissue. It can be incorporated without difficulty as an intraoperative guide and is superior to frozen section diagnosis in parathyroid surgery. PMID:24741518

Tampi, Chandralekha; Chavan, Nitin; Parikh, Deepak

2014-01-01

69

Effect of phorbol myristate acetate on secretion of parathyroid hormone  

SciTech Connect

The influence of phorbol myristate acetate (PMA), an activator of protein kinase c, on the secretion of parathyroid hormone from collagenase-dispersed bovine parathyroid cells was tested. The cells were incubated at low or high concentrations of calcium in the medium, and the hormone secreted into the medium was measured by a radioimmunoassay that recognizes both intact and C-terminal fragments of hormone. A stimulatory effect of PMA at high calcium, seen at PMA concentrations as low as 1.6 nM, did not occur with a biologically inactive 4{alpha}-isomer of phorbol ester, and was independent of changes in cellular adenosine 3{prime},5{prime}-cyclic monophosphate levels. Examination of {sup 32}P-labeled phosphoproteins by two-dimensional gel electrophoresis revealed acidic proteins of {approximately}20,000 and 100,000 Da that were phosphorylated at low and high calcium + 1.6 {mu}M PMA but not at high calcium alone. The protein kinase c activity associated with the membrane fraction of parathyroid cells significantly decreased 40% when the cells were incubated at high vs. low calcium. The data suggest that calcium may regulate parathyroid hormone secretion through changes in protein kinase c activity of the membrane fraction of the cell and protein phosphorylation.

Morrissey, J.J. (Washington Univ. School of Medicine, St. Louis, MO (USA))

1988-01-01

70

Clinical uses for calciotropic hormones 1,25-dihydroxyvitamin D3 and parathyroid hormone-related peptide in dermatology: a new perspective.  

PubMed

The skin is not only the organ for the photosynthesis of vitamin D3, but also a target tissue for its activated form 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Vitamin D3 is absolutely essential for the development and maintenance of a healthy skeleton. Without an adequate source of vitamin D, children develop rickets and the elderly develop osteomalacia and exacerbation of osteoporosis. 1,25(OH)2D3 is a potent inhibitor of proliferation of epidermal cells and, with its analogs, it has been developed for the successful treatment of psoriasis. Not all psoriasis patients, however, respond to 1,25(OH)2D3 and its analogs. Evidence suggests that there may be a defect in the regulation of levels of mRNA for the vitamin D receptor in patients who have partial or no response to 1,25(OH)2D3 therapy. The degree of responsiveness to 1,25(OH)2D3 therapy may also be related to the allelic variations in the vitamin D receptor gene. Parathyroid hormone-related peptide is synthesized by the epidermis and is an endogenous antiproliferative factor. Parathyroid hormone-related peptide agonists and 1,25(OH)2D3 inhibit in vitro and in vivo epidermal proliferation, whereas parathyroid hormone-related peptide antagonists stimulate both epidermal proliferation and hair growth in vivo. Therefore, the calciotropic hormones 1,25(OH)2D3 and parathyroid hormone-related peptide have wide-ranging clinical applications in dermatology. PMID:9627684

Holick, M F; Chen, M L; Kong, X F; Sanan, D K

1996-04-01

71

Fibroblast growth factor-23 regulates parathyroid hormone and 1 -hydroxylase expression in cultured bovine parathyroid cells  

Microsoft Academic Search

Fibroblast growth factor-23 (FGF23) is a circulating factor that decreases serum levels of inorganic phosphate (Pi) as well as 1,25-dihydroxyvitamin D3. Recent studies also suggest a correlation between serum levels of FGF23 and parathyroid hormone (PTH) in patients with chronic kidney disease. It is, however, unknown whether FGF23 directly modulates PTH expression, or whether the correlation is secondary to abnormalities

Tijana Krajisnik; Peyman Bjorklund; Richard Marsell; Osten Ljunggren; G. Akerstrom; K. B Jonsson; G. Westin; T. E Larsson

2007-01-01

72

Sestamibi Scan–directed Parathyroid Surgery: Potentially High Failure Rate without Measurement of Intraoperative Parathyroid Hormone  

Microsoft Academic Search

The present study evaluated sestamibi scan–directed parathyroidectomy with intraoperative parathyroid hormone (PTH) assessment (ioPTH). The preoperative sestamibi scintigraphies were compared with the intraoperative findings for 103 patients undergoing first exploration for sporadic primary hyperparathyroidism (pHPT). Data were collected prospectively. Ninety-nine patients (96%) were cured. Patients with persistent pHPT ( n = 4) all had an incorrect scintigram as well as

Johan Westerdahl; Anders Bergenfelz

2004-01-01

73

Inhibition of Parathyroid Hormone Secretion by Caffeine in Human Parathyroid Cells  

PubMed Central

Context and Objective: Caffeine is a highly consumed psychoactive substance present in our daily drinks. Independent studies have reported associations between caffeine consumption, low bone mineral density, and urinary calcium loss, as well as impaired bone development in vitro and in vivo. Calcium (Ca2+), vitamin D, and PTH are critical regulators of bone remodeling. A possible association between caffeine and parathyroid gland function has been suggested in the literature. Design, Setting, and Patients: Effects of caffeine on PTH secretion and Ca2+ levels were determined by batch incubation and Fura-2, respectively, in pathological parathyroid cells. Protein expressions were studied by Western blot and immunohistochemistry in normal and parathyroid adenoma tissues. Alterations in gene expressions of adenosine receptor A1 (ADORA1) and A2 (ADORA2A) and PTH were quantified by PCR; intracellular cAMP levels and protein kinase A activity were analyzed by an antibody-based assay. Results: We studied physiological concentrations of caffeine ranging from 1 to 50 ?m and found that 50 ?m caffeine caused a significant decrease of PTH secretion and PTH gene expression. This decrease occurred in parallel with a decrease of the intracellular cAMP level, protein kinase A activity, and ADORA1 gene expression, indicating a possible causal relationship. The intracellular level of Ca2+ was unaffected even by high concentrations of caffeine. Protein expressions demonstrated two main targets for caffeine—ADORA1 and ADORA2A. Conclusion: A physiological high dose of caffeine inhibits PTH secretion in human parathyroid cells, possibly due to a decrease of the intracellular level of cAMP. The observation demonstrates a functional link between caffeine and parathyroid cell function. PMID:23788688

Farnebo, Lars-Ove; Bränström, Robert; Larsson, Catharina

2013-01-01

74

Parathyroid hormone and growth in chronic kidney disease  

Microsoft Academic Search

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.

Simon Waller

2011-01-01

75

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

PubMed Central

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

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

2013-01-01

76

The anabolic effects of parathyroid hormone therapy.  

PubMed

PTH represents an important new advance in the therapy of osteoporosis. As an anabolic agent, its potential might be substantially greater than that of antiresorptive agents. Clear evidence in human trials now documents the ability of PTH to stimulate cancellous bone formation and to reduce fractures. Because antiresorptive agents and PTH work by distinct mechanisms of action, it is possible that the combination of these agents could be significantly more potent than either agent alone. There are other unanswered questions about PTH. More studies are needed to document an anabolic effect on cortical bone. In addition, more large-scale studies are needed to further determine the reduction in nonvertebral fractures with PTH, especially at the hip. More information is also required to determine the possible need for antiresorptive therapy after PTH. Protocols to consider PTH as an intermittent recycling therapy would be of interest. In the future, PTH is likely to be modified for easier and more targeted delivery. Oral or transdermal delivery systems may become available. Recently, Gowen et al [78] have described an oral calcilytic molecule that antagonizes the parathyroid cell calcium receptor, thus stimulating the endogenous release of PTH. This approach could represent a novel endogenous delivery system for intermittent PTH administration. Ultimately, when the anabolic and catabolic mechanisms of PTH can be clearly distinguished, both mechanistically and in molecular terms, it may be possible to develop PTH analogs that are more purely anabolic. PMID:12916294

Rubin, Mishaela R; Bilezikian, John P

2003-05-01

77

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

SciTech Connect

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

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

2009-08-18

78

[Parathyroid and bone. The mechanism of anabolic function of parathyroid hormone on bone].  

PubMed

Parathyroid hormone (PTH) has been applied to postmenopausal women and several studies revealed that intermittent PTH treatment significantly increases lumbar bone mineral density and reduces fracture risk. However, the mechanism of PTH anabolic function on bone is not fully understood yet. PTH receptors (PPR) are expressed in osteoblasts and PPR stimulates multiple intracellular signal pathways, including those mediated by cAMP-PKA signaling pathway and PLC-PKC signaling pathway. Several studies demonstrate that the PKA signaling through G-proteins in osteoblasts play important roles in regulating gene expression and osteogenesis by PTH. PMID:18057659

Ogata, Naoshi; Kawaguchi, Hiroshi

2007-12-01

79

[Parathyroid and bone. Role of parathyroid hormone in the treatment of osteoporosis].  

PubMed

Parathyroid hormone (PTH) , a potent anabolic agent, produces larger increments in bone mass than those seen with antiresorptive agents. No further benefit is expected in PTH and antiresorptive combinations in treatment-naïve patients of osteoporosis, but in cases achieving the plateau level of BMD with established alendronate PTH can stimulate bone formation and increase BMD again. Alendronate treatment after PTH therapy can maintain gains in BMD at lumbar spine and hip as well. Many possibilities are expected in the role of PTH therapy in osteoporosis treatment. PMID:18057656

Nakamura, Toshitaka

2007-12-01

80

Serum 25-hydroxyvitamin D and parathyroid hormone levels in relation to blood pressure in a cross-sectional study in older Chinese men  

Microsoft Academic Search

Vitamin D status, parathyroid hormone (PTH) level and their associations with blood pressure in Chinese population are unknown. This study examined these associations in older Chinese men. Blood pressure, serum 25-hydroxyvitamin D (25OHD) and PTH was measured in 939 community-dwelling Chinese men aged 65 years and older. Linear regression analyses were performed with adjustments for age, body mass index, education,

R Chan; D Chan; J Woo; C Ohlsson; D Mellström; T Kwok; P Leung

2012-01-01

81

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, ...

82

Three-Phase Model Harmonizes Estimates of the Maximal Suppression of Parathyroid Hormone by 25-Hydroxyvitamin D in Persons 65 Years of Age and Older 1–3  

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 2-phase regression approach used, 2 d...

83

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

Microsoft Academic Search

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

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

84

Effect of parathyroid hormone on elastase release from human polymorphonuclear leucocytes  

Microsoft Academic Search

Effect of parathyroid hormone on elastase release from human polymorphonuclear leucocytes. Acute and chronic renal failure are clinical states associated with secondary hyperparathyroidism and increased catabolism. It has been suggested that elevated proteolytic activity is present in the blood in these clinical states. It is, theoretically, possible that the excess blood levels of parathyroid hormone (PTH) in patients with these

Shaul G Massry; Roland M Schaefer; Markus Teschner; Margarete Roeder; James F Zull

1989-01-01

85

Effects of Parathyroid Hormone on Skeletal Muscle Protein and Amino Acid Metabolism in the Rat  

PubMed Central

Because prominent skeletal muscle dysfunction and muscle wasting are seen in both chronic uremia and in primary hyperparathyroidism, and because markedly elevated parathyroid hormone levels occur in both disorders, potential effects of parathyroid hormone on skeletal muscle protein, amino acid, and cyclic nucleotide metabolism were studied in vitro using isolated intact rat epitrochlearis skeletal muscle preparations. Intact bovine parathyroid hormone and the synthetic 1-34 fragment of this hormone stimulated the release of alanine and glutamine from muscle of control but not from chronically uremic animals. This stimulation was dependent upon the concentration of parathyroid hormone added: At 105 ng/ml parathyroid hormone increased alanine release 84% and glutamine release 75%. Intracellular levels of alanine and glutamine were not altered by parathyroid hormone. Increasing concentrations of the 1-34 polypeptide decreased [3H]leucine incorporation into protein of muscles from both control and uremic animals. Using muscles from animals given a pulse-chase label of [guanido-14C]arginine in vivo, parathyroid hormone increased the rate of loss of 14C label from acid-precipitable protein during incubation and correspondingly increased the rate of appearance of this label in the incubation media. Parathyroid hormone increased muscle cAMP levels by 140% and cGMP levels by 185%, but had no effect on skeletal muscle cyclic nucleotide phosphodiesterase activities as assayed in vitro. Adenylyl cyclase activity in membrane preparations from control but not uremic rats was stimulated by parathyroid hormone in a concentration-dependent fashion. However, no stimulation of guanylyl cyclase activity was noted by parathyroid hormone, although stimulation by sodium azide was present. Incubation of muscles with added parathyroid hormone produced a diminished responsiveness towards epinephrine or serotonin regulation of amino acid release and cAMP formation in the presence compared to the absence of parathyroid hormone. In the absence of parathyroid hormone, detectable inhibition of alanine and glutamine release was produced by 10?9 M epinephrine, whereas in the presence of parathyroid hormone (1,000 ng/ml) inhibition of alanine and glutamine release required 10?6 M or greater epinephrine. Resistance to cyclic AMP action as well as inhibition of cyclic AMP formation by parathyroid hormone was found. Preincubation of rat sarcolemma with 1-34 parathyroid hormone produced a decreased activity of the isoproterenol-stimulable adenylyl cyclase activity but there was no apparent change in the concentration of isoproterenol required for one-half maximal and maximal stimulation of the enzyme. These findings suggest that high levels of parathyroid hormone have direct effects on skeletal muscle protein, amino acid, and cyclic nucleotide metabolism in muscle of normal but not uremic animals. Treatment with these high levels of parathyroid hormone in vitro appears to reproduce in normal muscle, the metabolic deficits and loss of hormone responsiveness observed in muscle of chronically uremic animals. It is therefore possible that direct effects of parathyroid hormone on skeletal muscle may account in part for the muscle dysfunction and wasting of primary hyperparathyroidism and chronic uremia. PMID:6306055

Garber, Alan J.

1983-01-01

86

Association of Leptin, 25-Hydroxyvitamin D, and Parathyroid Hormone in Women  

PubMed Central

Vitamin D deficiency and adipocytokines have been implicated in the etiology of aging-related diseases such as cancer, osteoporosis, and diseases of the cardiovascular system. The association between elevated parathyroid hormone (PTH) and low 25-hydroxyvitamin D(25-OH-VitD) in plasma is used to define vitamin D deficiency, yet their associated mechanistic pathways are unclear. Utilizing plasma samples from women in a previous intervention study, we measured plasma 25-OH-VitD, leptin, adiponectin, PTH, and lipid levels. We observed strong positive associations for leptin with PTH, ?-tocopherol, and body mass index (BMI) and inverse associations with 25-OH-VitD and adiponectin. Although commonly accepted that vitamin D deficiency causes hyperparathyroidism, we observed this association primarily in individuals with elevated leptin levels, suggesting that leptin may be an important modifier of this effect consistent with 25-OH-VitD-mediated inhibition of leptin. Leptin was highly correlated with the BMI/25-OH-VitD ratio (r = 0.80; P < 0.0001), consistent with a model in which BMI (adiposity) and 25-OH-VitD are the primary determinants of circulating leptin and PTH levels. This model may explain the failure of some studies to observe elevated PTH in vitamin D deficient adolescents and provides important insight into epidemiological studies exploring the associations of these individual biomarkers with chronic disease risk and mortality. PMID:19235038

Maetani, Micah; Maskarinec, Gertraud; Franke, Adrian A.; Cooney, Robert V.

2015-01-01

87

Decrease in vitamin D receptor and calcium-sensing receptor in highly proliferative parathyroid adenomas  

Microsoft Academic Search

Objective: A significant decrease in vitamin D receptor (VDR) and calcium-sensing receptor (CaSR) protein expression has been demonstrated recently in parathyroid (PT) adenomas. In this study, we investigated the relationships between the proliferative activity of parathyroid glands (PTGs) and the expression of VDR as well as CaSR, and compared it with the clinical severity in patients with primary hyperparathyroidism (18HPT).

Shozo Yano; Toshitsugu Sugimoto; Tatsuo Tsukamoto; Kazuo Chihara; Akira Kobayashi; Sohei Kitazawa; Sakan Maeda; Riko Kitazawa

2003-01-01

88

Osteoblast hydraulic conductivity is regulated by calcitonin and parathyroid hormone  

NASA Technical Reports Server (NTRS)

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

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

1996-01-01

89

Influence of parathyroid hormone on bone cell ultrastructure  

SciTech Connect

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

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

1981-05-01

90

In vitro perifusion for the study of parathyroid hormone secretion: Effects of extracellular calcium concentration and beta-adrenergic regulation on bovine parathyroid hormone secretion in vitro  

Microsoft Academic Search

Summary  An in vitro perifusion system was used to study parathyroid hormone (PTH) secretion in response to calcium (Ca) and beta-adrenergic\\u000a agents. Perifused parathyroid tissue responded to changes in Ca within the physiologic range during experiments up to 5 h.\\u000a There was rapid secretory stimulation after exposure to low Ca, with the maximum response being observed at 20 min. Normal\\u000a bovine

David A. Hanley; Kensuke Takatsuki; Maria E. Birnbaumer; Arthur B. Schneider; Louis M. Sherwood

1980-01-01

91

Parathyroid carcinoma survival: improvements in the era of intact parathyroid hormone monitoring?  

PubMed Central

The intact parathyroid hormone (iPTH) assay is a critical test in the diagnosis and management of PTH-mediated hypercalcemia, including parathyroid carcinoma (PCa). We hypothesized that the survival of patients diagnosed with PCa has improved since adoption of the iPTH assay into clinical practice. We identified all confirmed cases of PCa within the Surveillance, Epidemiology and End Results database from 1973 to 2006. Patients were categorized into two eras based upon introduction of the iPTH assay: 1973 to 1997 (era I) and 1997 to 2006 (era II, when the iPTH assay was in standard use). We estimated overall survival (OS) and disease-specific survival (DSS) using the Kaplan-Meier method, with differences among survival curves assessed via log rank. Multivariate Cox proportional hazards models compared the survival rates between treatment eras while controlling for patient age, sex, race/ethnicity, tumor size, nodal status, extent of disease, and type of surgery. Multivariate models included patients undergoing potentially curative surgery and excluded those with distant metastases. Risks of overall and disease-specific mortality were reported as hazard ratios with 95% confidence intervals. Study criteria were met by 370 patients. Median survival was 15.6 years. Five-year rates of OS and DSS were 78% and 88% for era I and 82% and 96% for era II. On multivariate analysis, age, black race, and unknown extent of disease predicted an increased risk of death from any cause. Treatment era did not predict OS. No factor predicted PCa-specific mortality. In multivariate analysis, neither OS nor DSS have improved in the current era that utilizes iPTH for the detection and management of PCa. PMID:23772298

Allen, Miya E.; Semrad, Alison; Yang, Anthony D.; Martinez, Steve R.

2013-01-01

92

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

E-print Network

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

Eisenberg, Rahel E. (Rahel Esther)

2009-01-01

93

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

E-print Network

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...

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

2012-06-12

94

Desensitization of parathyroid hormone receptors on cultured bone cells  

SciTech Connect

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.

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

1990-12-01

95

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

Microsoft Academic Search

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

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

1999-01-01

96

Parathyroid hormone is not an inhibitor of lipoprotein lipase activity.  

PubMed

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

Arnadottir, M; Nilsson-Ehle, P

1994-01-01

97

Catabolic and anabolic actions of parathyroid hormone on the skeleton  

PubMed Central

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

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

2015-01-01

98

Parathyroid hormone-related protein in teleost fish.  

PubMed

A brief description is given of the discovery of PTHrP and the roles of the peptide in mammalian physiology. Next, the occurrence of PTHrP in the earliest vertebrates, sharks, skates and fishes, is reviewed and the calciotropic functions of PTHrP are addressed more specifically in fishes. Parathyroid hormone-related protein (PTHrP) is a hypercalcemic hormone in teleostean fishes, but also has para- and autocrine functions. After the isolation and identification of fish PTHrP and PTHrP receptors and the subsequent development of recombinant protein and a real-time quantitative PCR, a calciotropic role of PTHrP in fish physiology could be assessed. PTHrP influences calcium physiology via regulation of calcium mobilisation from internal sources (bone and scales) and via calcium uptake from the environment (water and diet). Continuous variations in the need for calcium and in the availability of environmental calcium require fast calciotropes to guarantee calcium balance, in which PTHrP is pivotal for the fish. PTHrP is essential in fish bone physiology, e.g. in mineralisation and calcium reabsorption from the scales. Moreover, PTHrP plays a role in vitellogenesis, cortisol production, regulation of renal Mrp2 activity and melatonin synthesis. The plethora of functions of PTHrP in fish concern endocrine, paracrine and autocrine (and possibly intracrine) functions; calciotropic actions of PTHrP at the organismal and cellular level are prominent in fish. The strong conservation of the pthrp gene in the vertebrate lineage and the N-terminal similarity of the coded proteins relates to the important role of PTHrP in calcium physiology that is of paramount importance to all physiological processes. Recent and ongoing studies will contribute to our rapidly expanding knowledge of the original physiological functions of PTHrP in teleost fish. PMID:17188690

Abbink, Wout; Flik, Gert

2007-01-01

99

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

Microsoft Academic Search

:   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

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

2001-01-01

100

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...

101

Sestamibi Scanning and Minimally Invasive Radioguided Parathyroidectomy Without Intraoperative Parathyroid Hormone Measurement  

PubMed Central

Objective To evaluate the results of a large series of patients undergoing minimally invasive radioguided parathyroidectomy (MIRP) in which routine use of the intraoperative parathyroid hormone assay was not used, and to investigate characteristics between patients who had positive preoperative parathyroid scans versus those with negative scans. Summary Background Data The technique of parathyroidectomy has traditionally involved bilateral exploration of the neck under general endotracheal anesthesia. Parathyroid imaging using technetium-99m sestamibi (MIBI) has evolved and can localize the adenomas in 80% to 90% of patients. The MIRP technique combines parathyroid scintigraphy with a hand-held gamma detector used intraoperatively to guide the surgeon to the adenoma in patients with positive MIBI scans. Central to this technique or other unilateral approaches is a positive MIBI scan. Methods One hundred seventy-three atients with primary hyperparathyroidism operated on by a single surgeon between January 1998 and July 2002 were included. One hundred twelve patients underwent the MIRP procedure and by definition had a positive preoperative parathyroid scan. The technique involved injecting 20 mCi MIBI 1 hour before the surgical procedure in patients who preoperatively had positive MIBI imaging. Patients had the choice of general or MAC anesthesia. Using an incision of less than 4 cm, the dissection to the adenoma was guided by the Navigator 11-mm probe. These 112 patients and 4 additional patients who for various reasons did not have the MIRP procedure yet had positive MIBI scans were compared to 57 patients who had clearly negative MIBI parathyroid imaging. Results Follow-up data were available for 108 of 112 patients who underwent MIRP. No patients had persistent hypercalcemia. The long-term success rate for the MIRP group was 98%. Fifty-two percent of the MIRP procedures were performed using MAC anesthesia. Overall, gland weight and serum PTH were related to the probability of a positive MIBI scan. Multiple logistic regression revealed that females were more likely to exhibit positive scans than were males for any fixed serum PTH level. For females, there was a significant relationship between increasing serum parathyroid hormone and a positive MIBI scan. Conversely, in males, the relationship between scan positivity and serum parathyroid hormone was weaker. Conclusions The MIRP technique without routine intraoperative serum parathyroid hormone measurement resulted in an excellent cure rate for primary hyperparathyroidism. As the MIRP technique as well as other techniques for unilateral cervical exploration are predicated on a positive parathyroid scan, the possible effect of gender on the sensitivity of MIBI scintigraphy for the detection of parathyroid adenomas warrants further investigation. PMID:12724639

Goldstein, Richard E.; Billheimer, Dean; Martin, William H.; Richards, Ken

2003-01-01

102

Increase in the Serum Parathyroid Hormone Level During a Bisphosphonate Drug Holiday  

PubMed Central

After discontinuation of bisphosphonate therapy, an antiresorptive effect and antifracture protection persist for an undefined period. Patients are encouraged to continue calcium and vitamin D supplementation, during a bisphosphonate drug holiday. However, assessment of adequate calcium intake during the bisphosphonate drug holiday is difficult. Therefore, we measured the serum intact parathyroid hormone (PTH) level as a surrogate marker. A premenopausal woman discontinued bisphosphonate therapy, after 7.5 years of treatment. Two months later, blood calcium and phosphorus levels were normal, serum 25-hydroxyvitamin D level was 31.3 ng/mL, but serum PTH level had increased to 94.9 pg/mL. The elemental calcium supplement dose was increased to 600 mg/day, with no change in the cholecalciferol dose (400 IU). Her serum PTH levels decreased to 49.1 after 4 months and 32.9 pg/mL after 5 months. The serum PTH level may be helpful in assessing adequate calcium intake during a bisphosphonate drug holiday. PMID:25247160

Song, Yoon Kyung; Kim, Jeong Min; Park, Sun Jin

2014-01-01

103

Neuro-fuzzy technology as a predictor of parathyroid hormone level in hemodialysis patients.  

PubMed

Measuring the plasma parathyroid hormone (PTH) concentration is crucial to evaluate renal bone disease in patients with renal failure. Although frequent measurement is needed to avoid inadequate prescription of phosphate binders and vitamin D preparations, artificial intelligence can repeatedly perform the forecasting tasks and may be a satisfactory substitute for laboratory tests. Neuro-fuzzy technology represents a promising forecasting application in clinical medicine. We therefore constructed a coactive neuro-fuzzy inference system (CANFIS) to predict plasma PTH concentrations in hemodialysis patients. The CANFIS was constructed with clinical parameters (patient age, plasma albumin, calcium, phosphorus, alkaline phosphatase, and calcium-phosphorus product) from a cohort of hemodialysis patients, and plasma PTH concentration measured by radioimmunoassay (RIA) was the supervised outcome. The accuracy of the CANFIS was prospectively compared with RIA in another hospital. Plasma PTH concentrations measured by RIA and predicted by CANFIS were 179.04 +/- 38.18 ng/l and 179.34 +/- 37.76 ng/l, respectively (p = 0.15). The CANFIS was able to precisely estimate plasma PTH concentrations in hemodialysis patients. These results suggest that the neuro-fuzzy technology, based on limited clinical parameters, is an excellent alternative to RIA for accurately predicting plasma PTH concentration in hemodialysis patients. PMID:17202775

Chen, Chiou-An; Li, Yu-Chuan; Lin, Yuh-Feng; Yu, Fu-Chiu; Huang, Wei-Hsin; Chiu, Jainn-Shiun

2007-01-01

104

Sequence and activity of parathyroid hormone\\/parathyroid hormone-related protein receptor promoter region in human osteoblast-like cells  

Microsoft Academic Search

The parathyroid hormone (PTH)\\/PTH-related protein (PTHrP) receptor gene has been characterized in various species. The structure of its promoter and the regulation of its expression in human tissues have, however, not been clearly established yet. We characterized the region upstream of the PTH\\/PTHrP receptor gene and investigated its promoter activity in the human osteoblast-like SaOS-2 cells. In this region, three

Danielle Manen; Gaby Palmer; Jean-Philippe Bonjour; René Rizzoli

1998-01-01

105

Relaxant effects of parathyroid hormone and parathyroid hormone-related peptides on oviduct motility in birds and mammals: possible role of nitric oxide  

Microsoft Academic Search

Parathyroid hormone (PTH) and PTH-related peptides (PTHrP) have previously been shown to modulate the contractile state of numerous types of smooth muscle. The effects of N-terminal PTH and PTHrP on spontaneous in vitro contractility of oviducal smooth muscle using tissues from egg-laying Japanese quail (10–15h post ovulation), 4 and 9 days pregnant mouse uterus were investigated. Myometrial tissues from both

M. Francis; M. Arkle; L. Martin; T. M. Butler; M. C. Cruz; G. Opare-Aryee; C. G. Dacke; J. F. Brown

2003-01-01

106

Parathyroid hormone secretion by multiple distinct cell populations, a time dynamic mathematical model  

PubMed Central

Abstract The acute response of parathyroid hormone to perturbations in serum ionized calcium ([Ca2+]) is physiologically complex, and poorly understood. The literature provides numerous observations of quantitative and qualitative descriptions of parathyroid hormone (PTH) dynamics. We present a physiologically based mathematical model of PTH secretion constructed from mechanisms suggested in the literature, and validated against complex [Ca2+] clamping protocols from human data. The model is based on two assumptions. The first is that secretion is a fraction of cellular reserves, with the fraction being determined by the kinetics of [Ca2+] with its receptor. The second is that there are multiple distinct populations of parathyroid cells, with different secretory parameters. The steady state and transient PTH secretion responses of the model are in agreement with human experimental PTH responses to different hypocalcemia and hypercalcemia stimuli. This mathematical model suggests that a population of secreting cells is responsible for the PTH secretory dynamics observed experimentally. PMID:24744900

Pruett, William A.; Hester, Robert L.

2014-01-01

107

Synergistic Effect of Parathyroid Hormone and Growth Hormone on Trabecular and Cortical Bone Formation in Hypophysectomized Rats  

Microsoft Academic Search

Background\\/Aims: Growth hormone (GH) deficiency in pediatric patients results in short stature and osteopenia. We postulated that the GH and parathyroid hormone (PTH) combination would result in improvement in bone growth and bone formation. Methods: Forty hypophysectomized female rats at age 8 weeks were divided into hypophysectomy (HX), HX + PTH (62.5 ?g\\/kg, s.c. daily), HX + GH (3.33 mg\\/kg,

Maria Sarah N. Guevarra; James K. Yeh; Mariano Castro Magana; John F. Aloia

2010-01-01

108

Population based study on serum ionised calcium, serum parathyroid hormone, and blood pressure. The Tromso study  

Microsoft Academic Search

Objective: To study associations between serum ionised calcium, serum parathyroid hormone (PTH) and blood pressure. Design: A population based, cross-sectional study was used. Methods: Blood pressure, body mass index, serum ionised calcium and serum PTH were measured in 460 males and 486 females in the Tromsø study in 1994\\/1995. None were on medication for hypertension. The data were analysed with

Rolf Jorde; Kaare H Bønaa; Johan Sundsfjord

1999-01-01

109

Critical Role of Activating Transcription Factor 4 in the Anabolic Actions of Parathyroid Hormone in Bone  

Microsoft Academic Search

Parathyroid hormone (PTH) is a potent anabolic agent for the treatment of osteoporosis. However, its mechanism of action in osteoblast and bone is not well understood. In this study, we show that the anabolic actions of PTH in bone are severely impaired in both growing and adult ovariectomized mice lacking bone-related activating transcription factor 4 (ATF4). Our study demonstrates that

Shibing Yu; Renny T. Franceschi; Min Luo; Jie Fan; Di Jiang; Huiling Cao; Tae-Geon Kwon; Yumei Lai; Jian Zhang; Kenneth Patrene; Kurt Hankenson; G. David Roodman; Guozhi Xiao; Paul A. Bartell

2009-01-01

110

Original Full Length Article Effect of sequential treatments with alendronate, parathyroid hormone  

E-print Network

Original Full Length Article Effect of sequential treatments with alendronate, parathyroid hormone-resorptive and anabolic agents are often prescribed for the treatment of osteoporosis continuously or sequentially- ness. Treatment with PTH for 3 months caused the deposition of endocortical lamellar bone

Ritchie, Robert

111

SERUM MAGNESIUM CONCENTRATION IS AN INDEPENDENT PREDICTOR OF PARATHYROID HORMONE LEVELS IN PERITONEAL DIALYSIS PATIENTS  

Microsoft Academic Search

? ? ? ? ? Background: Parathyroid hormone (PTH) is a cardinal factor in the pathogenesis of bone disease in the dialysis population. The spectrum of renal osteodystrophy has been reported to have changed during the past years, and adynamic bone disease has emerged as the most com- mon bone disorder in these patients. Continuous ambu- latory peritoneal dialysis (CAPD)

Juan F. Navarro; Carmen Mora; Manuel Macia; Javier Garcia

112

Catch-up growth with normal parathyroid hormone levels in chronic renal failure  

Microsoft Academic Search

The optimum range for parathyroid hormone (PTH) levels in children with chronic renal failure (CRF) remains undefined. We aimed to determine growth velocity in children with CRF managed with normal PTH levels. We performed a retrospective case note review of 99 children (77 boys), with a glomerular filtration rate (GFR) 2, who had at least 2 years of 3-monthly follow-up. The

Simon Waller; Sarah Ledermann; Richard Trompeter; William van’t Hoff; Deborah Ridout; Lesley Rees

2003-01-01

113

Normocalcemia and persistent elevated serum concentrations of 1–84 parathyroid hormone after operation for sporadic parathyroid adenoma: evidence of increased morbidity from cardiovascular disease  

Microsoft Academic Search

Elevated serum concentrations of 1–84 parathyroid hormone (PTH) after operation for sporadic parathyroid adenoma have been\\u000a re-ported in previous studies, years after operation for primary hyperparathyroidism (pHPT). The cause and significance of\\u000a this finding have not been elucidated. Primary hyperparathyroidism was diagnosed in 195 patients from January 1987 to December\\u000a 1998. Operation for pHPT was performed in 124 patients. To

Henrik Vestergaard; Lars Østergaard Kristensen

2002-01-01

114

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

PubMed Central

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

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

2014-01-01

115

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

PubMed

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

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

2006-05-01

116

Relationship between serum intact parathyroid hormone concentrations and bone remodeling in type I osteoporosis: Evidence that skeletal sensitivity is increased  

Microsoft Academic Search

To define the role of parathyroid gland function in the pathophysiology of bone loss in type I (postmenopausal) osteoporosis, we measured serum intact parathyroid hormone (PTH) concentration by immunoradiometric assay (IRMA) and by multisite immunochemiluminometric assay (ICMA) in 63 postmenopausal osteoporotic women (PMOp) with vertebral compression fractures and in 75 age-comparable postmenopausal normal women (PMNl). Also, tetracycline-based histomorphometric indices in

M. A. Kotowicz; G. G. Klee; P. C. Kao; W. M. O'Fallon; S. F. Hodgson; S. L. Cedel; E. F. Eriksen; Daryl G. Gonchoroff; H. L. Judd; B. L. Riggs

1990-01-01

117

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

Microsoft Academic Search

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

Manuel Sánchez Regaña; Gemma Martín Ezquerra; Pablo Umbert Millet

2005-01-01

118

Intraoperative Parathyroid Hormone Monitoring Corroborates the Success of Parathyroidectomy in Children  

PubMed Central

Ob­jec­ti­ve: To assess the efficacy of intraoperative parathyroid hormone (PTH) monitoring in evaluating the outcome of parathyroidectomy in pediatric patients. Methods: Intraoperative PTH monitoring during parathyroidectomy was performed in five children (3M, 2F); three had parathyroid adenomas (single gland disease) and two had primary hyperplasia. One patient had undergone two previous surgical interventions to remove the parathyroid glands, but the PTH levels had remained high with persistence of symptoms. Immunoradiometric analysis was used for PTH measurements. Preoperative PTH values were obtained to monitor the baseline levels. Serum samples were collected 20 minutes after removal of the adenoma/parathyroid gland(s) and PTH levels were compared with preoperative values. Specimens were also confirmed by frozen sectional examination. Results: Mean age of the patients was 11 years (range: 3 months-16 years). Mean preoperative PTH values were 633.3±579 pg/mL (range: 143-1300 pg/mL). Intraoperative values decreased to 18.7±5.5 pg/mL (range: 8-27 pg/mL) following removal of the gland(s). Normal calcium levels were achieved with adequate management following surgery. One patient (with multiple surgeries and found to have an ectopic parathyroid gland) had hungry bone syndrome after the operation and was treated successfully. There were no major complications. All patients maintained normal calcium/phosphorus levels in the follow-up period, ranging from 2 to 5 years. Conclusion: An ectopic parathyroid gland or another undetected adenoma can be overlooked during surgery. Owing to the short life of the hormone, intraoperative PTH monitoring to determine PTH clearance proved to be a feasible marker for adequacy and safety of surgery and “cure”. PMID:25241609

Çelik, Ahmet; Divarc?, Emre; Dökümcü, Zafer; Ergün, Orkan; Özen, Samim; Gök?en, Damla; Darcan, ?ükran; Ertan, Ye?im

2014-01-01

119

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

PubMed

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

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

2013-09-01

120

Parathyroid hormone co-stimulation of hepatocyte proliferation is sensitive to protein kinase A and calcium channel inhibitors  

Microsoft Academic Search

Parathyroid hormone (PTH) mobilises calcium in the hepatocyte, an effect which is abolished by verapamil and staurosporine. In our study parathyroid hormone was shown to act additively to dHGF in inducing hepatocyte DNA synthesis. It is also shown that PTH induced the production of inositol 1,4,5 trisphosphate (IP3) andc-fos expression at early times in culture. Co-incubation of PTH and dHGF

George G. Skouteris

1996-01-01

121

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

Microsoft Academic Search

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

EDUARDO A SLATOPOLSKY; STEVEN K BURKE; MAUREEN A DILLON

1999-01-01

122

Effects of carbendazim on rat thyroid, parathyroid, pituitary and adrenal glands and their hormones.  

PubMed

The purpose of this study is to determine the effects of low and high dose of carbendazim on the level of certain hormones and endocrine glands (thyroid, parathyroid, adrenal and pituitary glands) of male rats. Carbendazim is a systemic fungicide with activity against a number of plant pathogens. In this study, daily doses of 0, 150, 300 and 600 mg/kg per day carbendazim were applied to male rats by gavage for 15 weeks. At the end of the experiment, T3, T4, TSH, ACTH and GH levels in rat serum were analysed. Thyroid, parathyroid, adrenal and pituitary glands of rats were taken. A significant increase was observed in serum T3 levels of the rats, which were exposed to 300 mg/kg per day carbendazim doses, compared to the serum T3 levels of the control group. There were no differences between the control and carbendazim-treated group of rats regarding serum TSH, T4, ACTH and growth hormone levels. This showed us that carbendazim caused histopathological damages in thyroid, parathyroid and adrenal glands of rats. No changes were observed in pituitary glands of treated rats. These results suggest that a high quantity of subchronic carbendazim exposure affects thyroid, parathyroid and adrenal glands. PMID:12099623

Barlas, N; Selmanoglu, G; Koçkaya, A; Songür, S

2002-04-01

123

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

Microsoft Academic Search

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

Narges Rashidi; Gregor B. Adams

2009-01-01

124

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

Microsoft Academic Search

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,

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

125

Developments in parathyroid hormone and related peptides as bone-formation agents  

Microsoft Academic Search

Osteoporosis is a major and growing healthcare concern. When administered by daily injection, parathyroid hormone (PTH) and its N-terminal fragments and analogs are potent bone-formation agents. Teriparatide, recombinant human PTH(1–34), is likely to be the first anabolic agent approved for treating osteoporosis, despite inducing osteosarcomas in rats. Native PTH and other PTH fragments and analogs are also in development. N-terminal

John Fox

2002-01-01

126

Synthetic parathyroid hormone-like protein (1–74) is anabolic for bone in vivo  

Microsoft Academic Search

Summary Parathyroid hormone-related protein (PTHRP) has recently been purified from human tumors associated with the syndrome of humoral hypercalcemia of malignancy. The gene encoding PTHRP has been cloned, and based on predicted amino acid sequence, polypeptides comprising the first 36 [36Tyr(1–36) PTHRP amide] and 74 [(1–74)PTHRP] amino acids have been synthesized. Human (h) PTHRP (1–36) and (1–74) are potent bone-resorbing

Eleanor C. Weir; Gordon Terwilliger; Leanordo Sartori; Karl L. Insogna

1992-01-01

127

The release profiles and bioactivity of parathyroid hormone from poly(lactic-co-glycolic acid) microspheres  

Microsoft Academic Search

Poly(lactic-co-glycolic acid) (PLGA) microspheres containing bovine serum albumin (BSA) or human parathyroid hormone (PTH)(1–34) were prepared using a double emulsion method with high encapsulation efficiency and controlled particle sizes. The microspheres were characterized with regard to their surface morphology, size, protein loading, degradation and release kinetics, and in vitro and in vivo assessments of biological activity of released PTH. PLGA5050

Guobao Wei; Glenda J. Pettway; Laurie K. McCauley; Peter X. Ma

2004-01-01

128

Relation of 25-hydroxyvitamin D and parathyroid hormone levels with metabolic syndrome among US adults  

Microsoft Academic Search

Objective: Previous research on the combined association of 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) with metabolic syndrome may have been limited by restricted age variability and a lack of representation of the general population. This study examined the combined association of 25(OH)D and PTH with Adult Treatment Panel III-defined MetSyn among a nationally representative sample of US adults. Design

Jared P Reis; Denise von Muhlen; Edgar R Miller III

2008-01-01

129

Serum intact parathyroid hormone levels in elderly Chinese females with hip fracture  

Microsoft Academic Search

Summary Serum intact parathyroid hormone (PTH), 25 hydroxyvitamin D(25OHD), 1,25 dihydroxyvitamin D (1,25(OH)2D), albumin, and ionized calcium were measured in 61 Chinese female patients with hip fracture and 61 control subjects. Hip fracture patients had low albumin, ionized calcium, and 250HD levels. Serum PTH and 1,25 (OH)2D values were not different between the two groups. We conclude that although 250HD

D. MacDonald; E. Lau; E. L. P. Chan; T. Mak; J. Woo; P. C. Leung; R. Swaminathan

1992-01-01

130

Effect of parathyroid hormone levels on carotid intima–media thickness after renal transplantation  

Microsoft Academic Search

Background:The present study aimed to investigate the intact parathyroid hormone (iPTH)–dependent evolution of common carotid intima–media thickness (CC IMT) in renal transplant recipients (RTR) within a 12-month follow-up, ie, before (E0) and 3 months (E3), 6 months (E6), and 12 months after renal transplantation (RTX).Methods:A total of 55 normotensive patients, aged 47 ± 1.7 years, underwent a RTX. The graft

Barbara Suwelack; Ulf Gerhardt; Jan Witta; Uta Hillebrandt; Helge Hohage

2001-01-01

131

Glycaemic control and serum intact parathyroid hormone levels in diabetic patients on haemodialysis therapy  

Microsoft Academic Search

Background. Osteodystrophy is one of the long-term haemodialysis complications, and in diabetic patients, it mainly occurs as an aplastic or low-turnover type due to their low serum intact parathyroid hormone (iPTH) levels. In the present study, we investigated the role of glycaemic control to the serum iPTH levels in diabetic haemodialysis patients. Methods. A total of 162 patients who had

Reiichi Murakami; Shuichi Murakami; Rumi Tsushima; Chiyuki Ueda; K yoko Mikami; Takanori Ebina; Ryuichiro Kumasaka; Norio Nakamura; Ken Okumura

132

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

Microsoft Academic Search

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

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

1987-01-01

133

Parathyroid hormone-related protein is a gravisensor in lung and bone cell biology  

Microsoft Academic Search

Parathyroid Hormone-related Protein (PTHrP) has been shown to be essential for the development and homeostatic regulation of lung and bone. Since both lung and bone structure and function are affected by microgravity, we hypothesized that 0 × g down-regulates PTHrP signaling. To test this hypothesis, we suspended lung and bone cells in the simulated microgravity environment of a Rotating Wall

J. S. Torday

2003-01-01

134

Bone density parathyroid hormone and 25-hydroxyvitamin D concentrations in middle aged women  

Microsoft Academic Search

OBJECTIVE--To examine the relation between bone density and indices of calcium metabolism including parathyroid hormone and 25-hydroxyvitamin D concentrations in middle aged women. DESIGN--A cross sectional study. SETTING AND SUBJECTS--138 women volunteers aged 45-65 with no known osteoporosis and unselected for disease status recruited for a dietary assessment study from the community using general practice registers. Volunteer rate was 20%.

K. T. Khaw; M. J. Sneyd; J. Compston

1992-01-01

135

Localization of parathyroid hormone-related protein in osteoclasts by in situ hybridization and immunohistochemistry  

Microsoft Academic Search

Using immunohistology with two specific antisera raised against N-terminal parathyroid hormone-related protein (PTHrP) and in situ hybridization (riboprobe to common coding exon), evidence is provided for the expression of PTHrP by mouse, rabbit, and human osteoclasts derived from several in vitro and in vivo sources. In cocultures of mouse bone marrow and calvarial cells treated with 1,25-dihydroxyvitamin D3, the generated

V. Kartsogiannis; N. Udagawa; K. W. Ng; T. J. Martin; J. M. Moseley; H. Zhou

1998-01-01

136

Growth hormone does not enhance the anabolic effect of human parathyroid hormone (1–34) on bone in aging multiparous and virgin rats  

Microsoft Academic Search

In humans, the progressive loss in skeletal bone mass with aging increases the risk of osteoporosis and bone fractures in the elderly. As parathyroid hormone (PTH) and growth hormone (GH) may both be anabolic in bone, we tested if the combination of these hormones would increase bone mass more than either agent alone in aging multiparous and virgin female rats.

Janet M. Hock; Richard J. Wood

1995-01-01

137

Bone anabolic effects of separate and combined therapy with growth hormone and parathyroid hormone on femoral neck in aged ovariectomized osteopenic rats  

Microsoft Academic Search

Previous studies have demonstrated that growth hormone (GH) has a marked anabolic effect on cortical bone and parathyroid hormone (PTH) has been shown to increase cancellous bone and cortical bone markedly in ovariectomized (OVX) rats. Most previous combination therapies used the bone anabolic agent (PTH) and the anti-resorptive agents. In this study, two bone anabolic hormones, GH and PTH, were

Liping Wang; Paul B. Orhii; Jameela Banu; Dike N. Kalu

2001-01-01

138

Signal transduction pathways mediating parathyroid hormone regulation of osteoblastic gene expression  

NASA Technical Reports Server (NTRS)

Parathyroid hormone (PTH) plays a central role in regulation of calcium metabolism. For example, excessive or inappropriate production of PTH or the related hormone, parathyroid hormone related protein (PTHrP), accounts for the majority of the causes of hypercalcemia. Both hormones act through the same receptor on the osteoblast to elicit enhanced bone resorption by the osteoclast. Thus, the osteoblast mediates the effect of PTH in the resorption process. In this process, PTH causes a change in the function and phenotype of the osteoblast from a cell involved in bone formation to one directing the process of bone resorption. In response to PTH, the osteoblast decreases collagen, alkaline phosphatase, and osteopontin expression and increases production of osteocalcin, cytokines, and neutral proteases. Many of these changes have been shown to be due to effects on mRNA abundance through either transcriptional or post-transcriptional mechanisms. However, the signal transduction pathway for the hormone to cause these changes is not completely elucidated in any case. Binding of PTH and PTHrP to their common receptor has been shown to result in activation of protein kinases A and C and increases in intracellular calcium. The latter has not been implicated in any changes in mRNA of osteoblastic genes. On the other hand activation of PKA can mimic all the effects of PTH; protein kinase C may be involved in some responses. We will discuss possible mechanisms linking PKA and PKC activation to changes in gene expression, particularly at the nuclear level.

Partridge, N. C.; Bloch, S. R.; Pearman, A. T.

1994-01-01

139

Intermittently administered parathyroid hormone 1–34 reverses bone loss and structural impairment in orchiectomized adult rats  

Microsoft Academic Search

Male osteoporosis is emerging as a central theme in bone research. As in females, hypogonadism appears as a principal risk factor in men that leads to bone loss and increased fracture incidence. Intermittently administered parathyroid hormone (PTH) reverses bone loss in sex hormone-deprived women and female animals and increases bone mass in elderly men and normal male animals. This study

Yankel Gabet; David Kohavi; Ralph Müller; Michael Chorev; Itai Bab

2005-01-01

140

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

NASA Astrophysics Data System (ADS)

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.

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

1995-03-01

141

Parathyroid hormone and growth hormone have additive or synergetic effect when used as intervention treatment in ovariectomized rats with established osteopenia  

Microsoft Academic Search

The severely osteoporotic human skeleton is characterized by thin cortices and a very fragile cancellous framework. To increase the biomechanical competence of such a skeleton, powerful anabolic agents are needed. The aim of the present study was to compare the effect of parathyroid hormone (PTH), growth hormone (GH) and combination treatment with PTH and GH in an aged, rat model

Li Mosekilde; L Tornvig; J. S Thomsen; P. B Orhii; M. J Banu; D. N Kalu

2000-01-01

142

Effects of separate and combined therapy with growth hormone and parathyroid hormone on lumbar vertebral bone in aged ovariectomized osteopenic rats  

Microsoft Academic Search

Previous studies have demonstrated that growth hormone (GH) has a marked anabolic effect on cortical bone, and parathyroid hormone (PTH) has been shown to increase cancellous bone markedly and cortical bone to some extent in ovariectomized (ovx) rats. Combined therapies mostly focused on combining a bone anabolic agent with an antiresorptive agent. The following study was carried out to examine

L Wang; P. B Orhii; J Banu; D. N Kalu

2001-01-01

143

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

SciTech Connect

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

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

2010-06-25

144

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

SciTech Connect

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

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

2008-08-07

145

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

PubMed

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-A 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-betaalpha 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. PMID:18375760

Pioszak, Augen A; Xu, H Eric

2008-04-01

146

Parathyroid Diseases and Animal Models  

PubMed Central

Circulating calcium and phosphate are tightly regulated by three hormones: the active form of vitamin D (1,25-dihydroxyvitamin D), fibroblast growth factor (FGF)-23, and parathyroid hormone (PTH). PTH acts to stimulate a rapid increment in serum calcium and has a crucial role in calcium homeostasis. Major target organs of PTH are kidney and bone. The oversecretion of the hormone results in hypercalcemia, caused by increased intestinal calcium absorption, reduced renal calcium clearance, and mobilization of calcium from bone in primary hyperparathyroidism. In chronic kidney disease, secondary hyperparathyroidism of uremia is observed in its early stages, and this finally develops into the autonomous secretion of PTH during maintenance hemodialysis. Receptors in parathyroid cells, such as the calcium-sensing receptor, vitamin D receptor, and FGF receptor (FGFR)-Klotho complex have crucial roles in the regulation of PTH secretion. Genes such as Cyclin D1, RET, MEN1, HRPT2, and CDKN1B have been identified in parathyroid diseases. Genetically engineered animals with these receptors and the associated genes have provided us with valuable information on the patho-physiology of parathyroid diseases. The application of these animal models is significant for the development of new therapies. PMID:22754549

Imanishi, Yasuo; Nagata, Yuki; Inaba, Masaaki

2012-01-01

147

Regulation of hormone-induced cyclic AMP response to parathyroid hormone and prostaglandin E 2 in cells cultured from human giant cell tumors of bone  

Microsoft Academic Search

Summary  Cells dispersed from human giant cell tumors of bone and grown in monolayer culture increase intracellular cyclic AMP (cAMP)\\u000a when incubated with parathyroid hormone (PTH) or prostaglandin E2 (PGE2). When cells are continuously exposed to PTH, cAMP levels increase acutely but then decrease rapidly to pretreatment values\\u000a despite continued presence of hormone or addition of new hormone. Preincubation of cells

Steven R. Goldring; Jean-Michel Dayer; Stephen M. Krane

1979-01-01

148

Parathyroid Hormone Receptor Directly Interacts with Dishevelled to Regulate ?-Catenin Signaling and Osteoclastogenesis*  

PubMed Central

Bone growth and remodeling depend upon the opposing rates of bone formation and resorption. These functions are regulated by intrinsic seven transmembrane-spanning receptors, the parathyroid hormone receptor (PTH1R) and frizzled (FZD), through their respective ligands, parathyroid hormone (PTH) and Wnt. FZD activation of canonical ?-catenin signaling requires the adapter protein Dishevelled (Dvl). We identified a Dvl-binding motif in the PTH1R. Here, we report that the PTH1R activates the ?-catenin pathway by directly recruiting Dvl, independent of Wnt or LRP5/6. PTH1R coimmunoprecipitated with Dvl. Deleting the carboxyl-terminal PTH1R PDZ-recognition domain did not abrogate PTH1R-Dvl interactions; nor did truncating the receptor at position 480. However, further deletion eliminating the putative Dvl recognition domain abolished PTH1R interactions with Dvl. PTH activated ?-catenin in a time- and concentration-dependent manner and translocated ?-catenin to the nucleus. ?-Catenin activation was inhibited by Dvl2 dominant negatives and by short hairpin RNA sequences targeted against Dvl2. PTH-induced osteoclastogenesis was also inhibited by Dvl2 dominant negative mutants. These findings demonstrate that G protein-coupled receptors other than FZD directly activate ?-catenin signaling, thereby mimicking many of the functions of the canonical Wnt-FZD pathway. The distinct modes whereby FZD and PTH1R activate ?-catenin control convergent or divergent effects on osteoblast differentiation, and osteoclastogenesis may arise from PTH1R-induced second messenger phosphorylation. PMID:20212039

Romero, Guillermo; Sneddon, W. Bruce; Yang, Yanmei; Wheeler, David; Blair, Harry C.; Friedman, Peter A.

2010-01-01

149

?-Arrestin-biased signaling of PTH analogs of the type 1 parathyroid hormone receptor.  

PubMed

Parathyroid hormone (PTH) is an anabolic agent that mediates bone formation through activation of the G?(s)-, G?(q)- and ?-arrestin-coupled parathyroid hormone receptor type 1 (PTH1R). Pharmacological evidence based on the effect of PTH(7-34), a PTH derivative that is said to preferentially activate ?-arrestin signaling through PTH1R, suggests that PTH1R-activated ?-arrestin signaling mediates anabolic effects on bone. Here, we performed a thorough evaluation of PTH(7-34) signaling behaviour using quantitative assays for ?-arrestin recruitment, G?(s)- and G?(q)-signaling. We found that PTH(7-34) inhibited PTH-induced cAMP accumulation, but was unable to induce ?-arrestin recruitment, PTH1R internalization and ERK1/2 phosphorylation in HEK293, CHO and U2OS cells. Thus, the ?-arrestin bias of PTH(7-34) is not apparent in every cell type examined, suggesting that correlating in vivo effects of PTH(7-34) to in vitro pharmacology should be done with caution. PMID:23159578

van der Lee, Miranda M C; Verkaar, Folkert; Wat, Jesse W Y; van Offenbeek, Jody; Timmerman, Martijn; Voorneveld, Lonneke; van Lith, Lambertus H C J; Zaman, Guido J R

2013-02-01

150

Associations of Sun Exposure with 25-Hydroxyvitamin D and Parathyroid Hormone Levels in a Cohort of Hypertensive Patients: The Graz Endocrine Causes of Hypertension (GECOH) Study  

PubMed Central

Sunlight-induced vitamin D, synthesis in the skin is the major source of vitamin D, but data on the relationship of sun-related behaviour with vitamin D and parathyroid hormone (PTH) levels are relatively sparse. We evaluated whether habitual sun exposure is associated with 25-hydroxyvitamin D (25[OH]D) and PTH levels and whether there exist seasonal variations. We examined 111 hypertensive patients in Austria (latitude 47°?N). Frequent sunbathing at home and outdoor sports were associated with higher 25(OH)D levels (P < 0.05 for both). Red or blond scalp hair as a child, memory of sunburns, preferring sunbathing, frequent stays on the beach or in open-air pools, and solarium use were associated with lower PTH levels (P < 0.05 for all). Multiple linear regression analyses including age, sex, and body mass index showed that sun exposure score was significantly associated with 25(OH)D (beta coefficient = 0.27; P = 0.004) and by trend with PTH (beta coefficient = ?0.16; P = 0.09). These associations were more prominent in summer in which 25(OH)D levels were significantly higher compared to winter. Translation of these findings into recommendations for the prevention and treatment of vitamin D deficiency remains a challenge for the future. PMID:22518130

Pilz, Stefan; Kienreich, Katharina; Stückler, Daniel; Meinitzer, Andreas; Tomaschitz, Andreas

2012-01-01

151

Vitamin D Therapy of Osteoporosis: Plain Vitamin D Therapy Versus Active Vitamin D Analog (D-Hormone) Therapy  

Microsoft Academic Search

.   Normal intestinal calcium (Ca) absorption is an essential feature of bone homeostasis. As with many other organ systems,\\u000a intestinal Ca absorption declines with aging, and this is one pathological factor that has been identified as a cause of senile\\u000a osteoporosis in the elderly. This abnormality leads to secondary hyperparathyroidism, which is characterized by high serum\\u000a parathyroid hormone (PTH) and

K.-H. W. Lau; D. J. Baylink

1999-01-01

152

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

PubMed

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

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

2015-03-01

153

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

Microsoft Academic Search

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

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

1995-01-01

154

Plasma levels of parathyroid hormone that induce anabolic effects in bone of ovariectomized rats can be achieved by stimulation of endogenous hormone secretion  

Microsoft Academic Search

Parathyroid hormone (PTH) administration increases bone mass in normal and osteopenic animals. However, this treatment currently requires the daily injection of large amounts of PTH, and the relationship of these doses to plasma levels of PTH that are achievable physiologically is unknown. We determined in ovariectomized (ovx) rats: 1) the plasma PTH levels that occur after the subcutaneous injection of

J. Fox; M. A. Miller; G. B. Stroup; E. F. Nemeth; S. C. Miller

1997-01-01

155

The dual face of parathyroid hormone and prostaglandins in the osteoimmune system.  

PubMed

The microenvironment of bone marrow, an extraordinarily heterogeneous and dynamic system, is populated by bone and immune cells, and its functional dimension has been at the forefront of recent studies in the field of osteoimmunology. The interaction of both marrow niches supports self-renewal, differentiation, and homing of the hematopoietic stem cells and provides the essential regulatory molecules for osteoblast and osteoclast homeostasis. Impaired signaling within the niches results in a pathological tableau and enhances disease, including osteoporosis and arthritis, or the rejection of hematopoietic stem cell transplants. Discovering the anabolic players that control these mechanisms has become warranted. In this review, we focus on parathyroid hormone (PTH) and prostaglandins (PGs), potent molecular mediators, both of which carry out a multitude of functions, particularly in bone lining cells and T cells. These two regulators proved to be promising therapeutic agents when strictly clinical protocols on dose treatments were applied. PMID:24045870

Agas, Dimitrios; Marchetti, Luigi; Capitani, Melania; Sabbieti, Maria Giovanna

2013-11-15

156

Hypercalcemia upon recurrence of renal cell carcinoma producing parathyroid hormone-related protein.  

PubMed

We established a new renal carcinoma cell line that produces parathyroid hormone-related protein (PTHrP) and interleukin-6 in culture. The cellular production of PTHrP was confirmed by Northern blot analysis and immunofluorescence examination. Bone and lung metastases occurred simultaneously 3.5 years after surgery. The patient did not show hypercalcemia at this time, despite the presence of multiple osteolytic metastases. About 7 months after bone metastasis was first shown, serum PTHrP was detected by means of an immunoradiometric assay and the calcium level was found to be elevated to 3.29 mmol/l. The hypercalcemia was successfully controlled by i.v. administration of bisphosphonates. PMID:12775288

Ueno, Munehisa; Tokonabe, Shigeki; Kuroda, Isao; Tsukamoto, Takuji; Deguchi, Nobuhiro

2003-01-01

157

Evolution of Parathyroid Hormone Receptor Family and Their Ligands in Vertebrate  

PubMed Central

The presence of the parathyroid hormones in vertebrates, including PTH, PTH-related peptide (PTHrP), and tuberoinfundibular peptide of 39 residues (TIP39), has been proposed to be the result of two rounds of whole genome duplication in the beginning of vertebrate diversification. Bioinformatics analyses, in particular chromosomal synteny study and the characterization of the PTH ligands and their receptors from various vertebrate species, provide evidence that strongly supports this hypothesis. In this mini-review, we summarize recent advances in studies regarding the molecular evolution and physiology of the PTH ligands and their receptors, with particular focus on non-mammalian vertebrates. In summary, the PTH family of peptides probably predates early vertebrate evolution, indicating a more ancient existence as well as a function of these peptides in invertebrates. PMID:25806022

On, Jason S. W.; Chow, Billy K. C.; Lee, Leo T. O.

2015-01-01

158

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

SciTech Connect

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

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

1985-01-01

159

Mass Spectrometric Immunoassay for Parathyroid Hormone Related Protein (PTHrP)  

SciTech Connect

Many cancers, including prostate, breast and lung express parathyroid hormone related protein (PTHrP). Despite the common tumor overexpression of PTHrP, serum levels of PTHrP are not commonly elevated in affected patients. They postulate that the reasons for the discrepancy between tissue and serum measurements of PTHrP are the inadequate sensitivity and specificity of current PTHrP serum assays. To improve the clinical value of PTHrP serum assays for the cancer patient, they are developing a new generation of novel and ultrasensitive PTHrP serum immunoassays based on immunoaffinity purification, nanospray liquid chromatography tandem mass spectrometry (LC/MS/MS) and accelerator mass spectrometry (AMS).

Zheng, K.; Rivera, J.D.; Vogel, J.S.; Buchholz, B.A.; Burton, D.W.; Deftos, L.J.; Herold, D.A.; Fitzgerald, R.L.

2000-06-16

160

Calcium transport in canine renal basolateral membrane vesicles. Effects of parathyroid hormone.  

PubMed Central

The effects of parathyroid hormone were studied on Ca2+ fluxes in canine renal proximal tubular basolateral membrane vesicles (BLMV). Efflux of Ca2+ from preloaded BLMV was found to be stimulated by an external Na+ gradient, and this was inhibited by the Na+ ionophore, monensin, and enhanced by intravesicular negative electrical potentials, which indicated electrogenic Na+/Ca2+ exchange activity. There was a Na+ gradient independent Ca2+ flux, but membrane binding of Ca2+ was excluded from contributing to the Na+ gradient-dependent efflux. The Na+ gradient-dependent flux of Ca2+ was very rapid, and even 2- and 5-s points may not fully represent absolute initial rates. It was saturable with respect to the interaction of Ca2+ and Na+ with an apparent (5 s) Km for Na+-dependent Ca2+ uptake of 10 microM, and an apparent (5 s) Vmax of 0.33 nmol/mg protein per 5 s. The Na+ concentration that yielded half maximal Ca2+ efflux (2 s) was 11 mM, and the Hill coefficient was two or greater. Both Na+ gradient dependent and independent Ca2+ efflux were decreased in BLMV prepared from kidneys of thyroparathyroidectomized (TPTX) dogs, and both were stimulated by parathyroid hormone (PTH) infusion to TPTX dogs. BLMV from TPTX dogs exhibited significantly reduced maximal stimulation of Na+ gradient-dependent Ca2+ uptake with an apparent (5 s) Vmax of 0.23 nmol/mg protein per 5 s, but the apparent Km was 8 microM, which was unchanged from normal. The Na+ gradient independent Ca2+ uptake was also reduced in BLMV from TPTX dogs compared with normal. Thus, PTH stimulated both Na+/Ca2+ exchange activity and Na+ independent Ca2+ flux. In vivo, the latter could result in an elevation of cytosolic Ca2+ by PTH, and this might contribute to the observed decrease in solute transport in the proximal tubule. Images PMID:3988932

Scoble, J E; Mills, S; Hruska, K A

1985-01-01

161

Synthetic parathyroid hormone-like protein (1-74) is anabolic for bone in vivo.  

PubMed

Parathyroid hormone-related protein (PTHRP) has recently been purified from human tumors associated with the syndrome of humoral hypercalcemia of malignancy. The gene encoding PTHRP has been cloned, and based on predicted amino acid sequence, polypeptides comprising the first 36 [36Tyr(1-36) PTHRP amide] and 74 [(1-74)PTHRP] amino acids have been synthesized. Human (h) PTHRP (1-36) and (1-74) are potent bone-resorbing agents, and are catabolic for bone in vivo when given continuously at high doses. Bovine parathyroid hormone (bPTH) (1-34) is also catabolic for bone at high dose levels, but when given in low doses for weeks to months, it is anabolic. Although PTHRP possess several PTH-like properties in bone, hPTHRP (1-34) is reported to be only weakly anabolic in vivo. As polypeptide length influences PTHRP action, we evaluated hPTHRP(1-74) as an anabolic agent for bone in vivo. Twenty-four 4-week-old male Sprague-Dawley rats were given daily subcutaneous injections of hPTHRP(1-74) (1 and 2 nmol/100 g body weight, bw), bPTH(1-34) (4 nmol/100 g bw) or vehicle. Rats were sacrificed on day 12, and serum calcium, phosphorus, and 1,25 dihydroxyvitamin D and femoral bone dry weight, calcium content, and hydroxyproline content were measured. Serum calcium and phosphorus were equivalent in all groups. A significant increase in dry bone weight was observed in both PTHRP-treated groups compared with controls. PTHRP also caused a significant, dose-dependent increase in bone calcium and hydroxyproline content. Results of these studies indicate that PTHRP (1-74) is anabolic for bone in vivo when administered at low-dosage levels for a prolonged period. PMID:1393774

Weir, E C; Terwilliger, G; Sartori, L; Insogna, K L

1992-07-01

162

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

NASA Technical Reports Server (NTRS)

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

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

2002-01-01

163

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

SciTech Connect

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.

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

2009-12-01

164

Structural basis for parathyroid hormone-related protein binding to the parathyroid hormone receptor and design of conformation-selective peptides.  

PubMed

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. PMID:19674967

Pioszak, Augen A; Parker, Naomi R; Gardella, Thomas J; Xu, H Eric

2009-10-01

165

Absence of response to human parathyroid hormone in athymic mice grafted with human parathyroid adenoma, hyperplasia or parathyroid cells maintained in culture.  

PubMed

In athymic mice we have developed a model of long-term human PTH hypersecretion, using xenotransplantation of respectively parathyroid gland fragments obtained from patients with primary (primary) or secondary (secondary) uremic hyperparathyroidism (HPT), and parathyroid cells maintained in culture from patients with secondary uremic HPT. Both grafted parathyroid tissue fragments and cultured cells induced prolonged and marked secretion of human intact PTH (iPTH) in nude mice. Despite extremely high plasma iPTH levels, hypercalcemia or hypophosphatemia was not observed. Moreover, PTH secretion was not significantly modified by low-calcium, high-phosphate diet for 3 weeks. Four mice which had a mean plasma human iPTH level of 237+/-152 pg/ml for more than 9 months and 4 age-matched, sham-grafted control mice with undetectable human iPTH levels underwent bone histomorphometry examination. No difference was found between the two groups with respect to active bone resorption surface or number of osteoclasts/mm2. We hypothesize that the characteristic deficit of T cell function and of cytokine and growth factor production may protect nude mice with chronic hypersecretion of human PTH from hypercalcemia and bone lesions. We suggest that this strain of mice could be used for better understanding the relationship between cytokines and bone turnover. PMID:10882144

Hory, B G; Roussanne, M C; Rostand, S; Bourdeau, A; Drüeke, T B; Gogusev, J

2000-05-01

166

Opuntia humifusa Supplementation Increased Bone Density by Regulating Parathyroid Hormone and Osteocalcin in Male Growing Rats  

PubMed Central

We investigated the effect of Opuntia humifusa (O. humifusa) supplementation on bone density and related hormone secretion in growing male rats. Sixteen six-week-old male Sprague-Dawley rats were randomly divided into two groups; control diet group (CG, n = 8), and experimental diet group (EG, n = 8). The rats in the CG were given a control diet and those in the EG were given 5% O. humifusa added to the control diet for eight weeks. The serum OC level of the EG was significantly higher than that of the CG, and the serum parathyroid hormone (PTH) level of EG was significantly lower than that of the CG. In addition, the femoral and tibial BMD of the EG were significantly higher values than those of the CG, and the tibial BMC of the EG was significantly higher than that of the CG. These results suggest that O. humifusa supplementation has a positive effect on bone density by suppressing PTH and increasing the OC level in growing male rats. PMID:22837661

Kang, Junyong; Park, Jinho; Choi, Seong Hee; Igawa, Shoji; Song, Youngju

2012-01-01

167

Prediction of target range of intact parathyroid hormone in hemodialysis patients with artificial neural network.  

PubMed

The application of artificial neural network (ANN) to predict outcome and explore potential relationships among clinical data is increasing being used in many clinical scenarios. The aim of this study was to validate whether an ANN is a useful tool for predicting the target range of plasma intact parathyroid hormone (iPTH) concentration in hemodialysis patients. An ANN was constructed with input variables collected retrospectively from an internal validation group (n = 129) of hemodialysis patients. Plasma iPTH was the dichotomous outcome variable, either target group (150 ng/Lhormone >300 ng/L). After internal validation, the ANN was prospectively tested in an external validation group (n = 32) of hemodialysis patients. The final ANN was a multilayer perceptron network with six predictors including age, diabetes, hypertension, and blood biochemistries (hemoglobin, albumin, calcium). The externally validated ANN provided excellent discrimination as appraised by area under the receiver operating characteristic curve (0.83 +/- 0.11, p = 0.003). The Hosmer-Lemeshow statistic was 5.02 (p= 0.08 > 0.05) which represented a good-fit calibration. These results suggest that an ANN, which is based on limited clinical data, is able to accurately forecast the target range of plasma iPTH concentration in hemodialysis patients. PMID:16839639

Wang, Yuh-Feng; Hu, Tsung-Ming; Wu, Chia-Chao; Yu, Fu-Chiu; Fu, Chao-Ming; Lin, Shih-Hua; Huang, Wei-Hsin; Chiu, Jainn-Shiun

2006-08-01

168

Developments in parathyroid hormone and related peptides as bone-formation agents.  

PubMed

Osteoporosis is a major and growing healthcare concern. When administered by daily injection, parathyroid hormone (PTH) and its N-terminal fragments and analogs are potent bone-formation agents. Teriparatide, recombinant human PTH(1-34), is likely to be the first anabolic agent approved for treating osteoporosis, despite inducing osteosarcomas in rats. Native PTH and other PTH fragments and analogs are also in development. N-terminal fragments sometimes differ in activity from the native hormone, however, and the C-terminal region of PTH, acting through a receptor different from the classical PTH-1 receptor, initiates a variety of distinct biological activities. In particular, the C-terminal region of PTH, by promoting bone-cell apoptosis, may be important in opposing the anti-apoptotic effects of teriparatide in these cells, thereby maintaining normal bone-cell turnover. Because of these differences, care must be taken to consider the effects of native PTH and N-terminal PTH fragments and analogs separately. PMID:12020480

Fox, John

2002-06-01

169

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

PubMed Central

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

2012-01-01

170

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

SciTech Connect

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.

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

1991-02-01

171

Differential Regulation of Osteoblast Activity by Th Cell Subsets Mediated by Parathyroid Hormone and IFN-?1  

PubMed Central

Bone loss is a typical pathological feature of chronic inflammatory bone diseases including rheumatoid arthritis, in which CD4 effector T cells play critical roles. We found that activated mouse Th2 and not Th1 cells produced the parathyroid hormone (PTH). Unlike in the parathyroid cells, PTH expression in Th2 cells was not regulated by the fluctuation of calcium level, but rather it required the full activation of the T cells. Although PTH was expressed in immature Th2 cells, and its receptor was transiently expressed during Th1 and Th2 cell differentiation, PTH did not significantly affect the outcome of the differentiation. In primary osteoblasts cultured in Th2 cell condition medium, the alkaline phosphatase (ALP) activity was maintained at a basal level. However, antagonizing PTH in the condition medium resulted in a significant reduction of the ALP activity. These results demonstrated an important role of the Th2 cell-derived PTH in maintaining the bone-forming activity of the osteoblasts under inflammatory conditions. In osteoblasts cultured in the Th1 cell condition medium, the ALP activity was significantly suppressed. Neutralizing IFN-? alleviated the suppression. Conversely, treatment of osteoblasts with IFN-? suppressed the ALP activity. Unlike ALP, expression of the major bone matrix proteins by the osteoblasts was only minimally affected by either Th1 or Th2 cytokine environment. In addition, the Th2 cytokine environment also regulated to expression of receptor activator of NF-? B ligand and osteoprotegerin through both PTH-dependent and -independent mechanisms. Our study therefore identified new regulatory events in bone remodeling under inflammatory conditions. PMID:16339569

Young, Nathan; Mikhalkevich, Natallia; Yan, Ying; Chen, Di; Zheng, Wei-ping

2009-01-01

172

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

SciTech Connect

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+

Flanagan, J.L.

1990-01-01

173

A comparison of parathyroid hormone-related protein (1-36) and parathyroid hormone (1-34) on markers of bone turnover and bone density in postmenopausal women: the PrOP study.  

PubMed

Parathyroid hormone-related protein (PTHrP)(1-36) increases lumbar spine (LS) bone mineral density (BMD), acting as an anabolic agent when injected intermittently, but it has not been directly compared with parathyroid hormone (PTH)(1-34). We performed a 3-month randomized, prospective study in 105 postmenopausal women with low bone density or osteoporosis, comparing daily subcutaneous injections of PTHrP(1-36) to PTH(1-34). Thirty-five women were randomized to each of three groups: PTHrP(1-36) 400?µg/day; PTHrP(1-36) 600?µg/day; and PTH(1-34) 20?µg/day. The primary outcome measures were changes in amino-terminal telopeptides of procollagen 1 (PINP) and carboxy-terminal telopeptides of collagen 1 (CTX). Secondary measures included safety parameters, 1,25(OH)2 vitamin D, and BMD. The increase in bone resorption (CTX) by PTH(1-34) (92%) (p?

Horwitz, Mara J; Augustine, Marilyn; Khan, Leila; Kahn, Leila; Martin, Emily; Oakley, Christine C; Carneiro, Raquel M; Tedesco, Mary Beth; Laslavic, Angela; Sereika, Susan M; Bisello, Alessandro; Garcia-Ocaña, Adolfo; Gundberg, Caren M; Cauley, Jane A; Stewart, Andrew F

2013-11-01

174

Expression of parathyroid hormone (PTH)\\/PTH-related peptide receptor messenger ribonucleic acid in mice hair cycle  

Microsoft Academic Search

There is increasing evidence that parathyroid hormone (PTH) and PTH-related peptide (PTHrP) are involved in normal skin cell growth, influence the proliferation and differentiation of the epidermis and hair follicle. PTHrP and PTH\\/PTHrP receptor show prominent cutaneous expression, may exert important paracrine and\\/or autocrine functions. The expression of PTH\\/PTHrP receptor in different stages of hair cycle is unknown. Therefore, we

Ying Wang; Shu-xia Yang; Ping Tu; Bo Zhang; Sheng-qing Ma

2002-01-01

175

Parathyroid hormone: A novel tool for treating bone marrow depletion in cancer patients caused by chemotherapeutic drugs and ionizing radiation  

Microsoft Academic Search

Between 1958 and the late 1970s it was learned that PTH (the parathyroid hormone) could directly stimulate the initiation of DNA replication by murine CFU-S (colony-forming unit-spleen) cells via cyclic AMP, stimulate the proliferation of normal and X-irradiated murine and rat bone marrow cells, control hematopoiesis, and increase the survival of X-irradiated mice and rats when injected any time between

James F. Whitfield

2006-01-01

176

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

Microsoft Academic Search

Parathyroid hormone (PTH) is a potent anabolic agent for bone, but the mechanism(s) by which it works remains imperfectly understood. Previous studies have indicated that PTH stimulates insulin-like growth factor (IGF) I production, but it remains uncertain whether IGF-I mediates some or all of the skeletal actions of PTH. To address this question, we examined the skeletal response to PTH

D D Bikle; T Sakata; C Leary; H Elalieh; D Ginzinger; C J Rosen; W Beamer; S Majumdar; B P Halloran

2002-01-01

177

Temporally regulated overexpression of parathyroid hormone-related protein in the mammary gland reveals distinct fetal and pubertal phenotypes  

Microsoft Academic Search

We have previously demonstrated that overexpression of parathyroid hormone-related protein (PTHrP) in the mammary glands of transgenic mice results in defects in ductal elongation and branching during puberty and in lobuloalveolar development during pregnancy. In ad- dition, we have shown that PTHrP is necessary for the formation of the initial ductal tree during embryonic mammary development. In order to examine

M E Dunbar; P Dann; C W Brown; J Van Houton; B Dreyer; W P Philbrick; J J Wysolmerski

2001-01-01

178

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

Microsoft Academic Search

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

S. J. Gallacher; T. Dixon

2010-01-01

179

What parathyroid hormone levels should we aim for in children with stage 5 chronic kidney disease; what is the evidence?  

Microsoft Academic Search

The bone disease that occurs as a result of chronic kidney disease (CKD) is not only debilitating but also linked to poor\\u000a growth and cardiovascular disease. It is suspected that abnormal bone turnover is the main culprit for these poor outcomes.\\u000a Plasma parathyroid hormone (PTH) levels are used as a surrogate marker of bone turnover, and there is a small

Lesley Rees

2008-01-01

180

Studies on in vivo and in vitro release of intact parathyroid hormone using a new two-site immunochemiluminometric assay  

Microsoft Academic Search

Basal parathyroid hormone (PTH) levels measured by a chemiluminescent immunoassay for intact PTH showed good discrimination between normal, n=82 (1.2–9.4 pmol\\/l), and hyperparathyroid subjects, n=55 (9–200 pmol\\/l). In malignant hypercalcemia, all PTH levels were within the normal range or suppressed (0.8–5.2 pmol\\/l). Dynamic studies of PTH release in response to intramuscular salmon calcitonin (100 u) showed no significant rise out

J. Paul Aston; Malcolm H. Wheeler; Richard C. Brown; Ian R. Curley; J. Stuart Woodhead

1988-01-01

181

Effects of intermittent versus continuous parathyroid hormone administration on condylar chondrocyte proliferation and differentiation  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer Different PTH administration exerts different effects on condylar chondrocyte. Black-Right-Pointing-Pointer Intermittent PTH administration suppresses condylar chondrocyte proliferation. Black-Right-Pointing-Pointer Continuous PTH administration maintains condylar chondrocyte proliferating. Black-Right-Pointing-Pointer Intermittent PTH administration enhances condylar chondrocyte differentiation. -- Abstract: Endochondral ossification is a complex process involving chondrogenesis and osteogenesis regulated by many hormones and growth factors. Parathyroid hormone (PTH), one of the key hormones regulating bone metabolism, promotes osteoblast differentiation and osteogenesis by intermittent administration, whereas continuous PTH administration inhibits bone formation. However, the effects of PTH on chondrocyte proliferation and differentiation are still unclear. In this study, intermittent PTH administration presented enhanced effects on condylar chondrocyte differentiation and bone formation, as demonstrated by increased mineral nodule formation and alkaline phosphatase (ALP) activity, up-regulated runt-related transcription factor 2 (RUNX2), ALP, collagen type X (COL10a1), collagen type I (COL1a1), osteocalcin (OCN), bone sialoprotein (BSP), bone morphogenetic protein 2 (BMP2) and osterix (OSX) mRNA and/or protein expression. On the contrary, continuous PTH administration promoted condylar chondrocyte proliferation and suppressed its differentiation, as demonstrated by up-regulated collagen type II (COL2a1) mRNA expression, reduced mineral nodule formation and down-regulated expression of the mRNAs and/or proteins mentioned above. Our data suggest that PTH can regulate condylar chondrocyte proliferation and differentiation, depending on the type of PTH administration. These results provide new insight into the effects of PTH on condylar chondrocytes and new evidence for using local PTH administration to cure mandibular asymmetry.

Liu, Qi; Wan, Qilong; Yang, Rongtao; Zhou, Haihua [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China)] [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China); Li, Zubing, E-mail: lizubing0827@163.com [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China) [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China); Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China)

2012-07-20

182

21 CFR 101.72 - Health claims: calcium, vitamin D, and osteoporosis.  

Code of Federal Regulations, 2010 CFR

...skeletal maturity. Vitamin D is required for normal absorption of calcium and to prevent the occurrence of high serum parathyroid hormone (PTH) concentration, which stimulates mobilization of calcium from the skeleton and can lower bone mass....

2010-04-01

183

21 CFR 101.72 - Health claims: calcium, vitamin D, and osteoporosis.  

Code of Federal Regulations, 2013 CFR

...skeletal maturity. Vitamin D is required for normal absorption of calcium and to prevent the occurrence of high serum parathyroid hormone (PTH) concentration, which stimulates mobilization of calcium from the skeleton and can lower bone mass....

2013-04-01

184

21 CFR 101.72 - Health claims: calcium, vitamin D, and osteoporosis.  

Code of Federal Regulations, 2014 CFR

...skeletal maturity. Vitamin D is required for normal absorption of calcium and to prevent the occurrence of high serum parathyroid hormone (PTH) concentration, which stimulates mobilization of calcium from the skeleton and can lower bone mass....

2014-04-01

185

21 CFR 101.72 - Health claims: calcium, vitamin D, and osteoporosis.  

Code of Federal Regulations, 2011 CFR

...skeletal maturity. Vitamin D is required for normal absorption of calcium and to prevent the occurrence of high serum parathyroid hormone (PTH) concentration, which stimulates mobilization of calcium from the skeleton and can lower bone mass....

2011-04-01

186

21 CFR 101.72 - Health claims: calcium, vitamin D, and osteoporosis.  

Code of Federal Regulations, 2012 CFR

...skeletal maturity. Vitamin D is required for normal absorption of calcium and to prevent the occurrence of high serum parathyroid hormone (PTH) concentration, which stimulates mobilization of calcium from the skeleton and can lower bone mass....

2012-04-01

187

Parathyroid hormone levels in pubertal uremic adolescents treated with growth hormone  

Microsoft Academic Search

We have previously described severe hyperparathyroidism during the pubertal growth spurt in three uremic adolescents treated with recombinant human growth hormone (rhGH). Here we investigate the possible role of puberty in the genesis of hyperparathyroidism during rhGH treatment of a large cohort of patients. Data from 67 uremic patients treated with rhGH from five Italian pediatric nephrology centers were retrospectively

Stefano Picca; Marco Cappa; Chiara Martinez; Seyoum Ido Moges; John Osborn; Francesco Perfumo; Gianluigi Ardissino; Roberto Bonaudo; Giovanni Montini; Gianfranco Rizzoni

2004-01-01

188

Divergent effects of forskolin on 3?,5? cyclic adenosine monophosphate production and parathyroid hormone secretion  

Microsoft Academic Search

Summary  Forskolin, a diterpene which directly stimulates adenylate cyclase, markedly stimulated cAMP production in intact rat parathyroid\\u000a glands and dispersed cells from hyperplastic and adenomatous human parathyroid tissues. Stimulation of cAMP production in\\u000a human parathyroid adenomas occurred as early as 2 min and continued for at least 2 h; furthermore, a dose-response relationship\\u000a was observed, with a maximal 80-fold cAMP response

Larry K. Cantley; Drusilla L. Scott; Cary W. Cooper; Darien D. Mahaffee; George S. Leight; Colin G. Thomas; David A. Ontjes

1984-01-01

189

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

PubMed

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

Zhang, Hong; Liang, Lingyun; Xie, Zhongjian

2014-11-01

190

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

PubMed

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

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

1989-06-01

191

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

PubMed Central

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

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

2014-01-01

192

Is Intraoperative Parathyroid Hormone Testing in Patients with Renal Insufficiency Undergoing Parathyroidectomy for Primary Hyperparathyroidism Accurate?  

PubMed Central

Background Our aim was to determine whether chronic renal insufficiency (CRI) impacts intraoperative parathyroid hormone (ioPTH) monitoring during parathyroidectomy. We hypothesized that ioPTH monitoring in patients with chronic CRI would show slower decline, but still accurately predict cure. Methods A retrospective review of patients with primary hyperparathyroidism who underwent curative single adenoma parathyroidectomy. The percentage of patients reaching 50% decline of ioPTH was compared between groups stratified by renal function. Results Between 2000 and 2013, 950 patients met inclusion criteria. At five minutes, 66% of patients with CRI met curative criteria vs. 77% of normal renal function patients (p=0.001). At ten minutes, 89% vs. 92% met criteria (p=0.073), and by fifteen minutes, the gap narrowed to 95% vs. 97% (p=0.142). Conclusions Despite CRI patients with primary hyperparathyroidism having slower ioPTH decline after curative parathyroidectomy, 95% met ioPTH criteria by 15 minutes. Standard ioPTH criteria can be used with CRI patients. PMID:25556028

Sohn, Jonathan A.; Oltmann, Sarah C.; Schneider, David F.; Sippel, Rebecca S.; Chen, Herbert; Elfenbein, Dawn M.

2015-01-01

193

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

PubMed

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

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

2014-11-26

194

Proximal tubule reabsorption after hyperoncotic albumin infusion. Role of parathyroid hormone and dissociation from plasma volume.  

PubMed

Preferential expansion of the plasma volume by infusion of salt-poor hyperoncotic albumin solution decreases sodium reabsorption by the proximal tubule. The present micropuncture studies test the thesis that albumin infusion depresses proximal reabsorption by an effect unrelated to expansion of the plasma volume, perhaps due to an effect of parathyroid hormone (PTH) on proximal sodium reabsorption. Infusion of salt-poor hyperoncotic albumin significantly decreased plasma ionized calcium, increased immunoreactive PTH (iPTH) in plasma, decreased sodium reabsorption by the proximal tubule, and increased phosphate clearance. In contrast, infusions of albumin, in which the ionized calcium was restored to normal plasma levels, had no significant effect on ionized calcium, iPTH, proximal reabsorption, or phosphate clearance in intact dogs. Similarly, in parathyroidectomized animals given a constant replacement infusion of PTH, albumin infusion had no significant effect on proximal reabsorption or phosphate clearance. Plasma volume was markedly expanded following albumin infusion in all groups of dogs. These findings (a) indicate that PTH plays a significant role in the decrease in sodium reabsorption by the renal proximal tubule after salt-poor hyperoncotic albumin infusion, and (b) dissociate preferential expansion of the plasma volume from decreases in sodium reabsorption by the proximal tubule. PMID:11344563

Knox, F G; Schneider, E G; Willis, L R; Strandhoy, J W; Ott, C E; Cuche, J L; Goldsmith, R S; Arnaud, C D

1974-02-01

195

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

NASA Technical Reports Server (NTRS)

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

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

2000-01-01

196

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

NASA Technical Reports Server (NTRS)

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

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

1997-01-01

197

Distinctive Tooth-Extraction Socket Healing: Bisphosphonate Versus Parathyroid Hormone Therapy  

PubMed Central

Background Patients with osteoporosis who receive tooth extractions are typically on either oral bisphosphonate or parathyroid hormone (PTH) therapy. Currently, the consequence of these therapies on hard- and soft-tissue healing in the oral cavity is not clearly defined. The aim of this study is to determine the differences in the therapeutic effect on tooth-extraction wound healing between bisphosphonate and PTH therapies. Methods Maxillary second molars were extracted in Sprague Dawley rats (n = 30), and either bisphosphonate (zoledronate [Zol]), PTH, or saline (vehicle control [VC]) was administered for 10 days (n = 10 per group). Hard-tissue healing was evaluated by microcomputed tomography and histomorphometric analyses. Collagen, blood vessels, inflammatory cell infiltration, and cathepsin K expression were assessed in soft tissue using immunohistochemistry, quantitative polymerase chain reaction, and immunoblotting. Results Both therapies significantly increased bone fill and suppressed vertical bone loss. However, considerably more devital bone was observed in the sockets of rats on Zol versus VC. Although Zol increased the numbers of blood vessels, the total blood vessel area in soft tissue was significantly smaller than in VC. PTH therapy increased osteoblastic bone formation and suppressed osteoclasts. PTH therapy promoted soft-tissue maturation by suppressing inflammation and stimulating collagen deposition. Conclusion Zoledronate therapy deters whereas PTH therapy promotes hard- and soft-tissue healing in the oral cavity, and both therapies prevent vertical bone loss. PMID:23688101

Kuroshima, Shinichiro; Mecano, Rodan B.; Tanoue, Ryuichiro; Koi, Kiyono; Yamashita, Junro

2014-01-01

198

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

PubMed

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

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

2014-04-01

199

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

PubMed

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

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

2012-11-01

200

Parathyroid hormone-like peptide in normal and neoplastic human endocrine tissues.  

PubMed

PTH-like peptide (PLP) is produced by tumors commonly associated with hypercalcemia as well as nonneoplastic tissues and several endocrine glands and tumors. To characterize the distribution of PLP in human endocrine tissues and tumors, we localized PLP in formalin-fixed paraffin-embedded material using the avidin-biotin-peroxidase technique with polyclonal antisera. Among peptide hormone-producing tissues, PLP was identified in nontumorous adenohypophysis and pituitary adenomas; medullary thyroid carcinomas; normal, hyperplastic, and adenomatous parathyroids; adrenal medulla and pheochromocytomas; normal pancreatic islets; and endocrine tumors of pancreas, gut, and lung, including small cell carcinomas. In other endocrine tissues PLP was identified in nontumorous thyroid follicular epithelium, colloid nodules, and follicular neoplasms; normal adrenal cortex, adrenocortical adenomas, and carcinomas; nontumorous testicular Leydig cells; normal ovarian granulosa and thecal cells; an ovarian thecoma and a granulosa cell tumor; placental trophoblast; and decidua. These results demonstrate that PLP is localized in many normal and neoplastic endocrine cells, including those not known to influence extracellular calcium homeostasis. The presence of PLP in a variety of endocrine tissues suggests that it may play a local physiological role in the growth or function of endocrine cells. PMID:2229275

Asa, S L; Henderson, J; Goltzman, D; Drucker, D J

1990-11-01

201

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

PubMed Central

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

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

2014-01-01

202

Parathyroid hormone-related protein activates Wnt signaling to specify the embryonic mammary mesenchyme  

PubMed Central

Parathyroid hormone-related protein (PTHrP) regulates cell fate and specifies the mammary mesenchyme during embryonic development. Loss of PTHrP or its receptor (Pthr1) abolishes the expression of mammary mesenchyme markers and allows mammary bud cells to revert to an epidermal fate. By contrast, overexpression of PTHrP in basal keratinocytes induces inappropriate differentiation of the ventral epidermis into nipple-like skin and is accompanied by ectopic expression of Lef1, ?-catenin and other markers of the mammary mesenchyme. In this study, we document that PTHrP modulates Wnt/?-catenin signaling in the mammary mesenchyme using a Wnt signaling reporter, TOPGAL-C. Reporter expression is completely abolished by loss of PTHrP signaling and ectopic reporter activity is induced by overexpression of PTHrP. We also demonstrate that loss of Lef1, a key component of the Wnt pathway, attenuates the PTHrP-induced abnormal differentiation of the ventral skin. To characterize further the contribution of canonical Wnt signaling to embryonic mammary development, we deleted ?-catenin specifically in the mammary mesenchyme. Loss of mesenchymal ?-catenin abolished expression of the TOPGAL-C reporter and resulted in mammary buds with reduced expression of mammary mesenchyme markers and impaired sexual dimorphism. It also prevented the ectopic, ventral expression of mammary mesenchyme markers caused by overexpression of PTHrP in basal keratinocytes. Therefore, we conclude that a mesenchymal, canonical Wnt pathway mediates the PTHrP-dependent specification of the mammary mesenchyme. PMID:23034629

Hiremath, Minoti; Dann, Pamela; Fischer, Jennifer; Butterworth, Daniela; Boras-Granic, Kata; Hens, Julie; Van Houten, Joshua; Shi, Wei; Wysolmerski, John

2012-01-01

203

Carbonic anhydrase activity of chick osteoclasts is increased by parathyroid hormone  

SciTech Connect

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

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

1987-12-01

204

Expression of parathyroid hormone-related protein confers malignant potential to mucoepidermoid carcinoma.  

PubMed

Parathyroid hormone-related protein (PTHrP) is known to induce bone resorption by activating RANKL as well as PTH. PTHrP plays a central role in humoral hypercalcemia, and its expression has been reported to be closely associated with bone metastasis of breast carcinoma. PTHrP expression in oral squamous carcinoma cell lines was investigated, and PTHrP was expressed in oral squamous cell carcinoma cell lines similar to that in a prostate carcinoma cell line. Mucoepidermoid carcinoma is the most common malignant salivary gland tumor composed of different types of cells including a squamous component. Its clinical behavior is highly variable and ranges from slow-growing and indolent to locally aggressive and highly metastatic. We examined the PTHrP expression in mucoepidermoid carcinoma and assessed the significance of its correlation with clinicopathological features. Immunohistochemical detection of PTHrP was carried out in 21 cases of mucoepidermoid carcinoma in the head and neck region. PTHrP was highly detectable in intermediate and epidermoid cells, and abundant expression of PTHrP in intermediate cells had a significant association with cancer malignancy, including lymph node metastasis and/or tumor recurrence. These results suggest that PTHrP expression can be used as a prognostic factor for mucoepidermoid carcinoma. PMID:23588777

Nagamine, Kyosuke; Kitamura, Tetsuya; Yanagawa-Matsuda, Aya; Ohiro, Yoichi; Tei, Kanchu; Hida, Kyoko; Higashino, Fumihiro; Totsuka, Yasunori; Shindoh, Masanobu

2013-06-01

205

Critical role of activating transcription factor 4 in the anabolic actions of parathyroid hormone in bone.  

PubMed

Parathyroid hormone (PTH) is a potent anabolic agent for the treatment of osteoporosis. However, its mechanism of action in osteoblast and bone is not well understood. In this study, we show that the anabolic actions of PTH in bone are severely impaired in both growing and adult ovariectomized mice lacking bone-related activating transcription factor 4 (ATF4). Our study demonstrates that ATF4 deficiency suppresses PTH-stimulated osteoblast proliferation and survival and abolishes PTH-induced osteoblast differentiation, which, together, compromise the anabolic response. We further demonstrate that the PTH-dependent increase in osteoblast differentiation is correlated with ATF4-dependent up-regulation of Osterix. This regulation involves interactions of ATF4 with a specific enhancer sequence in the Osterix promoter. Furthermore, actions of PTH on Osterix require this same element and are associated with increased binding of ATF4 to chromatin. Taken together these experiments establish a fundamental role for ATF4 in the anabolic actions of PTH on the skeleton. PMID:19851510

Yu, Shibing; Franceschi, Renny T; Luo, Min; Fan, Jie; Jiang, Di; Cao, Huiling; Kwon, Tae-Geon; Lai, Yumei; Zhang, Jian; Patrene, Kenneth; Hankenson, Kurt; Roodman, G David; Xiao, Guozhi

2009-01-01

206

International Union of Basic and Clinical Pharmacology. XCIII. The Parathyroid Hormone Receptors-Family B G Protein-Coupled Receptors.  

PubMed

The type-1 parathyroid hormone receptor (PTHR1) is a family B G protein-coupled receptor (GPCR) that mediates the actions of two polypeptide ligands; parathyroid hormone (PTH), an endocrine hormone that regulates the levels of calcium and inorganic phosphate in the blood by acting on bone and kidney, and PTH-related protein (PTHrP), a paracrine-factor that regulates cell differentiation and proliferation programs in developing bone and other tissues. The type-2 parathyroid hormone receptor (PTHR2) binds a peptide ligand, called tuberoinfundibular peptide-39 (TIP39), and while the biologic role of the PTHR2/TIP39 system is not as defined as that of the PTHR1, it likely plays a role in the central nervous system as well as in spermatogenesis. Mechanisms of action at these receptors have been explored through a variety of pharmacological and biochemical approaches, and the data obtained support a basic "two-site" mode of ligand binding now thought to be used by each of the family B peptide hormone GPCRs. Recent crystallographic studies on the family B GPCRs are providing new insights that help to further refine the specifics of the overall receptor architecture and modes of ligand docking. One intriguing pharmacological finding for the PTHR1 is that it can form surprisingly stable complexes with certain PTH/PTHrP ligand analogs and thereby mediate markedly prolonged cell signaling responses that persist even when the bulk of the complexes are found in internalized vesicles. The PTHR1 thus appears to be able to activate the G?s/cAMP pathway not only from the plasma membrane but also from the endosomal domain. The cumulative findings could have an impact on efforts to develop new drug therapies for the PTH receptors. PMID:25713287

Gardella, Thomas J; Vilardaga, Jean-Pierre

2015-04-01

207

Vitamin D and DBP: the free hormone hypothesis revisited.  

PubMed

The last five years have witnessed a remarkable renaissance in vitamin D research and a complete re-evaluation of its benefits to human health. Two key factors have catalyzed these changes. First, it now seems likely that localized, tissue-specific, conversion of 25-hydroxyvitamin D (25OHD) to 1,25-dihydroxyvitamin D (1,25(OH)2D) drives many of the newly recognized effects of vitamin D on human health. The second key factor concerns the ongoing discussion as to what constitutes adequate or optimal serum vitamin D (25OHD) status, with the possibility that vitamin D-deficiency is common to communities across the globe. These two concepts appear to be directly linked when low serum concentrations of 25OHD compromise intracrine generation of 1,25(OH)2D within target tissues. But, is this an over-simplification? Pro-hormone 25OHD is a lipophilic molecule that is transported in the circulation bound primarily to vitamin D binding protein (DBP). While the association between 25OHD and DBP is pivotal for renal handling of 25OHD and endocrine synthesis of 1,25(OH)2D, what is the role of DBP for extra-renal synthesis of 1,25(OH)2D? We hypothesize that binding to DBP impairs delivery of 25OHD to the vitamin D-activating enzyme 1?-hydroxylase in some target cells. Specifically, it is unbound, 'free' 25OHD that drives many of the non-classical actions of vitamin D. Levels of 'free' 25OHD are dependent on the concentration of DBP and alternative serum binding proteins such as albumin, but will also be influenced by variations in DBP binding affinity for specific vitamin D metabolites. The aim of this review will be to discuss the merits of 'free 25OHD' as an alternative marker of vitamin D status, particularly in the context of non-classical responses to vitamin D. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. PMID:24095930

Chun, Rene F; Peercy, Bradford E; Orwoll, Eric S; Nielson, Carrie M; Adams, John S; Hewison, Martin

2014-10-01

208

Effects of antidiuretic hormone, parathyroid hormone and glucagon on transepithelial voltage and resistance of the cortical and medullary thick ascending limb of Henle's loop of the mouse nephron  

Microsoft Academic Search

The effect of antidiuretic hormone (arginine vasopressin, AVP, 10?10mol.l?1), parathyroid hormone (PTH, 10?8 mol.l?8) and glucagon (10?8 mol.l?1) on the transepithelial potential difference (PDte) and the transepithelial resistance (Rte) were tested in in vitro perfused cortical (cTAL) and medullary (mTAL) thick ascending limbs of Henle's loop of the mouse\\u000a nephron. When compared with mTAL segments (PDte: 8.5±0.4 mV,n=16), cTAL segments

M. Wittner; A. Di Stefano

1990-01-01

209

Vitamin D analogs: Therapeutic applications and mechanisms for selectivity  

Microsoft Academic Search

The vitamin D endocrine system plays a central role in mineral ion homeostasis through the actions of the vitamin D hormone, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], on the intestine, bone, parathyroid gland, and kidney. The main function of 1,25(OH)2D3 is to promote the dietary absorption of calcium and phosphate, but effects on bone, kidney and the parathyroids fine-tune the mineral levels. In

Alex J. Brown; Eduardo Slatopolsky

2008-01-01

210

The Necessity and Reliability of Intraoperative Parathyroid Hormone (PTH) Testing in Patients with Mild Hyperparathyroidism and PTH Levels in the Normal Range  

Microsoft Academic Search

Background  Intraoperative parathyroid hormone (IoPTH) testing is useful in the management of hyperparathyroidism. The successful removal\\u000a of hypersecreting parathyroids is indicated by a decrease in PTH levels >50% within 15 min. A subset of patients with mild\\u000a hyperparathyroidism will actually have starting PTH levels in the normal range. We sought to determine if IoPTH testing is\\u000a necessary in these patients and if

Amal AlhefdhiScott; Scott N. Pinchot; Ruth Davis; Rebecca S. Sippel; Herbert Chen

211

Parathyroid hormone-dependent signaling pathways regulating genes in bone cells  

NASA Technical Reports Server (NTRS)

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.

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

2002-01-01

212

Effect of Zoledronate on the Responses of Osteocytes to Acute Parathyroid Hormone  

PubMed Central

The bone anabolic effect of parathyroid hormone (PTH) therapy is blunted when used in patients who were previously on bisphosphonate treatment. Osteocytes may play a role in the bisphosphonate silencing effect on PTH therapy since bisphosphonates have been shown to reach the lacuno-canalicular system. In vivo osteocyte studies pose a significant challenge. For the current study, we developed a simple method to isolate RNA from the cortical bone enriched with osteocytes. Our purpose was to investigate how zoledronate (ZA) treatment modulates the responses of osteocytes and the bone marrow (BM) to an acute PTH treatment. Mice received ZA treatment for 3 months and a single PTH injection prior to euthanasia. Bone was histomorphometrically evaluated. Gene expression was assessed at the RNA level in osteocytes and BM. Endothelial progenitor cells (EPCs) and ??T-cells were analyzed in the BM and blood using flow cytometry. We found that ZA treatment altered bone responses to PTH. The expression of sfrp4, a Wnt antagonist, was significantly increased in ZA-affected osteocytes. BM EPCs were increased in response to acute PTH but not when treatment was combined with ZA. ZA treatment augmented EPCs in the BM but not in blood which suggests that ZA treatment may have differential effects between the BM and blood. These findings indicate that osteocytes and BM EPCs in mice on ZA treatment respond differently to acute PTH from those not receiving ZA. This may partially explain the mechanisms of previous reports that ZA therapy attenuates the anabolic effect of PTH in bone. PMID:23503790

Kuroshima, Shinichiro; Elliott, Kirk William; Yamashita, Junro

2013-01-01

213

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

PubMed Central

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

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

1975-01-01

214

Conjugation of cell-penetrating peptides to parathyroid hormone affects its structure, potency, and transepithelial permeation.  

PubMed

Delivery of therapeutic peptides and proteins by the use of cell-penetrating peptides (CPPs) as carriers has been suggested as a feasible strategy. The aim of the present study was to investigate the effect of conjugating a series of well-known CPPs to the biologically active part of parathyroid hormone, i.e., PTH(1-34), and to evaluate the effect with regard to secondary structure, potency in Saos-2 cells, immunogenicity, safety, as well as the transepithelial permeation across monolayers by using the Caco-2 cell culture model. Further, co-administration of CPP and PTH(1-34) as an alternative to covalent conjugation was compared with regard to the transepithelial permeation. CPP-conjugated PTH(1-34) fusion peptides were successfully expressed in Escherichia coli and purified from inclusion bodies. No clear correlation between the degree of secondary structure of the CPP-conjugated PTH(1-34) fusion peptides and their potency was found, albeit a general decrease in permeation was observed for both N- and C-terminally CPP-conjugated PTH(1-34) as compared to native PTH(1-34). However, attachment of CPP to the N-terminus significantly increased permeation across Caco-2 cell monolayers as compared to the corresponding C-terminally CPP-conjugated PTH(1-34). In addition, the nonaarginine sequence proved to be the only CPP capable of increasing permeation when conjugated to PTH(1-34) as compared to co-administration of CPP and PTH(1-34). This enhancement effect was, however, associated with an unacceptably low level of cell viability. In conclusion, covalent conjugation of CPPs to PTH(1-34) influenced the secondary structure, potency, and transepithelial permeation efficiency of the resulting conjugate, and hence this approach appears not to be favorable as compared to co-administration when optimizing CPP-mediated permeation of PTH(1-34) across an intestinal epithelium. PMID:25611217

Kristensen, Mie; de Groot, Anne Marit; Berthelsen, Jens; Franzyk, Henrik; Sijts, Alice; Nielsen, Hanne Mørck

2015-03-18

215

Variability of Parathyroid Hormone and Other Markers of Bone Mineral Metabolism in Patients Receiving Hemodialysis  

PubMed Central

Background and objectives: Clinical management of mineral bone disorder in patients with kidney failure is guided by biochemical targets, in particular parathyroid hormone (PTH) concentration. The biologic variation of PTH and other bone mineral markers was measured in hemodialysis patients to better define their role in management. Design, setting, participants, & measurements: Intact PTH, biointact (whole-molecule) PTH, calcium, albumin-adjusted calcium, phosphate, and alkaline phosphatase (ALP) were measured in nonfasting samples obtained twice a week (both short-dialysis interval) over a 6-week period in 22 stable hemodialysis patients. Concurrently, samples were obtained from 12 healthy volunteers. Intraindividual coefficients of variance (CVI) were calculated and used to derive the reference change value (RCV) required to be 95% certain that a change has occurred. Results: CVI of all markers was significantly (P < 0.05) greater in patients than in healthy volunteers. For phosphate, ALP, and PTH this implies that an increased number of samples is required to estimate an individual's homeostatic set point. CVI of intact PTH was 25.6% in hemodialysis patients and 19.2% in healthy volunteers. A greater RCV should be used for patients (72%) compared with healthy volunteers (54%). Ideally 26 specimens should be measured to estimate a patient's intact PTH homeostatic set point (within ±10%) with 95% probability. The CVI of biointact PTH was at least as high as that for intact PTH. Conclusions: The uncertainty of PTH estimation in an individual significantly undermines its value as a tool in the management of chronic kidney disease-mineral bone disorder using current management approaches. PMID:20498246

Gardham, Clare; Stevens, Paul E.; Delaney, Michael P.; LeRoux, Marica; Coleman, Adrian

2010-01-01

216

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

SciTech Connect

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

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

2005-07-01

217

Parathyroid hormone reverses radiation induced hypovascularity in a murine model of distraction osteogenesis  

PubMed Central

Background Radiation treatment results in a severe diminution of osseous vascularity. Intermittent parathyroid hormone (PTH) has been shown to have an anabolic effect on osteogenesis, though its impact on angiogenesis remains unknown. In this murine model of distraction osteogenesis, we hypothesize that radiation treatment will result in a diminution of vascularity in the distracted regenerate and that delivery of intermittent systemic PTH will promote angiogenesis and reverse radiation induced hypovascularity. Materials and methods Nineteen Lewis rats were divided into three groups. All groups underwent distraction of the left mandible. Two groups received radiation treatment to the left mandible prior to distraction, and one of these groups was treated with intermittent subcutaneous PTH (60 ?g/kg, once daily) beginning on the first day of distraction for a total duration of 21 days. One group underwent mandibular distraction alone, without radiation. After consolidation, the rats were perfused and imaged with micro-CT angiography and quantitative vascular analysis was performed. Results Radiation treatment resulted in a severe diminution of osseous vascularity in the distracted regenerate. In irradiated mandibles undergoing distraction osteogenesis, treatment with intermittent PTH resulted in significant increases in vessel volume fraction, vessel thickness, vessel number, degree of anisotropy, and a significant decrease in vessel separation (p < 0.05). No significant difference in quantitative vascularity existed between the group that was irradiated, distracted and treated with PTH and the group that underwent distraction osteogenesis without radiation treatment. Conclusions We quantitatively demonstrate that radiation treatment results in a significant depletion of osseous vascularity, and that intermittent administration of PTH reverses radiation induced hypovascularity in the murine mandible undergoing distraction osteogenesis. While the precise mechanism of PTH-induced angiogenesis remains to be elucidated, this report adds a key component to the pleotropic effect of intermittent PTH on bone formation and further supports the potential use of PTH to enhance osseous regeneration in the irradiated mandible. PMID:23643680

Kang, Stephen Y.; Deshpande, Sagar S.; Donneys, Alexis; Rodriguez, Joey J.; Nelson, Noah S.; Felice, Peter A.; Chepeha, Douglas B.; Buchman, Steven R.

2013-01-01

218

Parathyroid hormone-related protein is a gravisensor in lung and bone cell biology  

NASA Astrophysics Data System (ADS)

Parathyroid Hormone-related Protein (PTHrP) has been shown to be essential for the development and homeostatic regulation of lung and bone. Since both lung and bone structure and function are affected by microgravity, we hypothesized that 0 × g down-regulates PTHrP signaling. To test this hypothesis, we suspended lung and bone cells in the simulated microgravity environment of a Rotating Wall Vessel Bioreactor, which simulates microgravity, for up to 72 hours. During the first 8 hours of exposure to simulated 0 × g, PTHrP expression fell precipitously, decreasing by 80-90%; during the subsequent 64 hours, PTHrP expression remained at this newly established level of expression. PTHrP production decreased from 12 pg/ml/hour to 1 pg/ml/hour in culture medium from microgravity-exposed cells. The cells were then recultured at unit gravity for 24hours, and PTHrP expression and production returned to normal levels. Based on these findings, we have obtained bones from rats flown in space for 2 weeks (Mission STS-58, SL-2). Analysis of PTHrP expression by femurs and tibias from these animals (n=5) revealed that PTHrP expression was 60% lower than in bones from control ground-based rats. Interestingly, there were no differences in PTHrP expression by parietal bone from space-exposed versus ground-based animals, indicating that the effect of weightlessness on PTHrP expression is due to the unweighting of weight-bearing bones. This finding is consistent with other studies of microgravity-induced osteoporosis. The loss of the PTHrP signaling mechanism may be corrected using chemical agents that up-regulate this pathway. In conclusion, PTHrP represents a stretch-sensitive paracrine signaling mechanism that may sense gravity.

Torday, J. S.

2003-10-01

219

Comparison of Hypotensive Response following Intravenous Injection of Parathyroid Hormone 1-84 and 1-34 in Conscious Rats  

Microsoft Academic Search

Activation of parathyroid hormone 1 (PTH-1) receptors on vascular smooth muscle cells causes relaxation and decreases blood\\u000a pressure in rats and humans. However, when PTH(1-84) and PTH(1-34) were injected in anesthetized rats, PTH(1-34) produced\\u000a a greater decrease in blood pressure. This study quantified the dose-response relationship of the hypotensive response to\\u000a intravenously injected PTH(1-84) and PTH(1-34) in conscious rats and

K. R. Scott; J. Fox

2006-01-01

220

Development of Parathyroid Hormone and Calcitonin-Activated Adenylate Cyclases in Embryonic Chicken Limb and in Cultured Cells from Embryonic Chicken Limb  

Microsoft Academic Search

Activation of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] by parathyroid hormone (PTH) and calcitonin was measured as a function of stage of development in embryonic chicken limb buds. Responsiveness to both hormones develops in the tissue at the time when nascent bone is forming. In addition, a temporal sequence of development of hormone response was observed, with a PTH-activated

James E. Zull; Steven Krug; Diane Abel; Arnold I. Caplan

1978-01-01

221

Effect of Vitamin D Nutrition on Parathyroid Adenoma Weight: Pathogenetic and Clinical Implications  

Microsoft Academic Search

In primary hyperparathyroidism, adenoma size is a major deter- minant of disease severity and manner of presentation, but the reason for the large variation in size (.100-fold) is unknown. One factor could be the level of vitamin D nutrition, because in India, where vitamin D deficiency is endemic, adenomas are larger and the disease more severe than in the U.S.

D. SUDHAKER RAO; M. HONASOGE; GEORGE W. DIVINE; EVELYN R. PHILLIPS; MIN W. LEE; MOHAMMED R. ANSARI; GARY B. TALPOS; A. MICHAEL PARFITT

2000-01-01

222

Intermittent Fugu parathyroid hormone 1 (1–34) is an anabolic bone agent in young male rats and osteopenic ovariectomized rats  

Microsoft Academic Search

Human parathyroid hormone (hPTH) is currently the only treatment for osteoporosis that forms new bone. Previously we described a fish equivalent, Fugu parathyroid hormone 1 (fPth1) which has hPTH-like biological activity in vitro despite fPth1(1–34) sharing only 53% identity with hPTH(1–34). Here we demonstrate the in vivo actions of fPth1(1–34) on bone. In study 1, young male rats were injected

Julie F. McManus; Rachel A. Davey; Helen E. MacLean; Elizabeth A. Doust; W. S. Maria Chiu; Natalie A. Sims; Mary L. Bouxsein; Vaida Glatt; Jeffrey D. Zajac; Janine A. Danks

2008-01-01

223

Cloning of a parathyroid hormone/parathyroid hormone-related peptide receptor (PTHR) cDNA from a rat osteosarcoma (UMR 106) cell line: Chromosomal assignment of the gene in the human, mouse, and rat genomes  

SciTech Connect

Complementary DNAs spanning the entire coding region of the rat parathyroid hormone/parathyroid hormone-related peptide receptor (PTHR) were isolated from a rat osteosarcoma (UMR 106) cell-line cDNA library. The longest of these clones (rPTHrec4) was used to chromosomally assign the PTHR gene in the human, rat, and mouse genomes. By somatic cell hybrid analysis, the gene was localized to human chromosome 3 and rat chromosome 8; by in situ hybridization, the gene was mapped to human chromosome 3p21.1-p22 and to mouse chromosome 9 band F; and by interspecific backcross analysis, the Pthr gene segregated with the transferrin (Trf) gene in chromosome 9 band F. Mouse chromosome 9 and rat chromosome 8 are known to be highly homologous and to also show synteny conservation with human chromosome 3. These three chromosomes share the transferrin gene (TF), the myosin light polypeptide 3 gene (MYL3), and the acelpeptide hydrolase gene (APEH). These results add a fourth gene, the PTHR gene, to the synteny group conserved in these chromosomes. 34 refs., 7 figs. 1 tab.

Pausova, Z.; Bourdon, J.; Clayton, D.; Janicic, N.; Goltzman, D.; Hendy, G.N. (McGill Univ. and Royal Victoria Hospital, Montreal Quebec (Canada)); Mattei, M.G. (INSERM, Marseille (France)); Seldin, M.F. (Duke Univ. Medical Center, Durham, NC (United States)); Riviere, M.; Szpirer, J. (Universite Libre de Bruxelles, Rhode-St-Genese (Belgium)) (and others)

1994-03-01

224

Vitamin D receptor activation and survival in chronic kidney disease  

Microsoft Academic Search

Replacement of activated vitamin D has been the cornerstone of therapy for secondary hyperparathyroidism (SHPT). Recent findings from several large observational studies have suggested that the benefits of vitamin D receptor activators (VDRA) may extend beyond the traditional parathyroid hormone (PTH)-lowering effect, and could result in direct cardiovascular and metabolic benefits. The advent of several new analogs of the activated

C P Kovesdy; K Kalantar-Zadeh

2008-01-01

225

Conformational studies of RS-66271, an analog of parathyroid hormone-related protein with pronounced bone anabolic activity.  

PubMed

Both the parathyroid hormone (PTH) and the functionally similar parathyroid hormone-related protein (PTHrP) have served as templates for the development of novel bone anabolic agents for the treatment of osteoporosis. The PTHrP analog RS-66271 (Vickery, B. H.; Avnur, Z.; Cheng Y.; Chiou, S.-S.; Leaffer, D.; Caulfield, J. P.; Kimmel, D. B.; Ho, T.; Krstenansky, J. L. J. Bone Miner. Res. 1996, 11, 1943-1951), in which the amino acids 22-31 have been substituted by the sequence E22-L-L-E-K-L-L-E-K-L31 (a model amphiphilic peptide), is a potent bone anabolic agent in vivo. Therefore, RS-66271 is a good candidate for structural analysis with the aim of developing a structure-activity relationship. The structural characterization described here was carried out in aqueous solution employing circular dichroism and nuclear magnetic resonance spectroscopy. We find that the incorporated amphiphilic decapeptide is indeed helical. In addition, it induces the adjacent residues, up to residue 16, to adopt the helical conformation. The helical domain, including residues 16-32, incorporates most of the previously identified principal receptor binding domain PTHrP(25-34). We discuss the relevance of the distinct and extensive helicity in light of the reduced in vitro receptor affinity/ activity and the enhanced in vivo bone anabolic efficacy of RS-66271. PMID:9301664

Pellegrini, M; Bisello, A; Rosenblatt, M; Chorev, M; Mierke, D F

1997-09-12

226

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

SciTech Connect

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

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

2013-02-01

227

Recombinant human parathyroid hormone (PTH 1-34) and low-intensity pulsed ultrasound have contrasting additive effects during fracture healing  

Microsoft Academic Search

Fracture healing is thought to be naturally optimized; however, recent evidence indicates that it may be manipulated to occur at a faster rate. This has implications for the duration of morbidity associated with bone injuries. Two interventions found to accelerate fracture healing processes are recombinant human parathyroid hormone [1-34] (PTH) and low-intensity pulsed ultrasound (LIPUS). This study aimed to investigate

Stuart J. Warden; David E. Komatsu; Johanna Rydberg; Julie L. Bond; Sean M. Hassett

2009-01-01

228

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...

229

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

Microsoft Academic Search

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

Adriana S Dusso; Masanori Tokumoto

2011-01-01

230

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

PubMed

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

Kakuta, Takatoshi; Sawada, Kaichiro

2014-12-01

231

About the Parathyroid Glands  

MedlinePLUS

... the kidneys, increasing your chances of having a kidney stone. In fact, everyone with a fracture that isn’ ... of major trauma and everyone who has a kidney stone should have blood calcium and parathyroid hormone measured. ...

232

Chicken Parathyroid Hormone Gene Expression in Response to Gastrin, Omeprazole, Ergocalciferol, and Restricted Food Intake  

Microsoft Academic Search

.   Treatment with omeprazole, a long-acting proton pump inhibitor of acid secretion, induces hypergastrinemia. In chickens,\\u000a omeprazole induces growth not only of the acid-producing mucosa (probably reflecting the trophic action of gastrin), but also\\u000a of the parathyroid glands (hypertrophy + hyperplasia), while suppressing bone density and body weight gain without affecting\\u000a blood calcium. The first part of the present study

R. Gagnemo-Persson; A. Samuelsson; R. Håkanson; P. Persson

1997-01-01

233

Cutting edge: Parathyroid hormone facilitates macrophage efferocytosis in bone marrow via proresolving mediators resolvin D1 and resolvin D2.  

PubMed

Bone marrow macrophages stimulate skeletal wound repair and osteoblastic bone formation by poorly defined mechanisms. Specialized proresolving mediators of inflammation drive macrophage efferocytosis (phagocytosis of apoptotic cells) and resolution, but little is known regarding this process in the bone marrow. In this study, metabololipidomic profiling via liquid chromatography mass spectrometry revealed higher levels of specialized proresolving mediators in the bone marrow relative to the spleen. The endocrine and bone anabolic agent parathyroid hormone increased specialized proresolving mediator levels, including resolvins (Rvs), in bone marrow. Human and murine primary macrophages efferocytosed apoptotic osteoblasts in vitro, and RvD1 and RvD2 (10 pM-10 nM) enhanced this process. These findings support a unique profile of specialized lipid mediators in bone marrow that contribute to a feedback system for resolution of inflammation and maintenance of skeletal homeostasis. PMID:24890726

McCauley, Laurie K; Dalli, Jesmond; Koh, Amy J; Chiang, Nan; Serhan, Charles N

2014-07-01

234

Small molecule inhibition of the Na(+)/H(+) exchange regulatory factor 1 and parathyroid hormone 1 receptor interaction.  

PubMed

We have identified a series of small molecules that bind to the canonical peptide binding groove of the PDZ1 domain of NHERF1 and effectively compete with the association of the C-terminus of the parathyroid hormone 1 receptor (PTH1R). Employing nuclear magnetic resonance and molecular modeling, we characterize the mode of binding that involves the GYGF loop important for the association of the C-terminus of PTH1R. We demonstrate that the common core of the small molecules binds to the PDZ1 domain of NHERF1 and displaces a (15)N-labeled peptide corresponding to the C-terminus of PTH1R. The small size (molecular weight of 192) of this core scaffold makes it an excellent candidate for further elaboration in the development of an inhibitor for this important protein-protein interaction. PMID:25171053

Fitzpatrick, Jeremy M; Pellegrini, Maria; Cushing, Patrick R; Mierke, Dale F

2014-09-23

235

[Parathyroid Hormone-related Peptide( PTHrP) Producing Lung Cancer Presenting Hypercalcemia;Report of a Case].  

PubMed

An 82-year-old man was admitted to our hospital with hemoptysis and weight loss. Chest computed tomography(CT) showed a 90 mm mass with cavity formation in the right lower lobe adjacent to chest wall. Laboratory data revealed hypercalcemia and elevation of parathyroid hormone-related protein C (PTHrP). He was diagnosed as squamous cell carcinoma of lung by transbronchial lung biopsy (TBLB) [cT3aN1M0]. Nausea and anorexia due to hypercalcemia became worse and a right middle and lower lobectomy was performed because of difficult control of symptoms by medicine and worsening of his general condition. His symptoms were improved immediately after surgery. PMID:25743561

Okagawa, Takehiko; Hiramatsu, Yoshinori

2015-03-01

236

Peptide mapping of recombinant human parathyroid hormone by enzymatic digestion and subsequent fast-atom bombardment mass spectrometry.  

PubMed

Peptide maps of recombinant human parathyroid hormone (rhPTH) were determined by both trypsin and V-8 protease digestion with subsequent fast-atom bombardment mass spectrometry (FAB-MS). Coverage of the sequence was 85% when using trypsin and 90% when using V-8 protease. Five rhPTH variants that were recombinantly produced as models of Asn deamidated type degradation products were measured, and molecular weight differences between their respective deamidated peptide fragments were completely detected. In the V-8 protease digests of some variants, characteristic peptide ions caused by the deamidation were observed and this greatly facilitated the assignment and recognition of the deamidated position. Our data suggest that FAB-mapping of rhPTH via the protease digestion methods used, appears to have great potential for structural investigations of the peptide. PMID:7756699

Nabuchi, Y; Kuboniwa, H; Takasu, H; Asoh, Y; Ushio, H

1995-01-01

237

Treatment for chemotherapy-induced alopecia in mice using parathyroid hormone agonists and antagonists linked to a collagen binding domain.  

PubMed

Parathyroid hormone (PTH) agonists and antagonists have been shown to improve hair growth after chemotherapy; however, rapid clearance and systemic side-effects complicate their usage. To facilitate delivery and retention to skin, we fused PTH agonists and antagonists to the collagen binding domain (CBD) of Clostridium histolyticum collagenase. in-vitro studies showed that the agonist fusion protein, PTH-CBD, bound collagen and activated the PTH/parathyroid hormone-related peptide receptor in SaOS-2 cells. The antagonist fusion proteins, PTH(7-33)-CBD and PTH([-1]-33)-CBD, also bound collagen and antagonized PTH(1-34) effect in SaOS-2 cells; however, PTH(7-33)-CBD had lower intrinsic activity. Distribution studies confirmed uptake of PTH-CBD to the skin at 1 and 12 hr after subcutaneous injection. We assessed in vivo efficacy of PTH-CBD and PTH(7-33)-CBD in C57BL/6J mice. Animals were depilated to synchronize the hair follicles; treated on Day 7 with agonist, antagonist, or vehicle; treated on Day 9 with cyclophosphamide (150 mg/kg i.p.) or vehicle; and sacrificed on Day 39. Normal mice (no chemo and no treatment) showed rapid regrowth of hair and normal histology. Chemo+Vehicle mice showed reduced hair regrowth and decreased pigmentation; histology revealed reduced number and dystrophic anagen/catagen follicles. Chemo+Antagonist mice were grossly and histologically indistinguishable from Chemo+Vehicle mice. Chemo+Agonist mice showed more rapid regrowth and repigmentation of hair; histologically, there was a normal number of hair follicles, most of which were in the anagen phase. Overall, the agonist PTH-CBD had prominent effects in reducing chemotherapy-induced damage of hair follicles and may show promise as a therapy for chemotherapy-induced alopecia. PMID:22130912

Katikaneni, Ranjitha; Ponnapakkam, Tulasi; Suda, Hirofumi; Miyata, Shigeru; Sakon, Joshua; Matsushita, Osamu; Gensure, Robert C

2012-09-01

238

Abundant expression of parathyroid hormone-related protein in primary rat aortic smooth muscle cells accompanies serum-induced proliferation.  

PubMed Central

Parathyroid hormone-related protein (PTHrP), which is responsible for producing hypercalcemia in patients with humoral hypercalcemia of malignancy, has recently been identified in several normal tissues. Because PTHrP, like parathyroid hormone (PTH), is known to exhibit vasodilatory properties, we investigated the expression and regulation of PTHrP mRNA in cultured rat aortic smooth muscle cells (SMC). We report here that PTHrP mRNA is expressed in SMC and is markedly induced by serum in a time- and concentration-dependent fashion. Addition of 10% fetal calf serum to serum-deprived, confluent cells, resulted in a marked induction of PTHrP mRNA by 2 h with a peak at 4-6 h. PTHrP was detected in SMC by immunocytochemistry and radioimmunoassay of conditioned medium, and was shown to be up-regulated within 24 h after the addition of serum. The serum induction of PTHrP mRNA was blocked by actinomycin D and by cycloheximide indicating the need for protein synthesis to evoke the serum effect on PTHrP gene transcription. In addition, treatment with dexamethasone, which has been previously shown to reduce the constitutive expression of PTHrP in human cancer cells, also blunted the serum induction of PTHrP mRNA in SMC. Treatment of quiescent cells with the serum mitogens platelet-derived growth factor or insulin-like growth factor-I had no effect on PTHrP, whereas the vasoactive peptides endothelin, norepinephrine and thrombin stimulated PTHrP expression. Exogenous addition of recombinant PTHrP-(1-141) had no significant effect on SMC DNA synthesis as measured by [3H]thymidine incorporation. In summary, the abundance of PTHrP mRNA and the characteristics of its regulation in SMC suggest a major role for PTHrP as a local modulator in vascular smooth muscle. Images PMID:1752945

Hongo, T; Kupfer, J; Enomoto, H; Sharifi, B; Giannella-Neto, D; Forrester, J S; Singer, F R; Goltzman, D; Hendy, G N; Pirola, C

1991-01-01

239

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

PubMed

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

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

2012-04-01

240

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

PubMed

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

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

2012-11-01

241

Regulation of hormone secretion and cytosolic Ca2+ by extracellular Ca2+ in parathyroid cells and C-cells: role of voltage-sensitive Ca2+ channels.  

PubMed

The two dihydropyridine enantiomers, (+)202-791 and (-)202-791, that act as voltage-sensitive Ca2+ channel agonist and antagonist, respectively, were examined for effects on cytosolic Ca2+ concentrations ([Ca2+]i) and on hormones secretion in dispersed bovine parathyroid cells and a rat medullary thyroid carcinoma (rMTC) cell line. In both cell types, small increases in the concentration of extracellular Ca2+ evoked transient followed by sustained increases in [Ca2+]i, as measured with fura-2. Increases in [Ca2+]i obtained by raised extracellular Ca2+ were associated with a stimulation of secretion of calcitonin (CT) and calcitonin gene-related peptide (CGRP) in rMTC cells, but an inhibition of secretion of parathyroid hormone (PTH) in parathyroid cells. The Ca2+ channel agonist (+)202-791 stimulated whereas the antagonist (-)202-791 inhibited both transient and sustained increases in [Ca2+]i induced by extracellular Ca2+ in rMTC cells. Secretion of CT and CGRP was correspondingly enhanced and depressed by (+)202-791 and (-)202-791, respectively. In contrast, neither the agonist nor the antagonist affected [Ca2+]i and PTH secretion in parathyroid cells. Depolarizing concentrations of extracellular K+ increased [Ca2+]i and hormone secretion in rMTC cells and both these responses were potentiated or inhibited by the Ca2+ channel agonist or antagonist, respectively. The results suggest a major role of voltage-sensitive Ca2+ influx in the regulation of cytosolic Ca2+ and hormones secretion in rMTC cells. Parathyroid cells, on the other hand, appear to lack voltage-sensitive Ca2+ influx pathways and regulate PTH secretion by some alternative mechanism. PMID:2458067

Muff, R; Nemeth, E F; Haller-Brem, S; Fischer, J A

1988-08-15

242

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

PubMed Central

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

2014-01-01

243

Minimally Invasive Radioguided Parathyroid (MIRP) Surgery  

MedlinePLUS Videos and Cool Tools

... to localize the tumor using a probe—and assessment of individual parathyroid gland hormone production in real ... a parathyroid patient? Is there a significantly higher risk for a patient in their 80s versus patients ...

244

Fibroblast Growth Factor-23 and Parathyroid Hormone Are Associated with Post-Transplant Bone Mineral Density Loss  

PubMed Central

Background and objectives: Among the multiple factors contributing to bone mineral density (BMD) loss after renal transplantation, hypophosphatemia is increasingly recognized to play an important role. Hypophosphatemia occurs in up to 90% of the renal transplant recipients in the early post-transplant period and is caused by renal phosphate wasting. We hypothesized that a high pretransplant level of the recently described phosphaturic hormone fibroblast growth factor 23 (FGF-23) is a risk factor for accelerated BMD loss occurring within the first post-transplant year. Design, setting, participants, & measurements: We performed a two-center observational retrospective cohort study in 127 incident renal transplant recipients. Serum full-length FGF-23, parathyroid hormone (PTH), and parameters of mineral metabolism were determined at the time of transplantation. BMD was assessed by osteodensitometry at the time of transplantation and 1 year later. Results: A moderate decrease of BMD was observed during the first post-transplant year. High FGF-23 levels were associated with BMD loss at the lumbar spine and total hip region, whereas low PTH levels were associated with BMD loss at all three regions. Cumulative doses of prednisone and post-transplant serum phosphate level were not correlated with BMD changes. Conclusion: Our data indicate that patients with a high serum FGF-23 level and/or a low PTH level at the time of transplantation are at risk for increased BMD loss during the first post-transplant year. PMID:20634326

Claes, Kathleen; Devogelaer, Jean-Pierre; Vanderschueren, Dirk; Depresseux, Genevieve; Goffin, Eric; Evenepoel, Pieter

2010-01-01

245

Mandibular Bone Formation Rates in Aged Ovariectomized Rats Treated with Anti-resorptive Agents Alone and in Combination with Intermittent Parathyroid Hormone  

Microsoft Academic Search

Anti-resorptive agents-including estrogen (E), calcitonin (CT), and bisphosphonates-are established in the treatment of osteoporosis. Intermittent administration of parathyroid hormone (PTH) stimulates bone formation and is a possible therapeutic agent for the restoration of bone mass. The purpose was to determine the effects of the anti-resorptive agents alone and in combination with intermittent PTH on bone formation in the mandible and

J. Hunziker; TJ Wronski; S. C. Miller

2000-01-01

246

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

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

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

2001-01-01

247

Identification of a cDNA Encoding a Parathyroid Hormone-Like Peptide from a Human Tumor Associated with Humoral Hypercalcemia of Malignancy  

Microsoft Academic Search

Humoral hypercalcemia of malignancy is a common paraneoplastic syndrome that appears to be mediated in many instances by a parathyroid hormone-like peptide. Poly(A)+ RNA from a human renal carcinoma associated with this syndrome was enriched by preparative electrophoresis and used to construct an enriched cDNA library in phage lambda gt10. The library was screened with a codon-preference oligonucleotide synthesized on

Marguerite Mangin; Andrew C. Webb; Barbara E. Dreyer; James T. Posillico; Kyoji Ikeda; Eleanor C. Weir; Andrew F. Stewart; Neil H. Bander; Leonard Milstone; David E. Barton; Uta Francke; Arthur E. Broadus

1988-01-01

248

Intermittent administration of human parathyroid hormone enhances bone formation and union at the site of cancellous bone osteotomy in normal and ovariectomized rats  

Microsoft Academic Search

Intermittent administration of human parathyroid hormone (hPTH) has an anabolic effect on bone in animals and humans and is expected to be a potent agent for the treatment of osteoporosis. However, little is known about the effects of hPTH on cancellous bone healing after cancellous bone fractures or osteotomies. We evaluated whether hPTH enhanced bone union at the site of

Koji Nozaka; Naohisa Miyakoshi; Yuji Kasukawa; Shigeto Maekawa; Hideaki Noguchi; Yoichi Shimada

2008-01-01

249

Effects of parathyroid hormone and calcitonin on Na + , Cl ? , K + , Mg 2+ and Ca 2+ transport in cortical and medullary thick ascending limbs of mouse kidney  

Microsoft Academic Search

The effect of parathyroid hormone (PTH) on transepithelial Na+, Cl-, K+, Ca2+ and Mg2+ transport was investigated in isolated perfused cortical thick ascending limbs (cTAL) and that of human calcitonin (hCT) was tested in both cortical and medullary thick ascending limbs (mTAL) of the mouse nephron. The transepithelial ion net fluxes (Jx) were determined by electron probe analysis of the

A. Di Stefano; M. Wittner; R. Nitschke; R. Braitsch; R. Greger; C. Bailly; C. Amiel; N. Roinel; C. Rouffignac

1990-01-01

250

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

Microsoft Academic Search

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

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

1989-01-01

251

Influence of a low calcium and phosphorus diet on the anabolic effect of human parathyroid hormone (1-38) in female rats  

Microsoft Academic Search

Parathyroid hormone (PTH) or synthetic N-terminal PTH fragments administered intermittently have been established as anabolic agents in animal and human bones. In the present study, the influence of a low calcium diet on the anabolic effect of human PTH(1-38) [hPTH(1-38)] was investigated. Forty-eight 10-week-old female Sprague-Dawley rats were randomly assigned to a diet with a low calcium content (LCa) or

P. D Steiner; R Forrer; M Kneissel; J. A Gasser; J. S Thomsen; Li Mosekilde; J.-L Riond

2001-01-01

252

Vitamin D and the Immune System from the Nephrologist's Viewpoint.  

PubMed

Vitamin D and its analogues are widely used as treatments by clinical nephrologists, especially when treating chronic kidney disease (CKD) patients with secondary hyperparathyroidism. As CKD progresses, the ability to compensate for elevations in parathyroid hormone (PTH) and fibroblast growth factor-23 and for decreases in 1,25(OH)2D3 becomes inadequate, which results in hyperphosphatemia, abnormal bone disorders, and extra-skeletal calcification. In addition to its calciotropic effect on the regulation of calcium, phosphate, and parathyroid hormone, vitamin D has many other noncalciotropic effects, including controlling cell differentiation/proliferation and having immunomodulatory effects. There are several immune dysregulations that can be noted when renal function declines. Physicians need to know well both the classical and nonclassical functions of vitamin D. This review is an analysis from the nephrologist's viewpoint and focuses on the relationship between the vitamin D and the immune system, together with vitamin's clinical use to treat kidney diseases. PMID:24587915

Lang, Cheng-Lin; Wang, Min-Hui; Chiang, Chih-Kang; Lu, Kuo-Cheng

2014-01-01

253

Vitamin D and the Immune System from the Nephrologist's Viewpoint  

PubMed Central

Vitamin D and its analogues are widely used as treatments by clinical nephrologists, especially when treating chronic kidney disease (CKD) patients with secondary hyperparathyroidism. As CKD progresses, the ability to compensate for elevations in parathyroid hormone (PTH) and fibroblast growth factor-23 and for decreases in 1,25(OH)2D3 becomes inadequate, which results in hyperphosphatemia, abnormal bone disorders, and extra-skeletal calcification. In addition to its calciotropic effect on the regulation of calcium, phosphate, and parathyroid hormone, vitamin D has many other noncalciotropic effects, including controlling cell differentiation/proliferation and having immunomodulatory effects. There are several immune dysregulations that can be noted when renal function declines. Physicians need to know well both the classical and nonclassical functions of vitamin D. This review is an analysis from the nephrologist's viewpoint and focuses on the relationship between the vitamin D and the immune system, together with vitamin's clinical use to treat kidney diseases. PMID:24587915

Wang, Min-Hui; Chiang, Chih-Kang; Lu, Kuo-Cheng

2014-01-01

254

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

PubMed Central

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

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

2012-01-01

255

Interrelationship between serum concentrations of 1,25-dihydroxyvitamin D, parathyroid hormone and renal haemodynamics after low dose cyclosporin.  

PubMed

It is unclear whether cyclosporin A (CsA) alters the synthesis of 1,25-dihydroxyvitamin D3 [1,25(OH)2D] by the normal human kidney. Serial changes in 1,25(OH)2D, parathyroid hormone (PTH), GFR and renal blood flow were compared in 14 patients with psoriasis who were being treated with less than 5 mg/kg/day of cyclosporin for 3 months. GFR fell significantly although there were no significant changes in serum 1,25(OH)2D, 25-hydroxyvitamin D or PTH. Absolute values for GFR and PTH were negatively correlated (rP = -0.54; p < 0.001) as were the changes in GFR and PTH observed during CsA therapy (rP = -0.73; p < 0.05). The significant fall in serum magnesium was not significantly correlated with changes in PTH. The close relationship between changes in GFR and PTH suggests that a reduction of GFR within the normal range is enough to stimulate production of PTH. CsA does not appear to stimulate the synthesis of 1,25(OH)2D3 in man. PMID:7700211

Edwards, B D; Davies, M; Mawer, E B; Chalmers, R J; Testa, H J; Ballardie, F W

1994-01-01

256

Regulation of human organic anion transporter 4 by parathyroid hormone-related protein and protein kinase A  

PubMed Central

Human organic anion transporter 4 (hOAT4) belongs to a family of organic anion transporters that play critical roles in the body disposition of clinically important drugs, including anti-human immunodeficiency virus therapeutics, anti-tumor drugs, antibiotics, antihypertensives, and anti-inflammatories. hOAT4 is abundantly expressed in the kidney and placenta. In the current study, we examined the regulation of hOAT4 by parathyroid hormone-related protein (PTHrP) and protein kinase A (PKA) in kidney COS-7 cells. PTHrP induced a time- and concentration-dependent stimulation of hOAT4 transport activity. The stimulation of hOAT4 activity by PTHrP mainly resulted from an increased cell surface expression without a change in total cell expression of the transporter. Activation of PKA by Bt2-cAMP also resulted in a stimulation of hOAT4 activity through an increased cell surface expression of the transporter. However, PTHrP-induced stimulation of hOAT4 activity could not be prevented by treating hOAT4-expressing cells with the PKA inhibitor H89. We concluded that both PTHrP and activation of PKA stimulate hOAT4 activity through redistribution of the transporter from intracellular compartments to the cell surface. However, PTHrP regulates hOAT4 activity by mechanisms independent of PKA pathway. PMID:23097748

Duan, Peng; Li, Shanshan; You, Guofeng

2012-01-01

257

Pharmacokinetics in rats of a long-acting human parathyroid hormone-collagen binding domain peptide construct.  

PubMed

The pharmacokinetics of a hybrid peptide consisting of the N-terminal biologically active region of human parathyroid hormone (PTH) linked to a collagen-binding domain (CBD) were evaluated in female Sprague-Dawley rats. The peptide, PTH-CBD, consists of the first 33 amino acids of PTH linked as an extension of the amino acid chain to the CBD peptide derived from ColH collagenase of Clostridium histolyticum. Serum concentrations arising from single dose administration by the subcutaneous and intravenous routes were compared with those measured following route-specific mole equivalent doses of PTH(1-34). Population-based modeling demonstrated similar systemic absorption kinetics and bioavailability for both peptides. Exposure to PTH-CBD was sixfold higher because of a systemic clearance of approximately 20% relative to PTH(1-34); however, these kinetics were consistent with more than 95% of a dose being eliminated from serum within 24 h. Results obtained support continued investigation of PTH-CBD as a bone-targeted anabolic agent for the treatment of postmenopausal osteoporosis. PMID:24399637

Stratford, Robert; Vu, Christopher; Sakon, Joshua; Katikaneni, Ranjitha; Gensure, Robert; Ponnapakkam, Tulasi

2014-02-01

258

Effects of selective oxidation of 1-34 bovine parathyroid hormone on its renal actions in the rabbit.  

PubMed

Oxidation of both of the methionine residues (positions 8 and 18) in parathyroid hormone (PTH) eliminates many of its biological effects. The present studies were performed to examine the actions of 1,34 bovine PTH and 1-34 bovine PTH oxidized selectively at Met 8, at Met 18, and at both sites on renal electrolyte handling and on adenylate cyclase (AC) stimulation. In clearance studies in anesthetized rabbits, PTH caused a phosphaturia and an anticalciuria. PTH also stimulated renal proximal tubular AC in vitro and increased renal cortical cAMP content in vivo. PTH oxidized at Met 18 was anticalciuric, but not phosphaturic, stimulated renal AC and increased cortical cAMP content. PTH oxidized at Met 8 also produced an anticalciuria without a phosphaturia, but only weakly stimulated AC and did not alter cortical cAMP content. PTH oxidized at both Met 8 and Met 18 was phosphaturic but not anticalciuric, was a weak agonist for AC and decreased cortical cAMP content. In the isolated perfused rabbit proximal straight tubule, PTH inhibited fluid and phosphate transport, whereas the doubly oxidized peptide was inactive. The data are consistent with the possibility that the effects of PTH on renal tubular phosphorus transport are mediated by more than one mechanism and are, in part, independent of the cAMP messenger system. PMID:2554103

Pitts, T O; Puschett, J B; Rose, M E; Zull, J E

1989-01-01

259

Cryopreserved cord blood progenitors and their cell adhesion molecules are increased by coculture with osteoblasts and parathyroid hormone.  

PubMed

Despite advantages of cord blood (CB) cells, such as their high capacity for proliferation and low immunogenicity, CB transplantation is also associated with delayed neutrophil and platelet recovery relative to bone marrow transplantation. These limitations arise from the reduced abundances of primitive hematopoietic stem cells expressing adhesion molecules in CB relative to bone marrow. To address this limitation, we evaluated whether human parathyroid hormone (hPTH) could increase the number of primitive hematopoietic stem cells with adhesion molecules in cryopreserved CB. When cryopreserved CB cells were cocultured with differentiated osteoblasts in the presence of hPTH, numbers of CD34CD38 cells increased 4-fold after 7 days. Exposure to hPTH promoted clonogenic cell expansion and significantly increased the expression of adhesion molecules, such as CD44 (a cell surface glycoprotein) and VLA-4 (?4 integrin) in CD34 cells. This result shows that short-term coculture of cryopreserved CB with differentiated osteoblasts in the presence of hPTH may improve the rate of engraftment of CD34 cells through increasing the abundances of primitive cells bearing adhesion molecules. PMID:23426002

Jang, Yun Kyung; Kim, Miyeon; Jin, Hye Jin; Choi, Soo Jin; Oh, Wonil; Lee, Young-Ho

2013-08-01

260

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

PubMed Central

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

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

2012-01-01

261

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

PubMed Central

Aims The relationship between parathyroid hormone (PTH) and the cardiorenal metabolic syndrome was examined among non-diabetic persons with chronic kidney disease (CKD). Methods In a cross-sectional analysis, the relationship between PTH levels and the cardiorenal metabolic syndrome was investigated in 3,215 non-diabetic participants in the National Kidney Foundation-Kidney Early Evaluation Program (KEEP 2.0) found to have CKD (eGFR <60 ml/min/1.73 m2). Results In unadjusted analyses, the prevalence of the cardiorenal metabolic syndrome increased along increasing PTH quartiles (31.7, 33.8, 37.3, and 48.7%, respectively, p for trend <0.0001). After multivariate adjustment, as compared to the first PTH quartile, odds of the cardiorenal metabolic syndrome were 16% (p = 0.18), 35% (p = 0.006), and 80% (p < 0.0001) higher for the second, third, and fourth quartiles, respectively. When taken as a continuous predictor, each standard deviation increase of natural log transformed PTH was associated with 26% (p < 0.0001) higher odds of the cardiorenal metabolic syndrome. The association of PTH with the cardiorenal metabolic syndrome was not modified by age or gender (p for interaction was not significant for both modifiers). Conclusions Among an outpatient non-diabetic population with CKD, higher PTH levels were associated with a higher prevalence of the cardiorenal metabolic syndrome. PMID:22258399

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

2011-01-01

262

Therapy for alopecia areata in mice using parathyroid hormone agonists and antagonists, linked to a collagen-binding domain.  

PubMed

Alopecia areata is a common form of hair loss in which autoimmune-mediated destruction of hair follicles causes patchy hair loss, for which there is no adequate therapy. Parathyroid hormone (PTH) induces the hair cycle and promotes hair growth. PTH-CBD is a fusion protein of PTH and a bacterial collagen-binding domain (CBD), leading to targeted delivery to and retention in the skin collagen. We tested the effects of a single dose of PTH-CBD (low or high dose) on an animal model for alopecia areata, the C3H/HeJ engrafted mouse. In all the treated animals, there was a rapid (1-4 days) increase in hair growth, with sustained effects observed over a 2-month period (7/10 total treated mice<40% hair loss based on gray scale analysis, vs. 2/5 in vehicle control animals). Histological examination revealed massive stimulation of anagen VI hair follicles in treated animals despite an ongoing immune response. PTH-CBD thus shows promise as a therapy for alopecia areata, likely in conjunction with a mild immune suppressant, such as hydrocortisone cream. PMID:24326563

Katikaneni, Ranjitha; Gulati, Rohan; Suh, Daniel; Sakon, Joshua; Seymour, Andrew; Ponnapakkam, Tulasi; Gensure, Robert

2013-12-01

263

Parathyroid hormone (1-34) modulates odontoblast proliferation and apoptosis via PKA and PKC-dependent pathways.  

PubMed

Parathyroid hormone (PTH) plays a key role in the development and homeostasis of mineralized tissues such as bone and dentine. We have reported that PTH (1-34) administration can increase dentine formation in mice and that this hormone modulates in vitro mineralization of odontoblast-like cells. The purpose of the present study was to investigate whether PTH (1-34) participates in the proliferative and apoptotic signaling of odontoblast-like cells (MDPC23). MDPC23 cells were exposed to 50 ng/ml hPTH (1-34) or vehicle for 1 (P1), 24 (P24), or 48 (P48) hours, and the cell proliferation, apoptosis, and cell number were evaluated. To examine whether changes in the proliferative and apoptotic signaling in response to PTH involve protein kinases A (PKA) and/or C (PKC), MDPC23 cells were exposed to PTH with or without PKC or PKA signaling pathway inhibitors. Overall, the results showed that the PKA pathway acts in response to PTH exposure maintaining levels of cell proliferation, while the PKC pathway is mainly involved for longer exposure to PTH (24 or 48 h), leading to the reduction of cell proliferation and increase of apoptosis. The exposure to PTH reduced the cell number in relation to the control group in a time-dependent manner. In conclusion, PTH modulates odontoblast-like cell proliferative and apoptotic response in a time-dependent manner. Both PKC and PKA pathways participate in PTH-induced modulation in an antagonist mode. PMID:25012507

Guimarães, Gustavo Narvaes; Rodrigues, Thaisângela Lopes; de Souza, Ana Paula; Line, Sergio Roberto; Marques, Marcelo Rocha

2014-09-01

264

Intermittently administered parathyroid hormone 1-34 reverses bone loss and structural impairment in orchiectomized adult rats.  

PubMed

Male osteoporosis is emerging as a central theme in bone research. As in females, hypogonadism appears as a principal risk factor in men that leads to bone loss and increased fracture incidence. Intermittently administered parathyroid hormone (PTH) reverses bone loss in sex hormone-deprived women and female animals and increases bone mass in elderly men and normal male animals. This study was carried out to assess whether the PTH anabolic activity is also effective in adult castrated males and to gain insight into the underlying tissue processes. Bilateral orchiectomy (ORX) or sham-ORX was performed in 13-week old rats. Five weeks later, the ORX rats were treated intermittently with human PTH(1-34), 80 microg/kg/day or vehicle for 6 weeks. Femora were evaluated by quantitative micro-computed tomography followed by dynamic histomorphometry. The trabecular bone volume density showed 40% and 56% ORX-induced loss in the distal metaphysis at 6 weeks and 12 weeks post-ORX, respectively. PTH(1-34) induced supraphysiologic recovery of this bone loss (155% recovery) consequent to a vast increase in trabecular thickness (174% over sham-ORX controls) and a partial reversal (62%) of the decrease in trabecular number. As compared with the results in 12-week, orchiectomized vehicle-administered rats, the PTH(1-34) treatment induced a significant decrease in osteoclast number (20%) and twofold increase in bone formation rate. While ORX did not affect the femoral diaphysis, PTH(1-34) induced marked cortical thickening via the stimulation of endosteal mineral appositional rate (154% over ORX rats). These data portray PTH(1-34) as a highly potent bone anabolic agent in adult ORX rats, mainly by increasing both the trabecular and cortical thicknesses through its effect on osteoblasts and osteoclasts. The adult ORX rat is useful for investigating the processes involved in bone anabolic activity in castrated osteoporotic males and for the development of bone anabolic agents for treating this condition. PMID:15812598

Gabet, Yankel; Kohavi, David; Müller, Ralph; Chorev, Michael; Bab, Itai

2005-11-01

265

The Parathyroid  

Microsoft Academic Search

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

H. Rubén Harach

266

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

PubMed Central

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

Karaca, Halit

2014-01-01

267

Synovium as a source of increased amino-terminal parathyroid hormone-related protein expression in rheumatoid arthritis. A possible role for locally produced parathyroid hormone-related protein in the pathogenesis of rheumatoid arthritis.  

PubMed Central

Proinflammatory cytokines, including tumor necrosis factor (TNF) and interleukin 1 (IL-1), mediate the joint destruction that characterizes rheumatoid arthritis (RA). Previous studies have shown that parathyroid hormone-related protein (PTHrP) is a member of the cascade of proinflammatory cytokines induced in parenchymal organs during lethal endotoxemia. To test the hypothesis that NH2-terminal PTHrP, a potent bone resorbing agent, could also be a member of the synovial cascade of tissue-destructive cytokines whose expression is induced in RA, PTHrP expression was examined in synovium and synoviocytes obtained from patients with RA and osteoarthritis (OA). PTHrP production, as determined by measurement of immunoreactive PTHrP(1-86) in tissue explant supernatants, was increased 10-fold in RA versus OA synovial tissue. Synovial lining cells and fibroblast-like cells within the pannus expressed both PTHrP and the PTH/PTHrP receptor, findings that were confirmed by in vitro studies of cultured synoviocytes. TNF-alpha and IL-1beta stimulated PTHrP expression in synoviocytes, while dexamethasone and interferon-gamma, agents with some therapeutic efficacy in the treatment of RA, inhibited PTHrP release. Treatment of synoviocytes with PTHrP(1-34) stimulated IL-6 secretion. These results suggest that proinflammatory cytokine-stimulated production of NH2-terminal PTHrP by synovial tissue directly invading cartilage and bone in RA may mediate joint destruction through direct effects on cartilage or bone, or, indirectly, via the induction of mediators of bone resorption in the tumor-like synovium. PMID:9525978

Funk, J L; Cordaro, L A; Wei, H; Benjamin, J B; Yocum, D E

1998-01-01

268

Effects of antidiuretic hormone, parathyroid hormone and glucagon on transepithelial voltage and resistance of the cortical and medullary thick ascending limb of Henle's loop of the mouse nephron.  

PubMed

The effect of antidiuretic hormone (arginine vasopressin, AVP, 10(-10) mol.l-1), parathyroid hormone (PTH, 10(-8) mol.l-1) and glucagon (10(-8) mol.l-1) on the transepithelial potential difference (PDte) and the transepithelial resistance (Rte) were tested in in vitro perfused cortical (cTAL) and medullary (mTAL) thick ascending limbs of Henle's loop of the mouse nephron. When compared with mTAL segments (PDte: 8.5 +/- 0.4 mV, n = 16), cTAL segments displayed a high PDte of 15.7 +/- 0.9 mV (n = 11) at the beginning of perfusion experiments which reached a value of 9.4 +/- 0.6 mV (n = 11) after 38 +/- 4 min perfusion. Simultaneously Rte increased significantly from 24 +/- 3 to 28 +/- 1 omega cm2 (n = 11). When PTH, AVP or glucagon were added to the bath solution, PDte increased with PTH from 10.3 +/- 0.8 to 15.2 +/- 0.8 mV (n = 13), with AVP from 10.2 +/- 0.5 to 15.0 +/- 0.7 mV (n = 24) and with glucagon from 11.3 +/- 1.9 to 15.3 +/- 2.1 mV (n = 8). At the same time Rte decreased from 30 +/- 3 to 23 +/- 2 omega cm2, from 28 +/- 1 to 23 +/- 1 omega cm2 and from 23 +/- 2 to 18 +/- 2 omega cm2, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2336347

Wittner, M; Di Stefano, A

1990-03-01

269

Association of 25-hydroxy-vitamin D levels with semen and hormonal parameters  

PubMed Central

Vitamin D levels have been linked to various health outcomes including reproductive disorders. The purpose of this study was to explore the association between serum vitamin D level (25-hydroxy-vitamin D, or 25OHD) and semen and hormonal parameters. This is a cross-sectional study that included 170 healthy men recruited for the study of spermatogenesis from the general population. Men completed general and reproductive health questionnaires, and donated blood and semen samples. The main measures were hormonal (total and free testosterone, sex hormone-binding globulin, estradiol, follicle-stimulating hormone and luteinizing hormone) and semen parameters, adjusted (n=147) for age, body mass index (BMI), season, alcohol intake and smoking, in relation to categories of vitamin D levels, determined a priori. The mean age of the study population was 29.0±8.5 years and mean BMI was 24.3±3.2 kg m?2. The mean 25OHD was 34.1±15.06 ng ml?1. BMI showed a negative association with 25OHD. Sperm concentration, sperm progressive motility, sperm morphology, and total progressively motile sperm count were lower in men with ‘25OHD?50 ng ml?1' when compared to men with ‘20 ng ml?1?25OHD<50 ng ml?1'. Total sperm count and total progressive motile sperm count were lower in men with ‘25OHD<20 ng ml?1' when compared to men with ‘20 ng ml?1?25OHD<50 ng ml?1'. The adjusted means of various hormonal parameters did not show statistical difference in the different categories of 25OHD. In conclusion, serum vitamin D levels at high and low levels can be negatively associated with semen parameters. PMID:23042450

Hammoud, Ahmad O; Wayne Meikle, A; Matthew Peterson, C; Stanford, Joseph; Gibson, Mark; Carrell, Douglas T

2012-01-01

270

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

NASA Technical Reports Server (NTRS)

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

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

1999-01-01

271

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

PubMed Central

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

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

2011-01-01

272

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

SciTech Connect

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.

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

1991-01-01

273

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

PubMed

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

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

2014-01-01

274

Parathyroid hormone-related protein is induced by hypoxia and promotes expression of the differentiated phenotype of human articular chondrocytes.  

PubMed

PTHrP (parathyroid hormone-related protein) is crucial for normal cartilage development and long bone growth and acts to delay chondrocyte hypertrophy and terminal differentiation in the growth plate. After growth plate closure adult HACs (human articular chondrocytes) still produce PTHrP, suggesting a possible role for this factor in the permanent articular cartilage. However, the expression regulation and function of PTHrP in the permanent articular cartilage is unknown. Human articular cartilage is an avascular tissue and functions in a hypoxic environment. The resident chondrocytes have adapted to hypoxia and use it to drive their tissue-specific functions. In the present study, we explored directly in normal articular chondrocytes isolated from a range of human donors the effect of hypoxia on PTHrP expression and whether PTHrP can regulate the expression of the permanent articular chondrocyte phenotype. We show that in HACs PTHrP is up-regulated by hypoxia in a HIF (hypoxia-inducible factor)-1? and HIF-2?-dependent manner. Using recombinant PTHrP, siRNA-mediated depletion of endogenous PTHrP and by blocking signalling through its receptor [PTHR1 (PTHrP receptor 1)], we show that hypoxia-induced PTHrP is a positive regulator of the key cartilage transcription factor SOX9 [SRY (sex determining region on the Y chromosome)-box 9], leading to increased COL2A1 (collagen type II, ?1) expression. Our findings thus identify PTHrP as a potential factor for cartilage repair therapies through its ability to promote the differentiated HAC phenotype. PMID:23662774

Pelosi, Michele; Lazzarano, Stefano; Thoms, Brendan L; Murphy, Chris L

2013-11-01

275

Acute lithium administration impairs the action of parathyroid hormone on rat renal calcium, magnesium and phosphate transport.  

PubMed

1. Chronic lithium (Li+) treatment commonly produces a state of hyperparathyroidism in humans and rat although the mechanism is unknown. 2. The present study evaluated the acute effect of Li+ on renal electrolyte transport, particularly Ca2+ and Mg2+ in thyroparathyroidectomized (TPTX) and intact rats. 3. The acute administration of Li+ significantly increased water, sodium, potassium and phosphate excretion in both TPTX and intact animals; however, Ca2+ and Mg2+ excretion was only increased in the intact group. Fractional excretion (FE) of Ca2+ and Mg2+ increased from 2.2 +/- 0.2 to 3.5 +/- 0.3% and 12 +/- 2 to 18 +/- 2%, respectively (P < 0.01). 4. In further experiments in TPTX rats, Li+ administration inhibited the usual reduction in urine Ca2+ and Mg2+ excretion following parathyroid hormone (PTH) administration and inhibited the phosphaturia. However, supramaximal concentrations of PTH overcame this inhibitory effect. For example, an FECa of 3.8 +/- 0.2% was reduced to 1.4 +/- 0.2% and 1.7 +/- 0.2% with maximal and supramaximal PTH concentrations, respectively, while in the presence of Li+ an FECa of 4.0 +/- 0.2 was decreased to 2.8 +/- 0.2 and then 1.9 +/- 0.3% with the same PTH concentrations. 5. The inhibitory effect of Li+ was reduced with a lower plasma Li+ concentration (0.7 +/- 0.2 vs 1.6-1.8 mmol/L). The FEMg results were comparable. 6. These results demonstrate that Li+ directly inhibits PTH-mediated renal reabsorption of Ca2+ and Mg2+ and also blunts PTH-mediated phosphaturia. Therefore, the hyperparathyroidism in humans following Li+ treatment may be a consequence of reduced renal Ca2+ reabsorption. PMID:9784918

Carney, S; Jackson, P

1998-10-01

276

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

NASA Technical Reports Server (NTRS)

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

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

2002-01-01

277

The Effect of Bovine Parathyroid Hormone Withdrawal on MC3T3-E1 Cell Proliferation and Phosphorus Metabolism  

PubMed Central

Hypocalcemia and hypophosphatemia are common complications after parathyroidectomy (PTX). Sudden removal of high circulating levels of parathyroid hormone (PTH) causes decreased osteoclastic resorption resulting in a decreased bone remodeling space. These phenomena are likely due to an increased influx of calcium and phosphorus into bone. However, there are currently no data to support this hypothesis. In this study, we found that PTX significantly reduced levels of PTH, calcium and phosphate. Compared with preoperative levels, after 1 year, postoperative PTH, calcium and phosphate levels were 295.6 ± 173.7 pg/mL (P < 0.05), 86.62 ± 15.98 mg/dL (P < 0.05) and 5.56 ± 2.03 mg/dL (P < 0.05), respectively. We investigated continuous bovine PTH administration as well as withdrawal of bovine PTH stimulation in the mouse osteoblast precursor cell line MC3T3-E1. MC3T3-E1 cells were cultured with continuous bovine PTH treatment for 20 days or with transient bovine PTH treatment for 10 days. High doses of continuous bovine PTH exposure strongly reduced cell proliferation, alkaline phosphatase activity and the number of mineralized calcium nodules. However, withdrawal of bovine PTH (100 ng/mL) significantly increased the number of mineralized calcium nodules and caused a rapid decline in calcium and phosphorus content of culture medium. In conclusion, continuous exposure to bovine PTH inhibited osteoblast differentiation and reduced the formation of mineralized nodules. However, this inhibition was removed and mineralized nodule formation resumed with withdrawal of bovine PTH. According to the results of our clinical examinations and in vitro experiments, we hypothesize that the sudden removal of high levels of PTH may cause an increased influx of calcium and phosphorus into bone after PTX. PMID:25775025

Li, Sijia; Cui, Tongxia; Li, Zhonghe; Zhang, Bin; Li, Zhuo; Wu, Jianxiong; Liang, Xinling; Lin, Zheng; Shi, Wei

2015-01-01

278

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

PubMed

Parathyroid hormone (PTH) is a potent anabolic agent for bone, but the mechanism(s) by which it works remains imperfectly understood. Previous studies have indicated that PTH stimulates insulin-like growth factor (IGF) I production, but it remains uncertain whether IGF-I mediates some or all of the skeletal actions of PTH. To address this question, we examined the skeletal response to PTH in IGF-I-deficient (knockout [k/o]) mice. These mice and their normal littermates (NLMs) were given daily injections of PTH (80 microg/kg) or vehicle for 2 weeks after which their tibias were examined for fat-free weight (FFW), bone mineral content, bone structure, and bone formation rate (BFR), and their femurs were assessed for mRNA levels of osteoblast differentiation markers. In wild-type mice, PTH increased FFW, periosteal BFR, and cortical thickness (C.Th) of the proximal tibia while reducing trabecular bone volume (BV); these responses were not seen in the k/o mice. The k/o mice had normal mRNA levels of the PTH receptor and increased mRNA levels of the IGF-I receptor but markedly reduced basal mRNA levels of the osteoblast markers. Surprisingly, these mRNAs in the k/o bones increased several-fold more in response to PTH than the mRNAs in the bones from their wild-type littermates. These results indicate that IGF-I is required for the anabolic actions of PTH on bone formation, but the defect lies distal to the initial response of the osteoblast to PTH. PMID:12211426

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

2002-09-01

279

Comparative Genomic Hybridization Analysis of Human Parathyroid Tumors  

Microsoft Academic Search

Primary hyperparathyroidism is characterized by hypercalcemia and elevated parathy- roid hormone levels. It can be caused by overactivity of one (adenoma or carcinoma) or more (hyperpla- sia or multiple adenoma) parathyroid glands. Parathyroid adenoma and hyperplasia are usually mono- or oligoclonal neoplasms. To establish whether parathyroid cancer has a genetic composition distinct from parathyroid adenoma, we analyzed 10 adenoma and

Sunita K. Agarwal; Evelin Schröck; Mary Beth Kester; Lee Burns; Clara S. Heffess; Thomas Ried; Stephen J. Marx

280

Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism.  

PubMed

Serotonin and vitamin D have been proposed to play a role in autism; however, no causal mechanism has been established. Here, we present evidence that vitamin D hormone (calcitriol) activates the transcription of the serotonin-synthesizing gene tryptophan hydroxylase 2 (TPH2) in the brain at a vitamin D response element (VDRE) and represses the transcription of TPH1 in tissues outside the blood-brain barrier at a distinct VDRE. The proposed mechanism explains 4 major characteristics associated with autism: the low concentrations of serotonin in the brain and its elevated concentrations in tissues outside the blood-brain barrier; the low concentrations of the vitamin D hormone precursor 25-hydroxyvitamin D [25(OH)D3]; the high male prevalence of autism; and the presence of maternal antibodies against fetal brain tissue. Two peptide hormones, oxytocin and vasopressin, are also associated with autism and genes encoding the oxytocin-neurophysin I preproprotein, the oxytocin receptor, and the arginine vasopressin receptor contain VDREs for activation. Supplementation with vitamin D and tryptophan is a practical and affordable solution to help prevent autism and possibly ameliorate some symptoms of the disorder. PMID:24558199

Patrick, Rhonda P; Ames, Bruce N

2014-06-01

281

Parathyroid Hormone-Related Protein (107-139) Decreases Alkaline Phosphatase in Osteoblastic Osteosarcoma Cells UMR 106 by a Protein Kinase C-Dependent Pathway  

Microsoft Academic Search

.   The C-terminal (107-111) region of parathyroid hormone-related protein (PTHrP) appears to inhibit osteoclastic bone resorption,\\u000a and to affect osteoblastic growth and differentiation. We tested the effect of human PTHrP (107-139) on alkaline phosphatase\\u000a (ALP) activity in osteoblastic osteosarcoma UMR 106 cells. We found that this C-terminal PTHrP peptide, between 10 nM and\\u000a 10 fM, inhibited ALP activity in these

A. Valín; F. de Miguel; A. García-Ocaña; P. Esbrit

1999-01-01

282

Nuclear localization of the type 1 parathyroid hormone/parathyroid hormone-related peptide receptor in MC3T3-E1 cells: association with serum-induced cell proliferation.  

PubMed

We have recently demonstrated that the receptor for parathyroid hormone (PTH) and PTH-related peptide (PTHrP), PTHR, can be localized to the nucleus of cells within the liver, kidney, uterus, gut, and ovary of the rat. We set out to determine the localization of the PTHR in cultured osteoblast-like cells. MC3T3-E1, ROS 17/2.8, UMR106, and SaOS-2 cells were cultured in alpha-modified eagle medium containing 15% fetal calf serum under standard conditions. Untreated cells were grown on glass coverslips to 75-95% confluence and fixed in 1% paraformaldehyde. For experiments designed to examine cells synchronized by serum starvation, cells were grown on glass coverslips, starved of serum for 46 h, and then fixed at 2-h intervals for a total of 26 h after the addition of serum to the medium. Parallel sets of cells were pulsed with [3H]thymidine to track the DNA duplication interval. The PTHR was localized by immunocytochemistry using a primary antibody raised against a portion of the N-terminal extracellular domain of the PTHR. The results presented herein indicate that the PTHR attains a nuclear localization in each cell line examined. In UMR106 cells, PTHR immunoreactivity was restricted to the nucleolus. After cell synchronization, MC3T3-E1 cells double approximately 24 h after the addition of serum. Immunocytochemistry for the PTHR in these cells showed that the receptor staining is initially diffuse for the first 6 h, then becomes more perinuclear in distribution by 12-16 h. Nuclear localization of the receptor is achieved approximately 16-20 h after the addition of serum and remains there throughout the mitotic phase. Intense staining of mitotic and postmitotic cells was observed. No change in cell proliferation kinetics was observed in MC3T3-E1 cells cultured in the presence of 25 nM PTH(1-34). These data suggest an important role for the PTHR in the nucleus of MC3T3-E1 cells at the time of DNA synthesis and mitosis. PMID:10709993

Watson, P H; Fraher, L J; Natale, B V; Kisiel, M; Hendy, G N; Hodsman, A B

2000-03-01

283

Vitamin D and the skin.  

PubMed

Vitamin D is a fat-soluble nutrient that humans obtain through the diet and by synthesis in the skin upon exposure to ultraviolet B. Vitamin D is then converted by the liver to 25-hydroxyvitamin D, its major circulating form. This form is the best indicator of vitamin D nutritional status and is easily measured. Under the influence of parathyroid hormone, the kidney then converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, the biologically active, hormonal form of the nutrient that is important in the metabolism of calcium and phosphorus and is critical in building and maintaining healthy bones. Many cell types outside of the skeletal system, including various cells in the skin, also express the vitamin D receptor. In addition, many cell types convert circulating 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D for local use. This metabolite has been shown to exert potent effects on cellular differentiation, cellular proliferation, and immune regulation. It is theorized that by these mechanisms vitamin D and its analogues are effective treatment options for psoriasis and other skin diseases. Insufficient vitamin D nutritional status has been associated with a host of other diseases, most notably cancer. There is evidence that supplementation with vitamin D reduces the overall incidence of cancer, although current evidence is insufficient to prove a causative effect. Sunscreen use blocks the ability of the skin to photosynthesize vitamin D, although the effect this has on the vitamin D status of the general population is unclear. PMID:21034990

Shahriari, Mona; Kerr, Philip E; Slade, Karren; Grant-Kels, Jane E

2010-01-01

284

Pathophysiology of parathyroid hyperplasia in chronic kidney disease: preclinical and clinical basis for parathyroid intervention  

Microsoft Academic Search

Secondary hyperparathyroidism is characterised by ex- cessive secretion of parathyroid hormone and parathy- roid hyperplasia, resulting in both skeletal and extraskele- tal consequences. Recent basic and clinical studies have brought considerable advances in our understanding of the pathophysiology of parathyroid hyperplasia and have also provided practical therapeutic approaches, especially with regard to indications for parathyroid intervention. In this context, it

Shunsuke Goto; Hirotaka Komaba; Masafumi Fukagawa

2008-01-01

285

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

PubMed Central

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

2011-01-01

286

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

NASA Technical Reports Server (NTRS)

The purpose of this study was to determine if human parathyroid hormone-(1-38) (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.

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

1995-01-01

287

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

NASA Technical Reports Server (NTRS)

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

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

1994-01-01

288

Enhanced individual trabecular repair and its mechanical implications in parathyroid hormone and alendronate treated rat tibial bone.  

PubMed

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

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

2015-01-01

289

The single dose pharmacokinetic profile of a novel oral human parathyroid hormone formulation in healthy postmenopausal women.  

PubMed

Parathyroid hormone (PTH), currently the only marketed anabolic treatment for osteoporosis, is available as the full-length hormone, human PTH1-84, or as the human PTH1-34 fragment (teriparatide). Both must be administered as a daily subcutaneous (sc) injection. A new oral formulation of human PTH1-34 (PTH134) is being developed as a more convenient option for patients. In this single-center, partially-blinded, incomplete cross-over study, the safety, tolerability, and exposure of oral PTH134 (teriparatide combined with 2 different quantities of the absorption enhancer 5-CNAC) were assessed in 32 healthy postmenopausal women. 16 subjects were randomized to receive 4 single doses out of 6 different treatments: placebo, teriparatide 20 ?g sc, or 1, 2.5, 5 or 10 mg of oral PTH134 formulated with 200 mg 5-CNAC. Subsequently, another 16 subjects were randomized to receive 4 out of 6 different treatments: placebo, teriparatide 20 ?g sc, or 2.5 or 5 mg of oral PTH134 formulated with either 100 or 200 mg 5-CNAC. Doses were given ?6 days apart. All doses of PTH134 were rapidly absorbed, and showed robust blood concentrations in a dose-dependent manner. Interestingly, PTH1-34 disappeared from blood faster after oral than after sc administration. Specifically, 2.5 and 5 mg PTH134 (containing 200 mg 5-CNAC) demonstrated Cmax and AUC0-last values closest to those of sc teriparatide 20 ?g (Forsteo®). Mean+/-SD hPTH134 Cmax values were, respectively, 74+/-59, 138+/-101, 717+/-496, and 1624+/-1579 pg/mL for 1, 2.5, 5, and 10 mg doses of this peptide administered with 200 mg 5-CNAC; while mean+/-SD AUC (0-last) values were, respectively, 30+/-40, 62+/-69, 320+/-269, and 627+/-633 h*pg/mL. The corresponding estimates for teriparatide 20 ?g sc were 149+/-35 for Cmax and 236+/-58 for AUC (0-last) Ionized calcium remained within normal limits in all treatment groups except for 3 isolated events. Nine subjects withdrew due to treatment-related AEs. Of those, seven were taking PTH134 2.5 or 5 mg: three withdrew for symptomatic hypotension (two of whom were in the 200 mg 5-CNAC group), three because of delayed vomiting (two from the 200 mg 5-CNAC group), one was proactively withdrawn by the investigator for symptomatic hypercalcemia (receiving 2.5 mg/100 mg 5-CNAC) at slightly supra-normal total calcium but normal ionized serum calcium levels. One subject receiving teriparatide and one receiving placebo withdrew for symptomatic hypotension. No serious AEs were reported. In conclusion, the study demonstrated potential therapeutically relevant PTH1-34 systemic exposure levels after oral administration of PTH1-34 formulated with the absorption enhancer 5-CNAC. Doses of 2.5 and 5 mg of oral PTH134 achieved exposure levels closest to those of teriparatide 20 ?g sc, with a comparable incidence of AEs in healthy postmenopausal women. PMID:22289659

Hämmerle, Sibylle P; Mindeholm, Linda; Launonen, Aino; Kiese, Beate; Loeffler, Rolf; Harfst, Evita; Azria, Moise; Arnold, Michel; John, Markus R

2012-04-01

290

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

E-print Network

, supplementation and therapy, vitamin D Curr Opin Clin Nutr Metab Care 10:12­19. � 2007 Lippincott Williams. 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

Kalueff, Allan V.

291

Serial evaluation of parathyroid size by ultrasonography is another useful marker for the long-term prognosis of calcitriol pulse therapy in chronic dialysis patients.  

PubMed

To clarify whether the changes of parathyroid size have any correlations with the long-term prognosis of calcitriol pulse therapy, we examined the time course of serum levels of parathyroid hormone (PTH) and size of parathyroid glands in 14 chronic dialysis patients during and after the oral calcitriol pulse therapy. In 5 patients without any detectable glands, secondary hyperparathyroidism was easily controlled by calcitriol pulse therapy and then by conventional oral active vitamin D therapy. In 2 patients with detectable gland(s) in whom size of all parathyroid glands as well as PTH hypersecretion regressed to normal by calcitriol pulse therapy, secondary hyperparathyroidism could then remain controlled at least for 12 months after switching to conventional oral active vitamin D therapy. In contrast, in 7 patients in whom size of all parathyroid glands did not regress to normal by calcitriol pulse therapy, secondary hyperparathyroidism relapsed after switching to the conventional therapy, even if PTH hypersecretion could be controlled temporarily. Our findings suggest that the time course of parathyroid hyperplasia detected by ultrasonography is an important determinant of the efficacy and the prognosis of calcitriol pulse therapy. Thus, the change of parathyroid gland size as well as PTH hypersecretion should be taken into account for the management of secondary hyperparathyroidism. PMID:7830860

Fukagawa, M; Kitaoka, M; Yi, H; Fukuda, N; Matsumoto, T; Ogata, E; Kurokawa, K

1994-01-01

292

Long-term vitamin D3 supplementation may have adverse effects on serum lipids during postmenopausal hormone replacement therapy  

Microsoft Academic Search

Objective: The positive short-term effects of postmenopausal hormone replacement therapy (HRT) on serum lipids are well known, but it has been suggested that they vanish with time. Cholecalciferol (vitamin D3) is widely used to prevent postmenopausal osteoporosis but the influence of vitamin D3 on serum lipids is poorly known. The long-term effects of HRT and vitamin D3 on the concentrations

Anna-Mari Heikkinen; Marjo T Tuppurainen; Leo Niskanen; Marja Komulainen; Ilkka Penttila; Seppo Saarikoski

1997-01-01

293

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

Microsoft Academic Search

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

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

1970-01-01

294

Undescended parathyroid adenoma.  

PubMed

Undescended parathyroid adenomas are rare, representing 0.08% of all parathyroid adenomas; however, they make up 7% of the underlying cause of failed cervical exploration in patients with persistent primary hyperparathyroidism. A 43-year-old woman with no significant medical or family history presented with fatigue and was diagnosed with primary hyperparathyroidism; however, preoperative imaging including sestamibi scan and ultrasound was unable to identify the hyperfunctioning gland. She underwent a neck exploration and hemithyroidectomy and partial parathyroidectomy with failure of resolution of her disease. Subsequent work up including a CT of the neck demonstrated a 1.9 cm mass adjacent to the left submandibular gland. This was removed with postoperative normalisation of the patient's serum calcium and parathyroid hormone levels. PMID:25737222

Kanack, Melissa D; Maawy, Ali A; Oh, Deborah K; Bouvet, Michael

2015-01-01

295

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

PubMed Central

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

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

2015-01-01

296

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

PubMed Central

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

DeLuca, Hector F

2014-01-01

297

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

SciTech Connect

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

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

2009-04-01

298

JTT-305, an orally active calcium-sensing receptor antagonist, stimulates transient parathyroid hormone release and bone formation in ovariectomized rats.  

PubMed

Intermittent administration of parathyroid hormone (PTH) has a potent anabolic effect on bone in humans and animals. Calcium-sensing receptor (CaSR) antagonists stimulate endogenous PTH secretion through CaSR on the surface of parathyroid cells and thereby may be anabolic agents for osteoporosis. JTT-305 is a potent oral short-acting CaSR antagonist and transiently stimulates endogenous PTH secretion. The objective of the present study was to investigate the effects of JTT-305 on PTH secretion and bone in ovariectomized rats. Female rats, immediately after ovariectomy (OVX), were orally administered vehicle or JTT-305 (0.3, 1, or 3 mg/kg) for 12 weeks. The serum PTH concentrations were transiently elevated with increasing doses of JTT-305. In the proximal tibia, JTT-305 prevented OVX-induced decreases in both the cancellous and total bone mineral density (BMD) except for the 0.3mg/kg dose. At the 3mg/kg dose, JTT-305 increased the mineralizing surface and bone formation rate in histomorphometry. The efficacy of JTT-305 at the 3mg/kg dose on the BMD corresponded to that of exogenous rat PTH1-84 injection at doses between 3 and 10 ?g/kg. In conclusion, JTT-305 stimulated endogenous transient PTH secretion and bone formation, and consequently prevented bone loss in OVX rats. These results suggest that JTT-305 is orally active and has the potential to be an anabolic agent for the treatment of osteoporosis. PMID:21810422

Kimura, Shuichi; Nakagawa, Takashi; Matsuo, Yushi; Ishida, Yuji; Okamoto, Yoshihisa; Hayashi, Mikio

2011-10-01

299

Vitamin D insufficiency and effect of cholecalciferol in children with chronic kidney disease  

Microsoft Academic Search

Vitamin D insufficiency is common in patients with chronic kidney disease (CKD) and may contribute to mineral bone disease.\\u000a In a prospective interventional study, we estimated the prevalence of vitamin D insufficiency (serum 25-hydroxyvitamin D3\\u000a [25OHD] < 30 ng\\/ml), and examined the effect of high-dose (600,000 IU) cholecalciferol supplementation after 6 weeks on serum\\u000a 25OHD and parathyroid hormone (PTH) levels in children with

Pankaj Hari; Nandita Gupta; Smriti Hari; Ashima Gulati; Puneet Mahajan; Arvind Bagga

2010-01-01

300

Modification of the analysis of parathyroid hormone-related protein in milk and concentrations of this protein in commercial milk and milk products in Japan.  

PubMed

Parathyroid hormone-related protein (PTHrP), which causes hypercalcemia associated with malignant tumors, is known to be present in milk. Gene expression of PTHrP in the mammary gland increases markedly during parturition and with the onset of lactation. Even when circulating PTHrP levels are extremely low or below the detection limit, milk PTHrP levels are remarkably high. Parathyroid hormone-related protein derived from the mammary gland is assumed to play a role in maintaining the maternal calcium homeostasis and calcium transport from blood to milk. In previous studies that determined the PTHrP concentrations in milk, the pretreatments and diluent composition were not standardized. Here, we investigated the effect of various pretreatment procedures and diluent constitutions and the consequent PTHrP concentrations in commercial milk and milk products in Japan. Significant differences were found in PTHrP concentrations in raw milk samples subjected to different combinations of pretreatments (mixing, centrifugation, acidification, and heating) and diluents (0pM standard solution of PTHrP, plasma treated with protease inhibitors, and original diluent). We measured the PTHrP concentrations in normal liquid milk, processed milk, milk drinks, formulated milk powders, and skim milk powder by using the appropriate combination of pretreatment (acidification) and diluent (plasma treated with protease inhibitors). The PTHrP concentration in normal liquid milk, processed milk, and skim milk powder was as high as that in raw milk (>5nM), whereas that in milk drinks differed considerably. The PTHrP concentration in infant formulas (<2nM) was lower than that in the other milk products. These results indicate that a certain amount of PTHrP is ingested when milk and milk products are consumed. PMID:20412899

Onda, K; Yamaguchi, M; Ohashi, M; Sato, R; Ochiai, H; Iriki, T; Wada, Y

2010-05-01

301

A Novel Approach for High Level Expression of Soluble Recombinant Human Parathyroid Hormone (rhPTH 1-34) in Escherichia coli  

PubMed Central

Background Parathyroid hormone (PTH) secreted by parathyroid glands regulates the metabolism of calcium and phosphorus in bone and kidney. Thereby, it can stimulate bone formation, and is a promising agent in the treatment of osteoporosis. Mature form of PTH consists of 84 amino acids; however, the first 34 residues of PTH cover the majority of hormonal action. Methods In this study, the fusion form of highly soluble rhPTH was expressed at high level in Escherichia coli (E. coli). His6-thioredoxin as an extension for rhPTH improves the solubility of inclusion body. His6-thioredoxin-hPTH (1-34) was ligated into pET32a expression vector. The insertion of 5 amino acids (Asp-Asp-Asp-Asp-Lys) in the N-terminal of PTH made this protein to be digestable specifically by enterokinase enzyme. The fusion form of rhPTH was harvested and purified by immobilized affinity chromatography followed by digestion with enterokinase. Digested rhPTH was purified by applying on size exclusion and ion exchange chromatography to get the highest purity. Results The mass spectroscopy analysis shows rhPTH molecular weight was 4117.5 Da. The purity was measured by HPLC column which showed more than 97%. Bioassay analysis of rhPTH was performed on rat sarcoma cell UMR-106 in parallel with commercially available rhPTH, Forteo. The result was measured through immunofluorescence detection kit. The data showed that the potency of rhPTH was comparable with commercially available medicine. Conclusion Thioredoxin was applied as a fusion partner for production of highly soluble rhPTH. This specific fusion partner increased protein solubility and decreased protease reactivity. Purification process was optimized for high recovery and for purity more than 99%. As its biological activity is comparable with marketed drug, this protein is qualified for biopharmaceutical usage. PMID:23919123

Hamedifar, Haleh; Salamat, Firoozeh; Saffarion, Mohammad; Ghiasi, Mohammad; Hosseini, Alireza; Lahiji, Hadi; Nouri, Zomorrod; Arfae, Hamed; Mahboudi, Fereidoun

2013-01-01

302

Impaired Vitamin D Metabolism in CKD  

PubMed Central

Vitamin D metabolism consists of both production and catabolism, which are enzymatically driven and highly regulated. Renal vitamin D metabolism requires filtration and tubular reabsorption of 25-hydroxyvitamin D and is regulated by parathyroid hormone, fibroblast growth factor-23, and 1,25-dihydroxyvitamin D. In CKD, renal production of1,25-dihydroxyvitamin D from 25-hydroxyvitamin D is reduced. In addition, pharmacokinetic studies and epidemiologic studies of 24,25-dihydroxyvitamin D, the most abundant product of 25-hydroxyvitamin D catabolism by CYP24A1, suggest that vitamin D catabolism is also reduced. New insights into the mechanisms and regulation of vitamin D metabolism may lead to novel approaches to assess and treat impaired vitamin D metabolism in CKD. PMID:23465502

Bosworth, Cortney; de Boer, Ian H.

2013-01-01

303

Vitamins  

MedlinePLUS

... helps you see at night. Vitamin C in oranges helps your body heal if you get a ... vitamin A? milk fortified with vitamin A liver orange fruits and vegetables (like cantaloupe, carrots, sweet potatoes) ...

304

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 ...

305

Identification, molecular characterization, and tissue expression of parathyroid hormone-related protein gene (PTHrP) from water buffalo (Bubalus bubalis).  

PubMed

Parathyroid hormone-related protein (PTHrP) is involved in the deposition of milk calcium in mammal lactation, but its role in buffalo is unclear. In this study, the full-length coding sequence of the water buffalo PTHrP gene was first isolated using reverse transcription-polymerase chain reaction. The protein was then subjected to molecular characterization using bioinformatic methods, and the tissue expression pattern was further assayed by semi-quantitative reverse-transcription polymerase chain reaction. The water buffalo PTHrP gene contains an open reading frame of 534 base pairs encoding a polypeptide of 177 amino acid residues, a theoretical molecular weight of 20.32 kDa, and an isoelectric point of 10.00. In addition, water buffalo PTHrP was predicted to contain a signal peptide, a typical hydrophobic region with no hydrophobic transmembrane regions, and to exert its function in the cell nucleus. A conserved domain of parathyroid superfamily from amino acids 34-114 was observed in the polypeptide. Sequence comparison and the phylogenetic analysis showed that the sequence of the water buffalo PTHrP protein shared high homology with that of other mammals, particularly cattle and goat. Among the 16 tissues examined, the PTHrP gene was only expressed in adipose tissue, placenta, uterine wall, hypophysis, and mammary gland tissue, but gene expression levels were higher in the uterus wall and adipose tissue. The results of this study suggest that the PTHrP gene plays an important role in the deposition of milk calcium of water buffalo. PMID:25867375

Liu, J; Qian, L D; Huo, J L; Bi, B L; Li, D L; Wang, S F; Chen, T; Li, L J; Mao, H M; Miao, Y W

2015-01-01

306

An Interesting Case of Life-Threatening Hypercalcemia Secondary to Atypical Parathyroid Adenoma versus Parathyroid Carcinoma  

PubMed Central

Context. Severe hypercalcemia is a life-threatening condition. Atypical parathyroid adenoma and parathyroid carcinomas are uncommon causes which can be difficult to differentiate. Objective. We report a case of a 36-year-old male with very high serum calcium due to a possible atypical parathyroid adenoma versus parathyroid carcinoma. Case Illustration. A serum calcium level of 23.2?mg/dl was noted on admission. He was initially treated with IV hydration, pamidronate, and salmon calcitonin to lower his calcium levels. He also underwent a surgical en bloc resection of parathyroid mass. Pathology showed a mixed picture consistent with possible atypical adenoma versus parathyroid carcinoma. However, due to the possible involvement of the recurrent laryngeal nerve, parathyroid carcinoma was more likely. Also after operation the patient developed hungry bones syndrome and his calcium was replaced vigorously. He continues to be on calcium, vitamin D, and calcitriol supplementation. Results. A review of the literature was conducted to identify previous studies pertaining to parathyroid adenomas and parathyroid cancer. Conclusion. We thereby conclude that hypercalcemia requires very careful monitoring especially after operation. Also it can be very difficult to distinguish between atypical parathyroid adenomas and parathyroid carcinomas as in our case and no clear cut guidelines yet exist to differentiate the two based on histology. PMID:24959180

Mishra, Ankur; Newman, David

2014-01-01

307

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

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

M Kneissel; A Boyde; J. A Gasser

2001-01-01

308

Amphibian parathyroids: morphological and functional aspects.  

PubMed

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

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

1995-10-01

309

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

PubMed Central

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

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

2013-01-01

310

[Intraoperative management of undetectable parathyroid adenoma].  

PubMed

Despite new technologies and progress in parathyroid gland imaging, missed parathyroid adenomas are still a problem. In reoperations most adenomas were found in eutopic positions. Adenoma in atypical positions were mostly situated in the thymus or in the esophageal-tracheal groove. Positive parathyroid imaging can be helpful but does not necessarily result in a better success rate than conventional bilateral exploration by an experienced surgeon, which is >?95?%. The knowledge of anatomy and embryological development of parathyroid glands is most important. Intraoperative determination of parathyroid hormone levels can help localize the site of the adenoma. Thyroid resection should only be performed if preoperative or intraoperative ultrasound indicates a tumor in the thyroid gland. The most important factor for a successful parathyroid operation is an experienced surgeon. PMID:25591414

Dotzenrath, C

2015-01-01

311

Black bear parathyroid hormone has greater anabolic effects on trabecular bone in dystrophin-deficient mice than in wild type mice.  

PubMed

Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disease that has deleterious consequences in muscle and bone, leading to decreased mobility, progressive osteoporosis, and premature death. Patients with DMD experience a higher-than-average fracture rate, particularly in the proximal and distal femur and proximal tibia. The dystrophin-deficient mdx mouse is a model of DMD that demonstrates muscle degeneration and fibrosis and osteoporosis. Parathyroid hormone, an effective anabolic agent for post-menopausal and glucocorticoid-induced osteoporosis, has not been explored for DMD. Black bear parathyroid hormone (bbPTH) has been implicated in the maintenance of bone properties during extended periods of disuse (hibernation). We cloned bbPTH and found 9 amino acid residue differences from human PTH. Apoptosis was mitigated and cAMP was activated by bbPTH in osteoblast cultures. We administered 28nmol/kg of bbPTH 1-84 to 4-week old male mdx and wild type mice via daily (5×/week) subcutaneous injection for 6 weeks. Vehicle-treated mdx mice had 44% lower trabecular bone volume fraction than wild type mice. No changes were found in femoral cortical bone geometry or mechanical properties with bbPTH treatment in wild type mice, and only medio-lateral moment of inertia changed with bbPTH treatment in mdx femurs. However, ?CT analyses of the trabecular regions of the distal femur and proximal tibia showed marked increases in bone volume fraction with bbPTH treatment, with a greater anabolic response (7-fold increase) in mdx mice than wild type mice (2-fold increase). Trabecular number increased in mdx long bone, but not wild type bone. Additionally, greater osteoblast area and decreased osteoclast area were observed with bbPTH treatment in mdx mice. The heightened response to PTH in mdx bone compared to wild type suggests a link between dystrophin deficiency, altered calcium signaling, and bone. These findings support further investigation of PTH as an anabolic treatment for DMD-induced osteoporosis. PMID:22584007

Gray, Sarah K; McGee-Lawrence, Meghan E; Sanders, Jennifer L; Condon, Keith W; Tsai, Chung-Jui; Donahue, Seth W

2012-09-01

312

In vitro and in vivo effect of parathyroid hormone analogue (1-14) containing -amino-iso-butyric acid residue (Aib)1,3.  

PubMed

Firstly, parathyroid hormone (1-14) [PTH (1-14)] analogue containing various -amino-iso-butyric acid residue (Aib) was synthesized by exchanging the 1st and 3rd Ala residues of alpha carbon of PTH (1-14). This analogue revealed to have the quite tight and stable -helical structure using the nuclear magnetic resonance (NMR) analysis. The biological activities of these analogues were examined using a cAMP- generating assay in LLC-PK1 cell lines stably transfected with the wild- type human PTH1 receptor. Only the PTH analogue substituted with methyl moiety without acetylation showed significant cAMP generating action with 15.0 +/- 3.414 of EC50. Then, we used an ovariectomized rat model system to compare the in vivo effects of parathyroid hormone analogue with that of PTH (1-84). Daily subcutaneous administration of the unacetylated Aib1,3PTH (1-14) for 5 weeks in 30 nM/kg subcutaneously with positive control group receiving PTH (1-84) with 8 nM/ kg were performed. However, there was no significant change in spinal or femoral bone mineral density assessed by dual x-ray absorptiometry (DXA) in the Aib1,3PTH (1-14) group where definite increase of these parameters shown in the PTH (1-84) group (p < 0.001). Assessment of bone strength was evaluated with no significant differences among all groups. It was quite disappointing to see the actual discrepancies between the result of significant pharmacokinetic potency and the in vivo clinical effect of the Aib1,3PTH (1-14). However, there are several limitations to mention, such as the short duration of treatment, matter of dosage, and insufficient effect of tight -helical structures with absence of C-terminus. In conclusion, our findings suggest that unacetylated Aib1,3PTH (1-14) did not exhibit any anabolic effects at the bones of ovariectomized rats. PMID:16642551

Rhee, Yumie; Lee, Weontae; Lee, Eun Jin; Ma, Suhyun; Park, So Young; Lim, Sung-Kil

2006-04-30

313

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

NSDL National Science Digital Library

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

2002-01-01

314

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

PubMed Central

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

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

2013-01-01

315

Characterization of PHEX endopeptidase catalytic activity: identification of parathyroid-hormone-related peptide107-139 as a substrate and osteocalcin, PPi and phosphate as inhibitors.  

PubMed Central

Mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) are responsible for X-linked hypophosphataemia, and studies in the Hyp mouse model of the human disease implicate the gene product in the regulation of renal phosphate (P(i)) reabsorption and bone mineralization. Although the mechanism for PHEX action is unknown, structural homologies with members of the M13 family of endopeptidases suggest a function for PHEX protein in the activation or degradation of peptide factors involved in the control of renal P(i) transport and matrix mineralization. To determine whether PHEX has endopeptidase activity, we generated a recombinant soluble, secreted form of human PHEX (secPHEX) and tested the activity of the purified protein with several peptide substrates, including a variety of bone-related peptides. We found that parathyroid-hormone-related peptide(107-139) is a substrate for secPHEX and that the enzyme cleaves at three positions within the peptide, all located at the N-terminus of aspartate residues. Furthermore, we show that osteocalcin, PP(i) and P(i), all of which are abundant in bone, are inhibitors of secPHEX activity. Inhibition of secPHEX activity by osteocalcin was abolished in the presence of Ca(2+). We suggest that PHEX activity and mineralization may be controlled in vivo by PP(i)/P(i) and Ca(2+) and, in the latter case, the regulation requires the participation of osteocalcin. PMID:11311133

Boileau, G; Tenenhouse, H S; Desgroseillers, L; Crine, P

2001-01-01

316

Identification of a cDNA encoding a parathyroid hormone-like peptide from a human tumor associated with humoral hypercalcemia of malignancy  

SciTech Connect

Humoral hypercalcemia of malignancy is a common paraneoplastic syndrome that appears to be mediated in many instances by a parathyroid hormone-like peptide. Poly(A)/sup +/ RNA from a human renal carcinoma associated with this syndrome was enriched by preparative electrophoresis and used to construct an enriched cDNA library in phage lambdagt10. The library was screened with a codon-preference oligonucleotide synthesized on the basis of a partial N-terminal amino acid sequence from a human tumor-derived peptide, and a 2.0 kilo-base cDNA was identified. The cDNA encodes a 177 amino acid protein consisting of a 36 amino acid leader sequence and a 141 amino acid mature peptide. The first 13 amino acids of the deduced sequence of the mature peptide display strong homology to human PTH, with complete divergence thereafter. RNA blot-hybridization analysis revealed multiple transcripts in mRNA from tumors associated with the humor syndrome and also in mRNA from normal human keratinocytes. Southern blot analysis of genomic DNA from humans and rodents revealed a simple pattern compatible with a single-copy gene. The gene has been mapped to chromosome 12.

Mangin, M.; Webb, A.C.; Dreyer, B.E.; Posillico, J.T.; Ikeda, K.; Weir, E.C.; Stewart, A.F.; Bander, N.H.; Milstone, L.; Barton, D.E.

1988-01-01

317

Parathyroid hormone (PTH)/PTH-related peptide type 1 receptor (PPR) signaling in osteocytes regulates anabolic and catabolic skeletal responses to PTH.  

PubMed

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

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

2013-07-12

318

Parathyroid hormone-related protein (107-111) improves the bone regeneration potential of gelatin-glutaraldehyde biopolymer-coated hydroxyapatite.  

PubMed

Biopolymer-coated nanocrystalline hydroxyapatite (HA) made as macroporous foams which are degradable and flexible are promising candidates as orthopaedic implants. The C-terminal (107-111) epitope of parathyroid hormone-related protein (PTHrP) exhibits osteogenic properties. The main aim of this study was to evaluate whether PTHrP (107-111) loading into gelatin-glutaraldehyde biopolymer-coated HA (HAGlu) scaffolds would produce an optimal biomaterial for tissue engineering applications. HAGlu scaffolds with and without PTHrP (107-111) were implanted into a cavitary defect performed in both distal tibial metaphysis of adult rats. Animals were sacrificed after 4 weeks for histological, microcomputerized tomography and gene expression analysis of the callus. At this time, bone healing occurred only in the presence of PTHrP (107-111)-containing HAGlu implant, related to an increase in bone volume/tissue volume and trabecular thickness, cortical thickness and gene expression of osteocalcin and vascular cell adhesion molecule 1, but a decreased gene expression of Wnt inhibitors, SOST and dickkopf homolog 1. The autonomous osteogenic effect of the PTHrP (107-111)-loaded HAGlu scaffolds was confirmed in mouse and human osteoblastic cell cultures. Our findings demonstrate the advantage of loading PTHrP (107-111) into degradable HAGlu scaffolds for achieving an optimal biomaterial that is promising for low load bearing clinical applications. PMID:24704694

Lozano, Daniel; Sánchez-Salcedo, Sandra; Portal-Núñez, Sergio; Vila, Mercedes; López-Herradón, Ana; Ardura, Juan Antonio; Mulero, Francisca; Gómez-Barrena, Enrique; Vallet-Regí, María; Esbrit, Pedro

2014-07-01

319

Nucleotide sequence analysis of CDR3 elements of a panel of anti-peptide monoclonal antibodies recognizing parathyroid hormone-related protein.  

PubMed Central

Nucleotide sequences of heavy (VH) and light (VL) chain variable region complementarity determining regions have been determined from in vitro amplified mRNA isolated from a panel of monoclonal antibodies (mAb) raised to a synthetic 34mer peptide representing the N-terminal portion of human parathyroid hormone-related protein (PTHrP or parathyrin) reported to contain an immunodominant epitope. These mAb vary in affinity for the synthetic peptide and native PTHrP (Ka between 5.9 x 10(8) and 1.9 x 10(11)l/M). All 10 mAb studied were found were found to utilized restricted VH2, V kappa 2, JH4 and J kappa 1 family genes. Significant differences in the length and sequence of D elements were found; however 9/10 mAb utilize members of the DSP2 family. Significantly, two broad ranges of affinity could be determined based on the presence of Asp or Ala at residue 101 in JH. Images Figure 2 PMID:8478021

Rapley, R; Flora, P S; Walsh, D J; Walker, M R

1993-01-01

320

Effects of parathyroid hormone and calcitonin on Na+, Cl-, K+, Mg2+ and Ca2+ transport in cortical and medullary thick ascending limbs of mouse kidney.  

PubMed

The effect of parathyroid hormone (PTH) on transepithelial Na+, Cl-, K+, Ca2+ and Mg2+ transport was investigated in isolated perfused cortical thick ascending limbs (cTAL) and that of human calcitonin (hCT) was tested in both cortical and medullary thick ascending limbs (mTAL) of the mouse nephron. The transepithelial ion net fluxes (Jx) were determined by electron probe analysis of the perfused and collected fluids. Simultaneously, the transepithelial voltage (PDte) and resistance (Rte) were recorded. In cTAL segments, PTH and hCT significantly stimulated the reabsorption of Na+, Cl-, Ca2+ and Mg2+, hCT generated a net K+ secretion towards the lumen and PTH tended to exert the same effect. Neither PDte nor Rte were significantly altered by either PTH or hCT. However, in the post-experimental period a significant decrease in PDte was noted. Time control experiments carried out under similar conditions revealed a significant decrease in PDte with time, which could have masked the hormonal response. In mTAL segments, Mg2+ and Ca2+ transport was close to zero, hCT did not exert any detectable effect on either PDte or Jcl-, JNa+, JK+, JMg2+ and JCa2+ in these segments. In conclusion, our data demonstrate that PTH and hCT stimulate NaCl reabsorption as well as Mg2+ and Ca2+ reabsorption in the cTAL segment of the mouse. These data are in agreement with and extend data obtained in vivo in the rat. PMID:2084613

Di Stefano, A; Wittner, M; Nitschke, R; Braitsch, R; Greger, R; Bailly, C; Amiel, C; Roinel, N; de Rouffignac, C

1990-10-01

321

Parathyroid disorders of pregnancy.  

PubMed

Diseases of the parathyroid gland are uncommon in women of childbearing age. However, total serum calcium is lower in normal pregnancy, but ionized serum calcium remains within normal limits. Serum parathyroid levels are slightly decreased in the second half of pregnancy. Primary hyperparathyroidism, if unrecognized, may increase maternal and fetal morbidity, which is related to the level of serum calcium. The most common cause is a single parathyroid adenoma, accounting for about 80% of cases. Maternal complications include acute pancreatitis, hypercalcemia crisis, and toxemia. An increased incidence of prematurity and neonatal hypocalcemia has been reported when maternal hypercalcemia is significantly elevated. Other causes of hypercalcemia are rare in pregnancy. Hypoparathyroidism is seldom seen in pregnancy; the most common cause is after surgical throidectomy. The doses of vitamin D and calcium do not change during pregnancy; however, hypercalcemia may develop in the postpartum period. Serum calcium should be determined at every trimester of pregnancy and at regular intervals after delivery, and in a significant number of patients, the dose of vitamin D should be reduced. Osteoporosis has been recognized most frequently in the last few years. It appears that those patients with a family history of osteoporosis and those on heparin therapy have a tendency to develop symptoms of the disease in pregnancy. Finally, lactation is not contraindicated in women with osteoporosis; although there is a slight decrease in bone density in the few months after delivery, this is a transient event and bone densitometry returns to prepregnancy levels in most women. Recent studies indicate that there is no need for calcium therapy during lactation with few exceptions, such as lactating adolescents, mothers nursing more than one child, and mothers with closely-spaced pregnancies. PMID:9880118

Mestman, J H

1998-12-01

322

Effects of Gonadal Suppression on the Regulation of Parathyroid Hormone and 1,25-Dihydroxyvitamin D Secretion in Women  

Microsoft Academic Search

Although a causal association between estrogen deficiency and bone loss has been established for many years, the mechanism by which estrogen deficiency leads to bone loss is unclear. Estrogen deficiency could induce bone loss either by a direct effect on bone cells to modify the production of bone-resorbing cytokines or by altering the production or response to calcium regulatory hormones

JOEL S. FINKELSTEIN; DAVID A. SCHOENFELD

323

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

PubMed Central

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

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

2013-01-01

324

Relationship Between Disease Activity and Serum Levels of Vitamin D Metabolites and Parathyroid Hormone in Ankylosing Spondylitis  

Microsoft Academic Search

:   Vertebral fractures due to osteoporosis are a common but frequently unrecognized complication of ankylosing spondylitis (AS)\\u000a and various factors may contribute to the development of osteoporosis in AS. It is known that inflammatory activity in rheumatic\\u000a disease (i.e., proinflammatory cytokines) itself plays a possible role in the pathophysiology of bone loss. 1,25-Dihydroxyvitamin\\u000a D3 (1,25(OH)2D3) seems to be another possible

U. Lange; O. Jung; J. Teichmann; G. Neeck

2001-01-01

325

A Global Study of Vitamin D Status and Parathyroid Function in Postmenopausal Women with Osteoporosis: Baseline Data from the Multiple Outcomes of Raloxifene Evaluation Clinical Trial  

Microsoft Academic Search

Vitamin D deficiency leads to secondary hyperparathyroidism, in- creased bone turnover, and bone loss and, when severe, to osteoma- lacia. Vitamin D deficiency is common in elderly people, especially the institutionalized. The definition of vitamin D deficiency is hampered by the fact that large interlaboratory differences exist in assays for serum 25-hydroxyvitamin D (25OHD), the main circulating metab- olite. The

PAUL LIPS; TU DUONG; ANNA OLEKSIK; DENNIS BLACK; STEVEN CUMMINGS; DAVID COX; THOMAS NICKELSEN

326

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

PubMed

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

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

2015-01-01

327

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

PubMed Central

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

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

2013-01-01

328

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

PubMed Central

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

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

2011-01-01

329

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

PubMed

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

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

2011-03-18

330

In vitro regulation of proliferation and differentiation within a postnatal growth plate of the cranial base by parathyroid hormone-related peptide (PTHrP).  

PubMed

Parathyroid hormone-related peptide (PTHrP) is known to be an important regulator of chondrocyte differentiation in embryonic growth plates, but little is known of its role in postnatal growth plates. The present study explores the role of PTHrP in regulating postnatal chondrocyte differentiation using a novel in vitro organ culture model based on the ethmoidal growth plate of the cranial base taken from the postnatal day 10 mouse. In vitro the ethmoidal growth plate continued to mineralize and the chondrocytes progressed to hypertrophy, as observed in vivo, but the proliferative zone was not maintained. Treatment with PTHrP inhibited mineralization and reduced alkaline phosphatase (ALP) activity in the hypertrophic zone in the ethmoidal growth plates grown ex vivo, and also increased the proliferation of non-hypertrophic chondrocytes. In addition, exogenous PTHrP reduced the expression of genes associated with terminal differentiation: type X collagen, Runx2, and ALP, as well as the PTH/PTHrP receptor (PPR). Activation of the protein kinase A pathway using 8-Br-cAMP mimicked some of these pro-proliferative/anti-differentiative effects of PTHrP. PTHrP and PPR were found to be expressed within the ethmoidal growth plate using semi-quantitative PCR, and in other cranial growth plates such as the spheno-occipital and pre-sphenoidal synchondroses. These results provide the first functional evidence that PTHrP regulates proliferation and differentiation within the postnatal, cranial growth plate. J. Cell. Physiol. 219: 688-697, 2009. (c) 2009 Wiley-Liss, Inc. PMID:19229881

Wealthall, Rosamund J

2009-06-01

331

Serum Parathyroid Hormone and 25?Hydroxyvitamin D Concentrations and Risk of Incident Heart Failure: The Multi?Ethnic Study of Atherosclerosis  

PubMed Central

Background Heart failure (HF) is common and is associated with high mortality. We aimed to determine associations of serum parathyroid hormone (PTH) and 25?hydroxyvitamin D (25[OH]D) with incident HF and left ventricular mass. Methods and Results Among 6459 participants in the community?based Multi?Ethnic Study of Atherosclerosis, all of whom were free of prevalent clinical cardiovascular disease, we measured serum concentrations of PTH and 25(OH)D at the baseline examination. In longitudinal analyses, we tested associations of PTH and 25(OH)D with incident HF events, adjudicated by a panel of physicians. In cross?sectional analyses of a subset of 4763 participants, we tested associations of PTH and 25(OH)D with left ventricular mass, measured by cardiac magnetic resonance imaging at baseline. Multivariable Cox proportional hazard and linear regression models were adjusted for demographics, physical examination measures, comorbidity, kidney function, and other mineral metabolism markers. Mean age was 62 years and 53% of participants were female. There were 180 incident HF events over a median (interquartile range) follow?up time of 8.46 (7.67 to 8.63) years. Compared with participants with PTH <65 pg/mL, PTH ?65 pg/mL was associated with a 50% greater risk of incident HF (95% CI: 3% to 210%) and a 5.3 g higher left ventricular mass (95% CI: 2.6, 7.9 g). In contrast, there was no association of 25(OH)D with risk of incident HF or elevated left ventricular mass. Conclusions In a racially/ethnically diverse population without prevalent cardiovascular disease, higher serum PTH concentration was associated with increased left ventricular mass and increased risk of incident HF. Further studies should be pursued to determine whether PTH excess may be a modifiable risk factor for HF. PMID:25468653

Bansal, Nisha; Zelnick, Leila; Robinson?Cohen, Cassianne; Hoofnagle, Andy N.; Ix, Joachim H.; Lima, Joao A.; Shoben, Abigail B.; Peralta, Carmen A.; Siscovick, David S.; Kestenbaum, Bryan; de Boer, Ian H.

2014-01-01

332

The effects of excipients and particle engineering on the biophysical stability and aerosol performance of parathyroid hormone (1-34) prepared as a dry powder for inhalation.  

PubMed

Pulmonary delivery of therapeutic peptides and proteins has many advantages including high relative bioavailability, rapid systemic absorption and onset of action and a non-invasive mode of administration which improves patient compliance. In this study, we investigated the effect of spray-drying (SD) and spray freeze-drying processes on the stability and aerosol performance of parathyroid hormone (PTH) (1-34) microparticles. In this study, the stabilisation effect of trehalose (a non-reducing sugar) and Brij 97 (a non-ionic surfactant) on spray-dried PTH particles was assessed using analytical techniques including circular dichroism (CD), fluorescence spectroscopy, modulated differential scanning calorimetry and an in vitro bioactivity assay. Physical characterisation also included electron microscopy, tap density measurement and laser light diffraction. The aerosol aerodynamic performance of the formulations was assessed using the Andersen cascade impactor. Based on these studies, a formulation for spray freeze-drying was selected and the effects of the two particle engineering techniques on the biophysical stability and aerosol performance of the resulting powders was determined. CD, fluorescence spectroscopy and bioactivity data suggest that trehalose when used alone as a stabilising excipient produces a superior stabilising effect than when used in combination with a non-ionic surfactant. This highlights the utility of CD and fluorescence spectroscopy studies for the prediction of protein bioactivity post-processing. Therefore, a method and formulation suitable for the preparation of PTH as a dry powder was developed based on spray-drying PTH with trehalose as a stabiliser with the bioactivity of SD PTH containing trehalose being equivalent to that of unprocessed PTH. PMID:21271316

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

2011-03-01

333

Induction of parathyroid hormone-related peptide by the Ras oncogene: role of Ras farnesylation inhibitors as potential therapeutic agents for hypercalcemia of malignancy.  

PubMed

Parathyroid hormone related peptide (PTHRP) is the major causal agent in the syndrome of malignancy-associated hypercalcemia (MAH). Several studies have shown that PTHRP production is increased in response to growth factors and oncogenes, such as Tpr-Met, that are associated with the tyrosine kinase signaling pathway. Using site-directed mutagenesis of Tpr-Met and chemical inhibitors of phosphotidylinositol-3 kinase and Ras isoprenylation, we demonstrated previously that induction of PTHRP is mediated via the Ras signaling pathway. In the present study, we have directly investigated the role of the Ras oncogene in MAH. As a model system, we used Fisher rat 3T3 fibroblasts stably transfected with a Ras oncogene (Ras-3T3). Ras transfection enhanced PTHRP production 5-10-fold in these cells, and inoculation of this cell line into nude mice led to the development of hypercalcemia within 2 weeks. We used this system to evaluate the effect of a potent inhibitor of Ras processing, B-1086, on cell growth, PTHRP production, plasma calcium, and tumor growth. Treatment of Ras-3T3 cells in vitro with B-1086 at 0.1-10 microg/ml produced a significant reduction in PTHRP mRNA expression and PTHRP secretion and a significant decrease in cell proliferation. Treatment in vivo of BALB/c/nu/nu mice bearing Ras-3T3 tumors with B-1086 resulted in a significant inhibition in tumor growth. In addition, this treatment produced near normalization of serum Ca2+, a significant decrease in plasma PTHRP, and a reduction in tumoral PTHRP mRNA levels. These results show that the Ras pathway is involved in PTHRP production by tumors, identifies Ras as a potential target for treatment of MAH, and demonstrates Ras processing inhibitors as candidate therapeutic agents against this syndrome. PMID:9377563

Aklilu, F; Park, M; Goltzman, D; Rabbani, S A

1997-10-15

334

Parathyroid-hormone variance is only marginally explained by a panel of determinants: a cross-sectional study of 909 hip-fracture patients.  

PubMed

Several factors affect the levels of parathyroid hormone (PTH) in hip-fracture patients. We hypothesized that a panel of easily assessable determinants could account for both a substantial proportion of PTH variance and the occurrence of secondary hyperparathyroidism. We evaluated 909 of 981 hip-fracture inpatients admitted consecutively to our Rehabilitation division. In each patient we assessed PTH, 25-hydroxyvitamin D, albumin-adjusted total calcium, phosphate, magnesium, and creatinine on a fasting blood sample 21.3 ± 6.1 (mean ± SD) days after fracture occurrence. Glomerular filtration rate (GFR) was estimated by the 4-variable Modification of Diet in Renal Disease Study equation. Functional level was assessed using the Barthel index. On multivariate analysis, six factors (phosphate, albumin-adjusted total calcium, estimated GFR (eGFR), 25-hydroxyvitamin D, age, and magnesium) were significantly associated with PTH levels. Overall, the panel of variables accounted for 23.7 % of PTH variance. Among the 909 patients, 304 (33.4 %) had PTH levels exceeding the normal range. Six factors (phosphate, albumin-adjusted total calcium, eGFR, 25-hydroxyvitamin D, age, and Barthel index scores) were significantly associated with the category of PTH level (either normal or elevated). The model correctly classified 70.4 % of cases. For the optimal cut-off point, sensitivity was 80 % and specificity was 61 %. Data shows that six factors were significantly associated with PTH levels in hip-fracture inpatients. However, the six factors accounted for only 23.7 % of PTH variance and the presence or absence of secondary hyperparathyroidism was correctly categorized in a modest proportion of cases. We conclude that more knowledge is needed on the factors affecting PTH levels after hip fracture. PMID:24202062

Di Monaco, Marco; Castiglioni, Carlotta; Vallero, Fulvia; Di Monaco, Roberto; Tappero, Rosa

2014-09-01

335

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

NASA Technical Reports Server (NTRS)

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

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

2001-01-01

336

Human renal carcinoma expresses two messages encoding a parathyroid hormone-like peptide: Evidence for the alternative splicing of a single-copy gene  

SciTech Connect

A peptide secreted by tumors associated with the clinical syndrome of humoral hypercalcemia of malignancy was recently purified from human renal carcinoma cell line 786-0. The N-terminal amino acid sequence of this peptide has considerable similarity with those of parathyroid hormone (PTH) and of peptides isolated from human breast and lung carcinoma (cell line BEN). In this study the authors obtained the nucleotide sequence of a 1595-base cDNA complementary to mRNA encoding the PTH-like peptide produced by 786-0 cells. The cDNA contains an open reading frame encoding a leader sequence of 36 amino acids and a 139-residue peptide, in which 8 of the first 13 residues are identical to the N terminus of PTH. Through the first 828 bases the sequence of this cDNA is identical with one recently isolated from a BEN cell cDNA library; however, beginning with base 829 the sequences diverge, shortening the open reading frame by 2 amino acids. Differential RNA blot analysis revealed that 786-0 cells express two major PTH-like peptide mRNAs with different 3{prime} untranslated sequences, one of which hybridizes with the presently described sequence and the other one with that reported for the BEN cell PTH-like peptide cDNA. Primer-extension analysis of 786-0 poly(A){sup +} RNA together with Southern blot analysis of human DNA confirmed the presence of a single-copy gene coding for multiple mRNAs through alternate splicing. In addition, the 3{prime} untranslated sequence of the cDNA described here has significant similarity to the c-myc protooncogene.

Thiede, M.A.; Strewler, G.J.; Nissenson, R.A.; Rosenblatt, M.; Rodan, G.A. (Merck Sharp Dohme Research Labs., West Point, PA (USA))

1988-07-01

337

Parathyroid hormone linked to a collagen binding domain promotes hair growth in a mouse model of chemotherapy-induced alopecia in a dose-dependent manner.  

PubMed

Chemotherapy-induced alopecia is a major source of psychological stress in patients undergoing cancer chemotherapy, and it can influence treatment decisions. Although there is currently no therapy for alopecia, a fusion protein of parathyroid hormone and collagen binding domain (PTH-CBD) has shown promise in animal models. The aim of this study was to determine whether there are dose-dependent effects of PTH-CBD on chemotherapy-induced alopecia in a mouse model. C57BL/6J mice were waxed to synchronize hair follicles; treated on day 7 with vehicle or PTH-CBD (100, 320, and 1000 mcg/kg subcutaneous injection); and treated on day 9 with vehicle or cyclophosphamide (150 mg/kg intraperitoneally). Mice were photographed every 3-4 days and killed on day 63 for histological analysis. Photographs were quantified by gray scale analysis to assess hair content. Mice not receiving chemotherapy showed regrowth of hair 2 weeks after waxing and normal histology after 2 months. Mice receiving chemotherapy alone showed marked hair loss after chemotherapy, which was sustained for 10 days and was followed by rapid regrowth of a normal coat. Histological analysis revealed rapid cycling dystrophic anagen/catagen follicles. Animals receiving chemotherapy and PTH-CBD showed decreased hair loss and more rapid regrowth of hair than that seen with chemotherapy alone (increased hair growth by gray scale analysis, P<0.05), and the effects were dose dependent. Histologically, hair follicles in animals receiving the highest dose of PTH-CBD were in a quiescent phase, similar to that in mice that did not receive chemotherapy. Single-dose subcutaneous administration of PTH-CBD showed dose-dependent effects in minimizing hair loss and speeding up recovery from chemotherapy-induced alopecia. PMID:24710191

Katikaneni, Ranjitha; Ponnapakkam, Tulasi; Seymour, Andrew; Sakon, Joshua; Gensure, Robert

2014-08-01

338

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

PubMed

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

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

2014-11-01

339

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

PubMed

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% FBS. Insulin (10 micrograms/ml) induced chondrogenic differentiation of the cells in a postconfluent phase through a cellular condensation process, resulting in the formation of cartilage nodules, as evidenced by expression of type II collagen and aggrecan genes. We found that differentiated cultures of ATDC5 cells abundantly expressed the high affinity receptor for PTH (Mr approximately 80 kD; Kd = 3.9 nM; 3.2 x 10(5) sites/cell). The receptors on differentiated cells were functionally active, as evidenced by a PTH-dependent activation of adenylate cyclase. Specific binding of PTH to cells markedly increased with the formation of cartilage nodules, while undifferentiated cells failed to show specific binding of PTH. Northern blot analysis indicated that expression of the PTH/PTHrP receptor gene became detectable at the early stage of chondrogenesis of ATDC5 cells, preceding induction of aggrecan gene expression. Expression of the PTH/PTHrP receptor gene was undetectable in undifferentiated cells. The level of PTH/PTHrP receptor mRNA was markedly elevated parallel to that of type II collagen mRNA. These lines of evidence suggest that the expression of functional PTH/PTHrP receptor is associated with the onset of chondrogenesis. In addition, activation of the receptor by exogenous PTH or PTHrP significantly interfered with cellular condensation and the subsequent formation of cartilage nodules, suggesting a novel site of PTHrP action. PMID:8609176

Shukunami, C; Shigeno, C; Atsumi, T; Ishizeki, K; Suzuki, F; Hiraki, Y

1996-04-01

340

Velcalcetide (AMG 416), a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects  

PubMed Central

Context Velcalcetide, also known as AMG 416, is a novel, long-acting selective peptide agonist of the calcium sensing receptor. It is being developed as an intravenous treatment of secondary hyperparathyroidism (SHPT) in hemodialysis patients with chronic kidney disease—mineral and bone disorder. Objective To assess the safety, tolerability, pharmacokinetics and pharmacodynamics of velcalcetide in healthy male volunteers. Methods The study was a double-blind, randomized, placebo-controlled, single-dose, dose-escalation study in healthy males aged 18–45 years conducted at a single center. Each cohort included eight subjects randomized 6:2 to velcalcetide or placebo. Intervention Velcalcetide at 0.5, 2, 5 and 10 mg or placebo was administered intravenously. Outcomes Measurements included plasma ionized calcium (iCa), serum total calcium, intact parathyroid hormone (iPTH), phosphorus and fibroblast growth factor-23 (FGF23), 1,25-dihydroxyvitamin D, calcitonin and urine creatinine, calcium and phosphorus and plasma pharmacokinetics for velcalcetide. Vital signs, safety biochemical and hematological indices, and adverse events were monitored throughout the study. Results Intravenous administration of velcalcetide was well tolerated with no adverse reaction of nausea, vomiting or diarrhea reported. Velcalcetide mediated dose-dependent decreases in serum iPTH at 30 min, FGF23 at 24 h and iCa at 12 h post dose (P < 0.05) and in urine fractional excretion of phosphorus and increases in tubular reabsorption of phosphorus. Velcalcetide plasma exposure increased in a dose-related manner and the terminal elimination of half-life was comparable across the dose range evaluated and ranged from 18.4 to 20.0 h. Conclusion Single IV doses of velcalcetide were well tolerated and associated with rapid, sustained, dose-dependent reductions in serum PTH. The results support further evaluation of velcalcetide as a treatment for SHPT in hemodialysis patients. PMID:24235081

Martin, Kevin J.; Bell, Gregory; Pickthorn, Karen; Huang, Saling; Vick, Andrew; Hodsman, Peter; Peacock, Munro

2014-01-01

341

Intermittent administration of human parathyroid hormone enhances bone formation and union at the site of cancellous bone osteotomy in normal and ovariectomized rats.  

PubMed

Intermittent administration of human parathyroid hormone (hPTH) has an anabolic effect on bone in animals and humans and is expected to be a potent agent for the treatment of osteoporosis. However, little is known about the effects of hPTH on cancellous bone healing after cancellous bone fractures or osteotomies. We evaluated whether hPTH enhanced bone union at the site of cancellous bone osteotomy and further elucidated the possible mechanisms of hPTH effects on cancellous bone healing. After a bilateral ovariectomy (OVX) or sham operation in mature female rats, cancellous bone osteotomy was performed on the right proximal tibia. After once-a-week administration of hPTH (1-34) (100 microg/kg) or its vehicle for 4 weeks, bilateral tibiae including osteotomy and non-osteotomy sites were harvested. Along with conventional bone histomorphometry, cancellous bone union at the osteotomy site and the rate of proliferating cells immunostained with proliferating cell nuclear antigen (PCNA) and adipocytes in the surrounding bone marrow were evaluated. hPTH increased cancellous bone volume by stimulating bone formation in both normal and OVX rats and suppressed adipocyte volume (p<0.05). The percentage of PCNA-positive cells at the osteotomy site after PTH treatment was 2- to 3-fold higher than that of vehicle treatment controls both in sham-operated and OVX rats (p<0.05). The magnitude of increase in the percentage of PCNA-positive cells after PTH treatment at the osteotomy site was two times higher than that at the non-osteotomy site. Furthermore, PTH treatment increased cancellous bone union after osteotomy both in sham-operated and OVX rats (p<0.05). These results suggest that hPTH enhances cancellous bone healing at the site of osteotomy with, at least in part, a local regulating action that increases osteoblastogenesis and decreases adipocytogenesis at and around the osteotomy. PMID:17997377

Nozaka, Koji; Miyakoshi, Naohisa; Kasukawa, Yuji; Maekawa, Shigeto; Noguchi, Hideaki; Shimada, Yoichi

2008-01-01

342

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

SciTech Connect

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

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

2006-09-01

343

Functioning oxyphil parathyroid adenoma: a case report.  

PubMed

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

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

2014-04-01

344

Utility of intraoperative bilateral internal jugular venous sampling with rapid parathyroid hormone testing in guiding patients with a negative sestamibi scan for minimally invasive parathyroidectomy—a randomized controlled trial  

Microsoft Academic Search

Background and aims  The purpose of this study was to determine the utility of bilateral internal jugular venous sampling with rapid parathyroid\\u000a hormone assay (BIJV–IOPTH) in comparison to endocrine surgeon-performed ultrasonography of the neck as an alternative localizing\\u000a modality in guiding patients with primary hyperparathyroidism (pHPT) and negative sestamibi scans for minimally invasive parathyroidectomy\\u000a (MIP).\\u000a \\u000a \\u000a \\u000a Patients and methods  Seventy eight consenting patients

Marcin Barczynski; Aleksander Konturek; Alicja Hubalewska-Dydejczyk; Stanislaw Cichon; Wojciech Nowak

2009-01-01

345

Women’s Health Initiative Clinical Trials: Interaction of calcium plus vitamin D and Hormone Therapy  

PubMed Central

Objective To test the added value of Calcium and vitamin D (CaD) for fracture prevention among women taking postmenopausal hormone therapy (HT). Methods A prospective, partial-factorial design, randomized controlled double blind trial amongst Women’s Health Initiative post-menopausal participants, ages 50–79, at 40 centers in the US, with 7.1 years average follow-up. 27,347 women were randomized to HT (conjugated estrogen 0.625 mg alone, or CEE 0.625 mg daily plus medroxyprogesterone acetate 2.5mg) and 36,282 women randomized to either 1000mg elemental calcium (carbonate) plus 400 IU of vitamin D3 daily each compared to placebo. A total of 16,089 women were in both arms. The predefined outcomes were adjudicated hip fractures and measured bone mineral density. Results Interaction between HT and CaD on hip fracture (P-interaction = 0.01) was shown. The effect of CaD was stronger among women assigned to HT (HR, 0.59; 95%CI, 0.38–0.93) than placebo (HR, 1.20; 95%CI, 0.85, 1.69). The effect of HT on hip fracture was stronger among women assigned to active CaD (HR, 0.43; 0.28–0.66) than placebo (HR, 0.87; 95%CI, 0.60–1.26). CaD supplementation enhanced the anti-fracture effect of the HT at all levels of personal calcium intake. There was no interaction of HT and CaD on change in hip or spine BMD. Conclusions Postmenopausal women at normal risk of hip fracture on HT, supplementation with CaD significantly reduced incident hip fracture beyond HT alone; at all levels of personal baseline total calcium intake. PMID:23799356

Robbins, John A; Aragaki, Aaron; Crandall, Carolyn J; Manson, Joann E; Carbone, Laura; Jackson, Rebecca; Lewis, Cora E.; Johnson, Karen C.; Sarto, Gloria; Stefanick, Marcia L; Wactawski-Wende, Jean

2013-01-01

346

Effects on thyroid hormone metabolism and depletion of lung vitamin A in rats by airborne particulate matter  

SciTech Connect

Thyroxine (T4) and vitamin A are important regulators of normal epithelial differentiation and proliferation and might act in the promotion phase of carcinogenesis. Thyroid hormone and vitamin A metabolism are linked by a common plasma carrier protein, transthyretin (TTR). Polychlorinated biphenyls (PCBs) and related organochlorine compounds deplete vitamin A and thyroxine by interaction with TTR and alteration of their metabolism in hepatic and other organs. In the present report an outdoor airborne particulate matter (APM) extract was tested for both interaction with thyroid hormone and vitamin A metabolism, in order to address the question of whether APM has the potency to deplete vitamin A and thyroid hormones. Furthermore, studies were performed to characterize compounds present in APM that interact with TTR. A third aim was to compare the interaction of APM extracts with TTR and thyroxine-binding globulin (TBG), the major carrier protein for thyroxine in humans. Results showed that a single treatment of rats with an outdoor APM extract depleted plasma thyroxine and triiodothyronine levels and increased plasma retinol levels gradually over the time period studied, while liver retinol, lung retinol, and retinyl palmitate levels were depleted by 30-50%. As outdoor APM was able to inhibit T4-TTR binding in vitro, this suggests that the reduction in thyroxine levels in vivo is caused by the same phenomenon. Experiments showed that the neutral fraction of the APM extract accounted for most of the inhibitory activity on T4-TTR binding. Polycyclic aromatic hydrocarbons and nitrated derivatives are not likely to be responsible for the activity of the neutral fraction, because several representatives of these compounds showed no or very little interaction with TTR. Pentachlorophenol, a compound with known inhibitory activity on T4-TTR binding, was detected in the organic acid fraction of both a cigarette smoke sample and an outdoor APM sample.

Heussen, G.A.; Schefferlie, G.J.; Talsma, M.J.; van Til, H.; Dohmen, M.J.; Brouwer, A.; Alink, G.M. (Agricultural Univ., Wageningen (Netherlands))

1993-04-01

347

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

NASA Technical Reports Server (NTRS)

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

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

1998-01-01

348

Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers.  

PubMed

Osteoporosis in men poses a unique therapeutic challenge. Clinical studies have focused largely on the more prevalent problem of post-menopausal osteoporosis, with few gender-specific studies exploring treatment options in men. Idiopathic osteoporosis in middle-aged men presents an additional dilemma, because in the majority of patients it is a low bone turnover state for which there are currently no available anabolic agents. We conducted an 18-month randomized, double blind, placebo-controlled trial of 23 men with idiopathic osteoporosis, 30-68 yr old (mean age +/- SEM, 50 +/- 1.9 yr). All patients received 1,500 mg calcium and 400 IU vitamin D daily. Ten patients were randomized to receive 400 IU PTH-(1-34), and 13 patients received vehicle, administered by daily sc injection. Serum and urinary biochemistries, including markers of bone turnover were measured every 3 months. Bone densitometry of the lumbar spine, hip, and radius was performed every 6 months. PTH-(1-34) was associated with a marked 13.5% increase in bone mass at the lumbar spine, whereas that in the control group did not change (P < 0.001). The mean lumbar spine T-score improved from -3.5 +/- 0.2 to 2.4 +/- 0.4. Femoral neck bone mineral density in the PTH-treated group increased 2.9% (P < 0.05). The 1/3 site of the distal radius showed no change from baseline in the PTH-treated group. There were no significant changes in serum calcium concentration, 24-h urinary calcium excretion, or 1,25-dihydroxyvitamin D in either group. All markers of bone turnover increased in the PTH-treated patients, with the greatest changes in serum osteocalcin and urinary N-telopeptide (230% and 375% above baseline by 12 months, respectively; P < 0.001). Free pyridinoline and markers of bone formation that showed little correlation with each other at baseline, became highly correlated in the PTH-treated group (r = 0.1; P = 0.29 at baseline; to r = 0.7; P < 0.0001 at 18 months), a pattern absent in the control patients. The best predictor of the lumbar spine response to PTH at 18 months was the combination of pyridinoline at baseline and osteocalcin at 3 months (70% of the variance). PTH is a potent stimulator of skeletal dynamics in men with idiopathic, low turnover osteoporosis; is associated with substantial increases in lumbar spine and hip bone density; and may prove to be an efficacious anabolic agent in men with this disorder. PMID:10999788

Kurland, E S; Cosman, F; McMahon, D J; Rosen, C J; Lindsay, R; Bilezikian, J P

2000-09-01

349

Adolescent Girls in Maine Are at Risk for Vitamin D Insufficiency  

Microsoft Academic Search

The objective was to determine the seasonal fluctuations in serum 25-hydroxyvitamin D (25-OHD) in a group of healthy adolescents living in a northern climate. Twenty- three 9- to 11-year-old girls participated in the study from September 2000 to March 2003. Serum 25-OHD and parathyroid hormone levels were measured each Septem- ber and March. Dietary intake of vitamin D was assessed

SUSAN S. SULLIVAN; CLIFFORD J. ROSEN; WILLIAM A. HALTEMAN; TAI C. CHEN; MICHAEL F. HOLICK

350

Nitric oxide synthase in human parathyroid glands and parathyroid adenomas  

Microsoft Academic Search

Nitric oxide (NO) is a novel gaseous intercellular transmitter thought to play important physiological roles in the regulation\\u000a of blood flow and hormone secretion in, for example, the pituitary, the thyroid, and the endocrine pancreas. Whether nitric\\u000a oxide synthase (NOS) is present in the human parathyroid glands has not yet been demonstrated. In the present study, histologically\\u000a normal, but functionally

Lena Luts; Anders Bergenfelz; Jan Alumets; Frank Sundler

1996-01-01

351

[Vitamin D and kidney diseases].  

PubMed

Calcitriol and analogs inhibit renin-angiotensin system, which has a pivotal role in glomerular and tubulo-interstitial damages and proteinuria, and inhibit NF-?B activation which is known to play an important role in renal diseases by promoting inflammation and fibrogenesis. Vitamin D presents interesting pleiotropic effects for the CKD patient (reduction of mortality, antiproteinuric effect and anti-inflammatory properties). "Native" vitamin D (cholecalciferol or ergocalciferol) administration in these patients also decrease parathyroid hormone levels. Native vitamin D administration in CKD patients is safe and does not lead to increased risk of vascular calcification, despite the known hypercalcemic and hyperphosphoremic properties of the molecule in its active form. Native vitamin D administration is not associated with an increased risk of renal stones, at pharmacological doses and without important concomitant administration of calcium salts. In the field of renal transplantation, experimental studies show that vitamin D analogs have a protective role against acute rejection but clinical studies remain mainly observational. PMID:24055557

Cavalier, Étienne; Thervet, Éric; Courbebaisse, Marie

2013-10-01

352

Recombinant human parathyroid hormone (PTH 1-34) and low-intensity pulsed ultrasound have contrasting additive effects during fracture healing.  

PubMed

Fracture healing is thought to be naturally optimized; however, recent evidence indicates that it may be manipulated to occur at a faster rate. This has implications for the duration of morbidity associated with bone injuries. Two interventions found to accelerate fracture healing processes are recombinant human parathyroid hormone [1-34] (PTH) and low-intensity pulsed ultrasound (LIPUS). This study aimed to investigate the individual and combined effects of PTH and LIPUS on fracture healing. Bilateral midshaft femur fractures were created in Sprague-Dawley rats, and the animals treated 7 days/week with PTH (10 microg/kg) or a vehicle solution. Each animal also had one fracture treated for 20 min/day with active-LIPUS (spatial-averaged, temporal-averaged intensity [I(SATA)]=100 mW/cm(2)) and the contralateral fracture treated with inactive-LIPUS (placebo). Femurs were harvested 35 days following injury to permit micro-computed tomography, mechanical property and histological assessments of the fracture calluses. There were no interactions between PTH and LIPUS indicating that their effects were additive rather than synergistic. These additive effects were contrasting with LIPUS primarily increasing total callus volume (TV) without influencing bone mineral content (BMC), and PTH having the opposite effect of increasing BMC without influencing TV. As a consequence of the effect of LIPUS on TV but not BMC, it decreased volumetric bone mineral density (vBMD) resulting in a less mature callus. The decreased maturity and persistence of cartilage at the fracture site when harvested offset any beneficial mechanical effects of the increased callus size with LIPUS. In contrast, the effect of PTH on callus BMC but not TV resulted in increased callus vBMD and a more mature callus. This resulted in PTH increasing fracture site mechanical strength and stiffness. These data suggest that PTH may have utility in the treatment of acute bone fractures, whereas LIPUS at an I(SATA) of 100 mW/cm(2) does not appear to be indicated in the management of closed, diaphyseal fractures. PMID:19071238

Warden, Stuart J; Komatsu, David E; Rydberg, Johanna; Bond, Julie L; Hassett, Sean M

2009-03-01

353

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

PubMed Central

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

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

354

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

PubMed Central

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

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

2014-01-01

355

Prevalence of vitamin D insufficiency among healthy school-age Cree children  

PubMed Central

BACKGROUND: First Nations children are at higher risk for vitamin D deficiency and rickets. OBJECTIVE: To assess the prevalence of vitamin D deficiency and the correlations between fat mass, parathyroid hormone and dietary habits with serum vitamin D level in a random sample of Cree children eight to 14 years of age. METHODS: Serum 25-hydroxyvitamin D (25[OH]D) levels and additional information regarding anthropometrics and dietary habits were obtained from participants in two Cree communities. Vitamin D deficiency and insufficiency was defined as serum 25(OH)D levels <30 nmol/L and <50 nmol/L, respectively. Proportions to estimate the vitamin D status were weighted to account for the complex sampling design, and Pearson’s correlation coefficients were used to estimate the associations of milk and fish intake, parathyroid hormone and fat mass with serum 25(OH)D levels. RESULTS: Data from 52 healthy Cree children (mean [± SD] age 11.1±2.0 years; 27 boys) were included in the analyses. The median serum 25(OH)D level was 52.4 nmol/L (range 22.1 nmol/L to 102.7 nmol/L). Forty-three percent (95% CI 29% to 58%) and 81% (95% CI 70% to 92%) of Cree children had vitamin D levels <50 nmol/L and <75 nmol/L, respectively. Vitamin D intake was positively associated with serum 25(OH)D levels. Obese children had lower vitamin D levels; however, the difference was nonsignificant. CONCLUSION: There may be a substantial proportion of Cree children who are vitamin D deficient. Increasing age, lower dietary vitamin D intake and, possibly, higher body mass index were associated with decreased vitamin D levels; however, causality cannot be inferred. PMID:24665228

Riverin, Bruno; Dewailly, Eric; Côté, Suzanne; Johnson-Down, Louise; Morin, Suzanne; Dodin, Sylvie

2014-01-01

356

Vitamin D physiology.  

PubMed

Vitamin D3 is synthesized in the skin during summer under the influence of ultraviolet light of the sun, or it is obtained from food, especially fatty fish. After hydroxylation in the liver into 25-hydroxyvitamin D (25(OH)D) and kidney into 1,25-dihydroxyvitamin D (1,25(OH)2D), the active metabolite can enter the cell, bind to the vitamin D-receptor and subsequently to a responsive gene such as that of calcium binding protein. After transcription and translation the protein is formed, e.g. osteocalcin or calcium binding protein. The calcium binding protein mediates calcium absorption from the gut. The production of 1,25(OH)2D is stimulated by parathyroid hormone (PTH) and decreased by calcium. Risk factors for vitamin D deficiency are premature birth, skin pigmentation, low sunshine exposure, obesity, malabsorption and advanced age. Risk groups are immigrants and the elderly. Vitamin D status is dependent upon sunshine exposure but within Europe, serum 25(OH)D levels are higher in Northern than in Southern European countries. Severe vitamin D deficiency causes rickets or osteomalacia, where the new bone, the osteoid, is not mineralized. Less severe vitamin D deficiency causes an increase of serum PTH leading to bone resorption, osteoporosis and fractures. A negative relationship exists between serum 25(OH)D and serum PTH. The threshold of serum 25(OH)D, where serum PTH starts to rise is about 75nmol/l according to most surveys. Vitamin D supplementation to vitamin D-deficient elderly suppresses serum PTH, increases bone mineral density and may decrease fracture incidence especially in nursing home residents. The effects of 1,25(OH)2D and the vitamin D receptor have been investigated in patients with genetic defects of vitamin D metabolism and in knock-out mouse models. These experiments have demonstrated that for active calcium absorption, longitudinal bone growth and the activity of osteoblasts and osteoclasts both 1,25(OH)2D and the vitamin D receptor are essential. On the other side, bone mineralization can occur by high ambient calcium concentration, so by high doses of oral calcium or calcium infusion. The active metabolite 1,25(OH)2D has its effects through the vitamin D receptor leading to gene expression, e.g. the calcium binding protein or osteocalcin or through a plasma membrane receptor and second messengers such as cyclic AMP. The latter responses are very rapid and include the effects on the pancreas, vascular smooth muscle and monocytes. Muscle cells contain vitamin D receptor and several studies have demonstrated that serum 25(OH)D is related to physical performance. The active metabolite 1,25(OH)2D has an antiproliferative effect and downregulates inflammatory markers. Extrarenal synthesis of 1,25(OH)2D occurs under the influence of cytokines and is important for the paracrine regulation of cell differentiation and function. This may explain that vitamin D deficiency can play a role in the pathogenesis of auto-immune diseases such as multiple sclerosis and diabetes type 1, and cancer. In conclusion, the active metabolite 1,25(OH)2D has pleiotropic effects through the vitamin D receptor and vitamin D responsive elements of many genes and on the other side rapid non-genomic effects through a membrane receptor and second messengers. Active calcium absorption from the gut depends on adequate formation of 1,25(OH)2D and an intact vitamin D receptor. Bone mineralization mainly depends on ambient calcium concentration. Vitamin D metabolites may play a role in the prevention of auto-immune disease and cancer. PMID:16563471

Lips, P

2006-09-01

357

Cellular physiology and pathophysiology of the parathyroid glands  

Microsoft Academic Search

This report provides insight into parathyroid gland physiology and the pathophysiology of hyperparathyroidism (HPT). Increases in the extracellular calcium concentration constitute the primary physiological signal for inhibition of parathyroid hormone (PTH) release. Transduction of the external signal into a cellular response involves activation of a cation receptor mechanism on the plasma membrane with rapid rise in the cytoplasmic calcium concentration

Göran Åkerström; Jonas Rastad; Sverker Ljunghall; Peter Ridefelt; Claes Juhlin; Erik Gylfe

1991-01-01

358

Regulation of PTH-related protein gene expression by vitamin D in PC3 prostate cancer cells  

Microsoft Academic Search

Parathyroid hormone-related protein (PTHrP) is expressed by prostate cancer cells. Since PTHrP increases prostate cancer cell growth and enhances the osteolytic effects of prostate cancer cells, it is important to control PTHrP expression in prostate cancer. Vitamin D exerts a protective effect against prostate cancer through its antiproliferative actions. We investigated whether this steroid also downregulates PTHrP gene transcription, using

Veronica A. Tovar Sepulveda; Miriam Falzon

2002-01-01

359

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

Microsoft Academic Search

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

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

1999-01-01

360

Vitamin D, chronic kidney disease and survival: a pluripotent hormone or just another bone drug?  

Microsoft Academic Search

It is now about 40 years ago that the mechanism of renal 1-?-hydroxylation of vitamin D was discovered and characterized.\\u000a After this seminal observation, the key role of the active vitamin D derivative 1, 25-(OH)2-vitamin D (calcitriol) in calcium\\u000a homeostasis and bone mineralization, and its specific role in the course of chronic kidney disease (CKD) and renal osteopathy,\\u000a was unraveled step

Patrick H. Biggar; Orfeas Liangos; Holger Fey; Vincent M. Brandenburg; Markus Ketteler

2011-01-01

361

Short-term, high-dose parathyroid hormone-related protein as a skeletal anabolic agent for the treatment of postmenopausal osteoporosis.  

PubMed

PTH-related protein (PTHrP) is homologous with PTH. PTH, an effective anabolic agent for treating osteoporosis, has been shown to stimulate both bone resorption by osteoclasts and bone formation by osteoblasts. We examined whether PTHrP might share anabolic properties in osteoporosis. A 3-month double-blind, prospective, placebo-controlled, randomized clinical trial was performed in 16 healthy postmenopausal women with osteoporosis. All received calcium and vitamin D, and all continued their prior hormone replacement therapy. One group also received daily sc PTHrP (6.56 microg/kg x d, or approximately 400 microg/d), and the other group received placebo injections. The PTHrP group displayed a 4.7% increase in lumbar spine bone mineral density (BMD) and also demonstrated an increase in osteoblastic bone formation, as assessed using serum osteocalcin measurements. In contrast, there was no increase in bone-specific alkaline phosphatase and collagen-1 propeptide or either of two markers of osteoclastic bone resorption, N-telopeptide, or deoxypyridinoline. One subject in the placebo group withdrew from the study, but there were no significant adverse events in the PTHrP group. PTHrP administered sc in high doses for only 3 months appears to be a potent anabolic agent, producing a 4.7% increase in lumbar spine BMD. This compares very favorably to available antiresorptive drugs for osteoporosis and is similar to the increases in BMD at this early time point reported for PTH. Despite the high doses, PTHrP was well tolerated. Larger clinical trials are required to confirm these results and fully assess the anabolic potential of PTHrP in osteoporosis. PMID:12574182

Horwitz, Mara J; Tedesco, Mary Beth; Gundberg, Caren; Garcia-Ocana, Adolfo; Stewart, Andrew F

2003-02-01

362

Phosphate metabolism and vitamin D  

PubMed Central

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

Fukumoto, Seiji

2014-01-01

363

Human Parathyroid Hormone IMMUNOLOGICAL CHARACTERIZATION OF ANTIBODIES AGAINST A GLANDULAR EXTRACT AND THE SYNTHETIC AMINO-TERMINAL FRAGMENTS 1-12 AND 1-34 AND THEIR USE IN THE DETERMINATION OF IMMUNOREACTIVE HORMONE IN HUMAN SERA  

PubMed Central

Antibodies to a urea-trichloroacetic acid extract [hPTH-(TCA)] of human parathyroid tumors and to the synthetic NH2-terminal fragments of human parathyroid hormone hPTH-(1-12) and -(1-34) were developed in goats to characterize immunochemically various PTH preparations and to estimate immunoreactive PTH (iPTH) in human sera. They were quantitated on the basis of their capacity to bind [131I]-hPTH-(1-12), [131I]hPTH-(1-34) or [131I]bovine PTH (bPTH-(1-84)). The quality of the antibodies was assessed by reference to inhibition of their interaction with labeled peptides by synthetic hPTH comprising 34 NH2-terminal amino acid residues or fragments thereof [hPTH-(1-12), -(13-34), -(18-34), -(25-34), -(18-24)] or by the Sephadex G-100-purified full-length peptide hPTH-(1-84) [hPTH-(1-84)G-100]. The synthetic peptides used in this work correspond in their structure to the NH2-terminal amino acid sequence 1-34, as elucidated by Brewer and collaborators (1972. Proc. Natl. Acad. Sci. U. S. A.69: 3583-3588). Inhibition studies were also carried out with bPTH-(1-34) and bPTH-(1-84). Anti-hPTH-(TCA) exhibited specificities directed to determinants in the COOH-terminal and NH2-terminal part of hPTH-(1-84) and exhibited cross-reactivity with bPTH-(1-84). Anti-hPTH-(1-34), on the other hand, showed immunological specificities mainly directed to antigenic determinants located in the COOH-terminal half of hPTH-(1-34). In addition, some reactivity with the NH2-terminal hPTH-(1-12) and with the extractive full-length peptides of human and bovine origin was observed. Antibodies to hPTH-(1-12) cross-reacted with hPTH-(1-34) and -(1-84)G-100. iPTH was radioimmunologically determined in human sera by the following systems: (a) [131I]bPTH-(1-84), anti-hPTH-(TCA) and hPTH-(1-84)G-100 as standard; (b) [131I]hPTH-(1-34), anti-hPTH-(1-34) and hPTH-(1-34) as standard. With system (a), COOH-terminal fragments of hPTH-(1-84) having a molecular weight of approximately 7,000 were detected, and there was an almost total discrimination of serum iPTH levels in normal and in hyperparathyroid subjects. With system (b), on the other hand, several molecular species of iPTH were detected, including a component larger than hPTH-(1-84) and others similar to hPTH-(1-84) and to a fragment co-eluting with the NH2-terminal fragment hPTH-(1-34). When serum iPTH was assayed in system (b), there was a large overlap of iPTH levels in control subjects and in patients with primary hyperparathyroidism. PMID:4474187

Fischer, Jan A.; Binswanger, Ulrich; Dietrich, Felix M.

1974-01-01

364

Effects of Vitamin A Deficiency and Retinoic Acid Treatment on Expression of a Phosphoenolpyruvate Carboxykinase-Bovine Growth Hormone Gene in Transgenic Mice  

Microsoft Academic Search

Vitamin A regulation of specific promoter domains of the phosphoenolpyruvate carboxykinase (PEPCK) gene was tested in a PEPCK\\/bovine growth hormone (bGH) transgenic mouse model. Vitamin A deficiency causes a significant decrease in hepatic bGH mRNA when expression is driven by either a 533-base-pair (bp) PEPCK promoter fragment (from position ?460 to +73) or a 428-bp PEPCK promoter fragment (from position

D. J. Shin; A. Y. Tao; M. M. Mcgrane

1995-01-01

365

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

PubMed Central

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

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

2007-01-01

366

Life-threatening intrathyroidal parathyroid adenoma  

PubMed Central

Acute primary hyperparathyroidism and parathyroid crisis are characterized by life-threatening hypercalcemia, a rare disorder. A 69-year-old female patient presented at our hospital’s neurology clinic with weakness, nausea, vomiting, depression, and hypercalcemia. Treatment of hypercalcemia resulted in no improvement in neurological symptoms, indicating resistance to treatment. Thyroid ultrasonography and parathyroid scintigraphy revealed hypoechoic nodules in the right lobe, pieces of nodules in the left lobe, and high serum calcium and parathyroid hormone levels. After provision of intensive medical treatment including hydration, diuresis, and bisphosphonate infusion resulted in only minimal decrease in the calcium level, urgent surgical treatment was performed. Frozen biopsy of the right intrathyroidal giant parathyroid adenoma in the right lobe confirmed initial diagnosis of primary hyperparathyroidism. Based on the biopsy findings, right parathyroidectomy and right total and left subtotal thyroidectomy were performed. Histopathologic examination revealed a parathyroid adenoma localized inside large thyroid nodules. Review of the findings resulted in diagnosis of intrathyroidal parathyroid adenoma. Symptoms of hypercalcemia improved rapidly during the postoperative period. PMID:25785164

Dogan, Ugur; Koc, Umit; Mayir, Burhan; Habibi, Mani; Dogan, Berna; Gomceli, Ismail; Bulbuller, Nurullah

2015-01-01

367

Problems in early diagnosis of bladder cancer in a spinal cord injury patient: Report of a case of simultaneous production of granulocyte colony stimulating factor and parathyroid hormone-related protein by squamous cell carcinoma of urinary bladder  

PubMed Central

Background Typical symptoms and signs of a clinical condition may be absent in spinal cord injury (SCI) patients. Case presentation A male with paraplegia was passing urine through penile sheath for 35 years, when he developed urinary infections. There was no history of haematuria. Intravenous urography showed bilateral hydronephrosis. The significance of abnormal outline of bladder was not appreciated. As there was large residual urine, he was advised intermittent catheterisation. Serum urea: 3.5 mmol/L; creatinine: 77 umol/L. A year later, serum urea: 36.8 mmol/l; creatinine: 632 umol/l; white cell count: 22.2; neutrophils: 18.88. Ultrasound: bilateral hydronephrosis. Bilateral nephrostomy was performed. Subsequently, blood tests showed: Urea: 14.2 mmol/l; Creatinine: 251 umol/l; Adjusted Calcium: 3.28 mmol/l; Parathyroid hormone: < 0.7 pmol/l (1.1 – 6.9); Parathyroid hormone-related protein (PTHrP): 2.3 pmol/l (0.7 – 1.8). Ultrasound scan of urinary bladder showed mixed echogenicity, which was diagnosed as debris. CT of pelvis was interpreted as vesical abscess. Urine cytology: Transitional cells showing mild atypia. Bladder biopsy: Inflamed mucosa lined by normal urothelial cells. A repeat ultrasound scan demonstrated a tumour arising from right lateral wall; biopsy revealed squamous cell carcinoma. In view of persistently high white cell count and high calcium level, immunohistochemistry for G-CSF and PTHrP was performed. Dense staining of tumour cells for G-CSF and faintly positive staining for C-terminal PTHrP were observed. This patient expired about five months later. Conclusion This case demonstrates how delay in diagnosis of bladder cancer could occur in a SCI patient due to absence of characteristic symptoms and signs. PMID:12201902

Vaidyanathan, Subramanian; Mansour, Paul; Ueno, Munehisa; Yamazaki, Kazuto; Wadhwa, Meenu; Soni, Bakul M; Singh, Gurpreet; Hughes, Peter L; Watson, Ian D; Sett, Pradipkumar

2002-01-01

368

Effect of angiotensin II type 1 receptor blocker on renal function, arterial blood pressure and parathyroid hormone related protein over expression in cadmium induced nephrotoxicity in adult male rats  

PubMed Central

Objective: To study the possible effect of angiotensin II type 1 Receptor blocker (AT1 blocker) on renal function, arterial blood pressure and parathyroid hormone related protein over expression in cadmium induced nephrotoxicity in adult male rats. Forty five rats were divided randomly into a control (group I), group II, received cadmium chloride at a dose of 5 mg/kg/day, orally, for nine weeks, group III received telmisartan (TEL) treatment (1 mg/kg/day, orally) one week before cadmium administration and continued for ten weeks. Results: Telmisartan significantly reduced blood urea nitrogen (BUN) and serum creatinine levels which were increased significantly by cadmium. Telmisartan significantly suppressed lipid peroxidation, compensated deficits in the antioxidant defenses (super oxide dismutase (SOD) level and catalase activity), decreased the elevations of nitric oxide (NO) and cadmium ion concentrations in renal tissue observed in Cd-treated rats. Group III had a significant decrease of urinary levels of total protein, N-acetyl-?-d-glucosaminidase (NAG), alkaline phosphatase (ALP) and ?-glutamyl-transpeptidase (GGT) and urinary 8-isoprostanes than those of group II. Telmisartan decreased the systolic blood pressure significantly than those of group II. Histopathological examination revealed that cadmium-induced renal tissue damage was ameliorated by telmisartan treatment. Immunohistochemical analysis revealed that telmisartan significantly decreased the cadmium-induced overexpression of parathyroid hormone receptor 1 (PTHR1) in renal tissue. RT-PCR analysis showed that Cd increased renal expression of PTHrP; however telmisartan could decrease the expression of PTHrP in group III. Conclusion: Blocking AT1 receptors significantly decreases PTHrP over expression and ameliorates renal dysfunction in Cd induced nephrotoxicity. These data suggest that Ang II might contribute to pathophysiology and deleterious effects in cadmium nephrotoxicity. PMID:23750309

Ahmed, Marwa A

2013-01-01

369

Dietary contaminant exposure affects plasma testosterone, but not thyroid hormones, vitamin A, and vitamin E, in male juvenile arctic foxes (Vulpes lagopus).  

PubMed

Levels of persistent organic pollutants (POP), such as polychlorinated biphenyls (PCB), are high in many Arctic top predators, including the Arctic fox (Vulpes lagopus). The aim of this study was to examine possible endocrine-disruptive effects of dietary POP exposure in male juvenile Arctic foxes in a controlled exposure experiment. The study was conducted using domesticated farmed blue foxes (Vulpes lagopus) as a model species. Two groups of newly weaned male foxes received a diet supplemented with either minke whale (Baleneoptera acutorostrata) blubber that was naturally contaminated with POP (exposed group, n?=?5 or 21), or pork (Sus scrofa) fat (control group, n?=?5 or 21). When the foxes were 6 mo old and had received the 2 diets for approximately 4 mo (147 d), effects of the dietary exposure to POP on plasma concentrations of testosterone (T), thyroid hormones (TH), thyroid-stimulating hormone (TSH), retinol (vitamin A), and tocopherol (viramin E) were examined. At sampling, the total body concentrations of 104 PCB congeners were 0.1 ± 0.03 ?g/g lipid weight (l.w.; n?=?5 [mean ± standard deviation]) and 1.5 ± 0.17 ?g/g l.w. (n?=?5) in the control and exposed groups, respectively. Plasma testosterone concentrations in the exposed male foxes were significantly lower than in the control males, being approximately 25% of that in the exposed foxes. There were no between-treatment differences for TH, TSH, retinol, or tocopherol. The results suggest that the high POP levels experienced by costal populations of Arctic foxes, such as in Svalbard and Iceland, may result in delayed masculine maturation during adolescence. Sex hormone disruption during puberty may thus have lifetime consequences on all aspects of reproductive function in adult male foxes. PMID:23030655

Hallanger, Ingeborg G; Jørgensen, Even H; Fuglei, Eva; Ahlstrøm, Øystein; Muir, Derek C G; Jenssen, Bjørn Munro

2012-01-01

370

Vitamin D Deficiency and Exogenous Vitamin D Excess Similarly Increase Diffuse Atherosclerotic Calcification in Apolipoprotein E Knockout Mice  

PubMed Central

Background Observational data associate lower levels of serum vitamin D with coronary artery calcification, cardiovascular events and mortality. However, there is little interventional evidence demonstrating that moderate vitamin D deficiency plays a causative role in cardiovascular disease. This study examined the cardiovascular effects of dietary vitamin D deficiency and of vitamin D receptor agonist (paricalcitol) administration in apolipoprotein E knockout mice. Methods Mice were fed atherogenic diets with normal vitamin D content (1.5IU/kg) or without vitamin D. Paricalcitol, or matched vehicle, was administered 3× weekly by intraperitoneal injection. Following 20 weeks of these interventions cardiovascular phenotype was characterized by histological assessment of aortic sinus atheroma, soluble markers, blood pressure and echocardiography. To place the cardiovascular assessments in the context of intervention effects on bone, structural changes at the tibia were assessed by microtomography. Results Vitamin D deficient diet induced significant reductions in plasma vitamin D (p<0.001), trabecular bone volume (p<0.01) and bone mineral density (p<0.005). These changes were accompanied by an increase in calcification density (number of calcifications per mm2) of von Kossa-stained aortic sinus atheroma (461 versus 200, p<0.01). Paricalcitol administration suppressed parathyroid hormone (p<0.001), elevated plasma calcium phosphate product (p<0.005) and induced an increase in calcification density (472 versus 200, p<0.005) similar to that seen with vitamin D deficiency. Atheroma burden, blood pressure, metabolic profile and measures of left ventricular hypertrophy were unaffected by the interventions. Conclusion Vitamin D deficiency, as well as excess, increases atherosclerotic calcification. This phenotype is induced before other measures of cardiovascular pathology associated clinically with vitamin D deficiency. Thus, maintenance of an optimal range of vitamin D signalling may be important for prevention of atherosclerotic calcification. PMID:24586387

Ellam, Timothy; Hameed, Abdul; ul Haque, Risat; Muthana, Munitta; Wilkie, Martin; Francis, Sheila E.; Chico, Timothy J. A.

2014-01-01

371

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

PubMed

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

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

2013-09-01

372

The role of vitamin D in the medullary bone formation in egg-laying Japanese quail and in immature male chicks treated with sex hormones.  

PubMed

The effect of vitamin D3 on medullary bone formation was investigated in egg-laying Japanese quail and in immature male chicks treated with sex hormones. When laying quail were fed a vitamin D-deficient diet for 16 days, their eggshell weights and egg production rate were markedly reduced in a time-dependent manner with a significant decrease in plasma calcium and 25-hydroxyvitamin D3 levels. The calcium content of the medullary bone of femurs decreased markedly with the progress of vitamin D deficiency, whereas that of the cortical bone remained unchanged. Quantitative histological examination also showed that the area of the mineralized portion of medullary bone in quail that were fed the vitamin D-deficient diet markedly decreased compared with that in the control laying quail, whereas the total area of the mineralized and unmineralized portions of medullary bone in the bone marrow cavity increased moderately. Daily administration of vitamin D3 (0.75 microgram/day) to the vitamin D-deficient quail increased the mineralization of medullary bone as early as day 4. Daily administration of both estradiol (0.3 mg/day) and testosterone (0.9 mg/day) for 3 weeks to immature male chicks induced an apparent hypercalcemia and matrix formation of medullary bone, regardless of the vitamin D status of the chicks. Mineralization of medullary bone was observed only when vitamin D3 was administered together with the sex hormones. These results suggest that vitamin D3 is directly involved in the mineralization of medullary bone in birds. PMID:6311373

Takahashi, N; Shinki, T; Abe, E; Horiuchi, N; Yamaguchi, A; Yoshiki, S; Suda, T

1983-07-01

373

PTH secretion of “manipulated” parathyroid adenomas  

Microsoft Academic Search

Purpose  Increased secretion of parathyroid hormone (PTH) and its fragments intraoperatively may influence PTH monitoring. The purpose\\u000a of this study was to investigate whether “intended intraoperative manipulation” of parathyroid adenomas through mechanical\\u000a stimulation (through squeezing or manual rubbing) would lead to increased PTH excretion. The different PTH fragments that\\u000a result from this kind of manipulation were correlated and analyzed.\\u000a \\u000a \\u000a \\u000a Methods  The enlarged

Philipp Riss; Reza Asari; Christian Scheuba; Christian Bieglmayer; Bruno Niederle

2009-01-01

374

Prevention of Femoral and Lumbar Bone Loss with Hormone Replacement Therapy and Vitamin D3 in Early Postmenopausal Women: A Population-Based 5Year Randomized Trial  

Microsoft Academic Search

The long term effects of hormone replacement therapy (HRT) and vitamin D3 (Vit D) on bone mineral density (BMD) were studied. A total of 464 nonosteoporotic early postmenopausal women from the Kuopio Osteoporosis Study (n 5 13100) were randomized to four groups: 1) HRT (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate, 2) Vit D3 (300

MARJA KOMULAINEN; HEIKKI KROGER; MARJO T. TUPPURAINEN; ANNA-MARI HEIKKINEN; ESKO ALHAVA; RISTO HONKANEN; JUKKA JURVELIN

375

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

PubMed Central

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.

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

2015-01-01

376

Parathyroid function in chronic kidney disease: role of FGF23-Klotho axis.  

PubMed

The parathyroid gland plays a central role in the regulation of mineral metabolism. In patients with chronic kidney disease (CKD), circulating levels of parathyroid hormone (PTH) are progressively increased as kidney function declines, as a result of phosphate retention, hypocalcemia, decreased production of 1,25-dihydroxyvitamin D [1,25(OH)2D], endogenous changes within the parathyroid gland, and skeletal resistance to the actions of PTH. In addition, the identification of fibroblast growth factor 23 (FGF23) and its cofactor Klotho offers important implications for the deeper understanding of disordered mineral metabolism in CKD. In early CKD, increased FGF23 to maintain neutral phosphate balance results in suppression of renal 1,25(OH)2D production and thereby triggers the early development of secondary hyperparathyroidism. FGF23 also acts directly on the parathyroid to decrease PTH synthesis and secretion, but this effect is blunted in advanced stages of CKD, due to decreased expression of the Klotho-FGF receptor 1 complex and increased concentrations of C-terminal FGF23 that competes with full-length FGF23 for binding to the receptor complex. Recent clinical studies also reported that high levels of FGF23 are associated with morbidity and mortality as well as treatment resistance to active vitamin D, suggesting the potential of FGF23 as a novel biomarker to guide treatment of disordered phosphate metabolism in CKD. This review will discuss the pathogenesis of secondary hyperparathyroidism, particularly focusing on the emerging role of the FGF23-Klotho axis in patients with CKD. PMID:23652554

Koizumi, Masahiro; Komaba, Hirotaka; Fukagawa, Masafumi

2013-01-01

377

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

PubMed Central

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

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

2014-01-01

378

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

PubMed Central

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

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

2010-01-01

379

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

PubMed

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

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

2015-01-01

380

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

PubMed Central

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

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

2015-01-01

381

Prevalence and Prognostic Implications of Vitamin D Deficiency in Chronic Kidney Disease  

PubMed Central

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.

Obi, Yoshitsugu; Hamano, Takayuki; Isaka, Yoshitaka

2015-01-01

382

Vitamin D3: a helpful immuno-modulator  

PubMed Central

The active metabolite of vitamin D, 1?, 25-dihydroxyvitamin D3 [1,25(OH)2D3], is involved in calcium and phosphate metabolism and exerts a large number of biological effects. Vitamin D3 inhibits parathyroid hormone secretion, adaptive immunity and cell proliferation, and at the same time promotes insulin secretion, innate immunity and stimulates cellular differentiation. The role of vitamin D3 in immunoregulation has led to the concept of a dual function as both as an important secosteroid hormone for the regulation of body calcium homeostasis and as an essential organic compound that has been shown to have a crucial effect on the immune responses. Altered levels of vitamin D3 have been associated, by recent observational studies, with a higher susceptibility of immune-mediated disorders and inflammatory diseases. This review reports the new developments with specific reference to the metabolic and signalling mechanisms associated with the complex immune-regulatory effects of vitamin D3 on immune cells. PMID:21896008

Di Rosa, Michelino; Malaguarnera, Michele; Nicoletti, Ferdinando; Malaguarnera, Lucia

2011-01-01

383

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

Microsoft Academic Search

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

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

1993-01-01

384

A role for magnesium in neonatal parathyroid gland function  

Microsoft Academic Search

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),

J. L. Loughead; F. Mimouni; R. C. Tsang; J. C. Khoury

1991-01-01

385

Prevalence and risk factors of vitamin D deficiency in inherited ichthyosis: A French prospective observational study performed in a reference center  

PubMed Central

Background To date, few studies have investigated serum vitamin D status in patients with inherited ichthyosis. The aim of this study was to determine the prevalence of vitamin D deficiency (defined as serum level <10 ng/mL) in a French cohort of patients and to identify associated risk factors. Methods This was a prospective observational study performed in a hospital reference center with expertise for rare skin diseases. Patients’ clinical characteristics were recorded. Serum concentration of 25-hydroxyvitamin D and parathyroid hormone were determined. For patients with vitamin D deficiency, serum calcium, serum phosphorus and bone mineral density were also investigated. Comparisons between groups (25-hydroxyvitamin D <10 ng/mL versus ?10 ng/mL) were conducted by univariate and multivariate logistic regression. Results Of the 53 included patients, 47 (88.7%) had serum 25-hydroxyvitamin D below the optimal level of 30 ng/mL: 18 (34%) had vitamin D sufficiency, 14 (26.4%) had vitamin D insufficiency, and 15 (28.3%) had vitamin D deficiency. A negative linear correlation was found between 25-hydroxyvitamin D and parathyroid hormone levels for the whole study population. Serum calcium and phosphorus levels were normal for the 15 patients with vitamin D deficiency. Bone mineral density was investigated for 11 of these latter 15 patients, and six of them had osteopenia. Winter/spring seasons of vitamin D measurement, severity of ichthyosis, and phototypes IV–VI were identified as independent risk factors for vitamin D deficiency. Conclusions Clinicians should be aware of the risk of vitamin D deficiency in the management of patients with inherited ichthyosis, especially in winter and spring, and in case of dark skin or severe disease. PMID:25091406

2014-01-01

386

Effects of hormone replacement therapy with vitamin C and E supplementation on plasma thyroid hormone levels in postmenopausal women with Type 2 diabetes.  

PubMed

Recent studies have shown that hormone replacement therapy (HRT) can exert regulatory affects on lipid and glucose homeostasis. It has been demonstrated that hyperglycemia also involving the formation of lipid peroxides, exert several biological effects that may contribute to the onset and progression of thyroid and kidney abnormalities of postmenopausal women Type 2 diabetes. Therefore, the aim of our study was to evaluate the effect of HRT, vitamin C and E (VCE) treatments on some plasma biochemical and hematological parameters and plasma thyroid hormone levels in postmenopausal women with or without diabetes. Oral HRT and VCE supplementation were compared with no HRT treatment in 40 non-diabetic postmenopausal women and 40 postmenopausal women with Type 2 diabetes mellitus, in a 6-week randomized prospective study. In the 20 women with diabetes who received oral HRT and the 20 women with diabetes who received HRT plus VCE, there was a significant fall in urea, uric acid, creatinine, total bilirubin, conjugated bilirubin, AST, ALT, LDH values. There was no significant change in red blood cell counts, total protein, albumin, sodium, potassium, hematocrit, hemoglobin and free thyrotoxine and triiodothyronine values in postmenopausal women with diabetes or treated with oral HRT and VCE. In conclusion, daily VCE and HRT administrations seem to produce significant improvement on biochemical parameters in the blood of postmenopausal women with Type 2 diabetes. The HRT and VCE supplementations may strengthen the antioxidant defense system and they may play a role in preventing kidney and liver diseases of postmenopausal women with Type 2 diabetes. PMID:19917523

Naziro?lu, Mustafa; Sim?ek, Mehmet

2009-12-01

387

Vitamin D insufficiency and insulin resistance in obese adolescents  

PubMed Central

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

Tosh, Aneesh K.; Belenchia, Anthony M.

2014-01-01

388

Substernal oxyphil parathyroid adenoma producing PTHrP with hypercalcemia and normal PTH level  

Microsoft Academic Search

BACKGROUND: Parathyroid adenoma is the most common cause of primary hyperparathyroidism. Preoperative serum calcium and intact-parathyroid hormone levels are the most useful diagnostic parameters that allow differentiating primary hyperparathyroidism from non-parathyroid-dependent hypercalcemia. Parathyroidectomy is the definitive treatment for primary hyperparathyroidism. Approximately 5% of patients who underwent parathyroidectomy present with persistent or recurrent hyperparathyroidism due to ectopic localization of the adenoma.

Angela Gurrado; Andrea Marzullo; Germana Lissidini; Agostino Lippolis; Domenico Rubini; Gaetano Lastilla; Mario Testini

2008-01-01

389

A Novel Rat Model of Vitamin D Deficiency: Safe and Rapid Induction of Vitamin D and Calcitriol Deficiency without Hyperparathyroidism  

PubMed Central

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.

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

390

Hormones  

MedlinePLUS

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

391

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

PubMed Central

Background: The risk of cardiovascular disease in dialysis patients is higher than the general population. Vitamin D receptors exist in myocardium inhibit cardiac hypertrophy. N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is a neurohormone secreted by the heart in response to ventricular mass increase. This study aimed to evaluate the effect of oral vitamin D on serum level of pro-B-type natriuretic peptide (pro-BNP) in peritoneal dialysis patients. Materials and Methods: In a randomized clinical trial, 84 peritoneal dialysis patients (49 males and 35 females) were randomly divided into two groups. The intervention group received 50000 units oral vitamin D per week, for 12 weeks if 25-hydroxy-vitamin D level was <10 ng/ml and for 8 weeks if it was between 10 ng/ml and 30 ng/ml. The control group received placebo. Parathyroid hormone, calcium, phosphor, 25-hydroxy-vitamin D, albumin and NT-pro-BNP were evaluated before and after the study. Results: The mean serum level of pro-BNP in patients receiving vitamin D and placebo group before the study was 875 pg/ml and 793 pg/ml, respectively. There was 895.9 pg/ml in the intervention group and 736.7 pg/ml in the control group (P = 0.7). Mean serum level of 25(OH) D in patients receiving oral vitamin D and placebo group before the study was 16.9 ng/ml and 31.9 ng/ml, respectively. There was 28.9 ng/ml in the intervention group and 12.9 ng/ml in the control group (P = 0.001). There were no significant differences regarding other indices (Alb, P, Ca, intact parathyroid hormone) between two groups. Conclusion: Vitamin D did not significantly change the serum level of pro-BNP in peritoneal dialysis patients. PMID:25625100

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

2014-01-01

392

A single injection of the anabolic bone agent, parathyroid hormone-collagen binding domain (PTH-CBD), results in sustained increases in bone mineral density for up to 12 months in normal female mice.  

PubMed

Parathyroid hormone (PTH) is the most effective osteoporosis treatment, but it is only effective if administered by daily injections. We fused PTH(1-33) to a collagen binding domain (PTH-CBD) to extend its activity, and have shown an anabolic bone effect with monthly dosing. We tested the duration of action of this compound with different routes of administration. Normal young C57BL/6J mice received a single intraperitoneal injection of PTH-CBD (320 ?g/kg). PTH-CBD treated mice showed a 22.2 % increase in bone mineral density (BMD) at 6 months and 12.8 % increase at 12 months. When administered by subcutaneous injection, PTH-CBD again caused increases in BMD, 15.2 % at 6 months and 14.3 % at 12 months. Radiolabeled PTH-CBD was concentrated in bone and skin after either route of administration. We further investigated skin effects of PTH-CBD, and histological analysis revealed an apparent increase in anagen VI hair follicles. A single dose of PTH-CBD caused sustained increases in BMD by >10 % for 1 year in normal mice, regardless of the route of administration, thus showing promise as a potential osteoporosis therapy. PMID:22806683

Ponnapakkam, Tulasi; Katikaneni, Ranjitha; Suda, Hirofumi; Miyata, Shigeru; Matsushita, Osamu; Sakon, Joshua; Gensure, Robert C

2012-09-01

393

Parathyroid hormone and prostaglandin E2 preferentially increase luciferase levels in bone of mice harboring a luciferase transgene controlled by elements of the pro-alpha1(I) collagen promoter.  

PubMed

Type I collagen is the major extracellular protein in bone, tendons, ligaments, and skin. DNA elements of the mouse pro-alpha1 (I) collagen promoter were shown to drive the bone-selective expression of a luciferase transgene. We examined whether this expression can be used to evaluate the effect of anabolic agents on bone formation in vivo. Treatment of either intact males, intact females, or ovariectomized (ovx) mice with 80 microg/kg/day of human parathyroid hormone (hPTH), for 5 to 11 days increased luciferase levels in tibiae by two- to threefold compared with vehicle-treated mice. The increases were tissue specific, as no changes in skin luciferase expression were observed. Treatment with prostaglandin E2, a potent bone anabolic agent, for 11 days also increased expression of the transgene in bone, but not in skin. Treatment with dihydrotestosterone (DHT) for 11 days increased luciferase activity in skin, but not in bone. Histomorphometric analysis revealed that 28-day treatment with PTH increased bone formation; 60-day treatment of OVX mice with DHT did not. These findings show a correlation between bone formation and the expression of a transgene driven by DNA elements of the mouse pro-alpha1 (I) collagen promoter, suggesting that this expression can be used as an indicator and provide a faster readout for the ability of agents to stimulate bone formation in this mouse strain. PMID:10617154

Opas, E E; Gentile, M A; Rossert, J A; de Crombrugghe, B; Rodan, G A; Schmidt, A

2000-01-01

394

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

PubMed Central

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

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

2014-01-01

395

Effects of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) on thyroid hormone and vitamin A levels in rats and mice  

Microsoft Academic Search

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

Sara Hallgren; Taha Sinjari; Helen Håkansson; Per Darnerud

2001-01-01

396

Ameliorative Effect of Vitamin C on Alterations in Thyroid Hormones Concentrations Induced by Subchronic Coadministration of Chlorpyrifos and Lead in Wistar Rats  

PubMed Central

The present study evaluated the ameliorative effect of vitamin C on alteration in thyroid hormones induced by low-dose subchronic coadministration of chlorpyrifos (CPF) and lead (Pb). Forty Wistar rats were divided into 4 groups of 10 animals each. Groups I and II were administered soya oil (2?mL/kg) and vitamin C (100?mg/kg), respectively. Group III was coadministered CPF (4.25?mg/kg ~1/20th LD50) and Pb (250?mg/kg ~1/20th LD50), respectively. Group IV was pretreated with vitamin C (100?mg/kg) and then coadministered with CPF (4.25?mg/kg) and Pb (250?mg/kg), 30?min later. The regimens were administered by gavage for a period of 9 weeks. The marginal decrease in serum triiodothyronine and thyroxine and the significant increase in the concentrations of thyroid stimulating hormone and malonaldehyde in the group coadministered with CPF and Pb were ameliorated by vitamin C partly due to its antioxidant properties. PMID:21687644

Ambali, Suleiman F.; Orieji, Chinedu; Abubakar, Woziri O.; Shittu, Muftau; Kawu, Mohammed U.

2011-01-01

397

Abnormal Parathyroid Cell Proliferation Precedes Biochemical Abnormalities in a Mouse Model of Primary Hyperparathyroidism  

Microsoft Academic Search

The properties of neoplastic proliferation and hor- monal dysregulation are tightly linked in primary hyperparathyroidism (HPT). However, whether ab- normal parathyroid proliferation is the cause or result of a shift in calcium-sensitive parathyroid hormonal regulation has been controversial. We addressed this issue by analyzing the temporal se- quence of these fundamental abnormalities in a mouse model of primary HPT. These

Sanjay M. Mallya; James J. Gallagher; Yvette K. Wild; Olga Kifor; Jessica Costa-Guda; Kirsten Saucier; Edward M. Brown; Andrew Arnold

2005-01-01

398

Nasal administration of a novel recombinant human parathyroid hormone (1-34) analog for the treatment of osteoporosis of ovariectomized rats.  

PubMed

Synthetic human parathyroid (1-34) (hPTH (1-34)) is known to have the full biological activity of the holohormone for osteoporosis. This study is about designing a novel analog of hPTH (1-34) which is more suitable for intranasal administration. We likewise evaluate effectiveness of the nasal drops against osteoroporosis. Through fusion expression of combining gene, cell disruption, inclusion body washing, ethanol fraction precipitation, acid hydrolysis, and CM-52 ion exchange column chromatography Pro-Pro-[Arg¹¹] hPTH (1-34)-Pro-Pro was designed and produced. Nasal drops of Pro-Pro-[Arg¹¹] hPTH (1-34)-Pro-Pro were prepared and administrated to ovariectomized rats. After 12 weeks of raising, Bone Material Densities (BMD) of vertebrae were examined by Dual Energy X-Ray Absorptiometry (DEXA). The average BMD of these groups treated with nasal drops of the peptide were 28.0%-47.2% (P<0.01) higher than that of the group treated with normal saline (NS). The subchondral bone plates of the femoral heads were examined by scanning electron microscopy and a defined planar section was photographed. Percentage of the area of the cancellous bone was calculated. Percentages of the groups treated with nasal drops of the peptide increased; values were significantly different to that of the group treated with NS (P<0.001) and were even equivalent to that of normal groups. These results show that nasal drops of Pro-Pro-[Arg¹¹] hPTH (1-34)-Pro-Pro are effective against osteoporosis. PMID:21664384

Shi, Xiaoming; Wang, Chunxiao; Zhuang, Zhihua; Lu, Jingning; Liu, Jingjing; Wu, Jie; Cao, Rongyue; Li, Taiming

2011-10-10

399

Functioning Oxyphil Adenoma of Parathyroid Gland  

PubMed Central

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