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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.



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.



The thyroid hormone, parathyroid hormone and vitamin D associated hypertension.  


Thyroid disorders and primary hyperparathyroidism have been known to be associated with increases in blood pressure. The hypertension related to hypothyroidism is a result of increased peripheral resistance, changes in renal hemodynamics, hormonal changes and obesity. Treatment of hypothyroidism with levo-thyroxine replacement causes a decrease in blood pressure and an overall decline in cardiovascular risk. High blood pressure has also been noted in patients with subclinical hypothyroidism. Hyperthyroidism, on the other hand, is associated with systolic hypertension resulting from an expansion of the circulating blood volume and increase in stroke volume. Increased serum calcium levels associated with a primary increase in parathyroid hormone levels have been also associated with high blood pressure recordings. The mechanism for this is not clear but the theories include an increase in the activity of the renin-angiotensin-aldosterone system and vasoconstriction. Treatment of primary hyperparathyroidism by surgery results in a decline in blood pressure and a decrease in the plasma renin activity. Finally, this review also looks at more recent evidence linking hypovitaminosis D with cardiovascular risk factors, particularly hypertension, and the postulated mechanisms linking the two. PMID:22145139

Chopra, Sandeep; Cherian, Davis; Jacob, Jubbin J



The Control of Calcium Metabolism by Parathyroid Hormone, Calcitonin and Vitamin D.  

National Technical Information Service (NTIS)

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 t...

J. T. Potts



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



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


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

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



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.



Optimal vitamin D status and serum parathyroid hormone concentrations in African American women13  

Microsoft Academic Search

Background: Optimal vitamin D status for the prevention of osteo- porosis has been inferred from examinations of the serum 25- hydroxyvitamin D (25(OH)D) concentration below which there is an increase in serum parathyroid hormone (PTH). Objective: The objectives of the study were to ascertain whether a threshold for serum 25(OH)D exists below which serum PTH in- creases and whether persons

John F Aloia; Sonia A Talwar; Simcha Pollack; Martin Feuerman; James K Yeh


Regulation by Vitamin D Metabolites of Messenger Ribonucleic Acid for Preproparathyroid Hormone in Isolated Bovine Parathyroid Cells  

Microsoft Academic Search

We have recently determined that high calcium concentrations, in parallel with their suppressive effects on parathyroid hormone (PTH) secretion, reversibly and specifically decrease preproPTH mRNA in cultured bovine parathyroid cells. In order to determine whether vitamin D metabolites also regulate the content of preproPTH mRNA, we tested their effects on bovine parathyroid cells in the same culture system. Levels of

Justin Silver; John Russell; Louis M. Sherwood



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.



Relationship between Vitamin D, Parathyroid Hormone, and Bone Health  

PubMed Central

Context: There is a controversy regarding the definition of vitamin D insufficiency as it relates to bone health. Objective: The objective of the study was to examine the evidence for a threshold value of serum 25-hydroxyvitamin D (25OHD) that defines vitamin D insufficiency as it relates to bone health. Design and Participants: This was a cross-sectional analysis of baseline data in 488 elderly Caucasian women, mean age 71 yr, combined with a literature review of 70 studies on the relationship of serum PTH to serum 25OHD. Setting: The study was conducted in independent-living women in the midwest United States. Main Outcome Measure: The relationship between serum 25OHD, serum PTH, and serum osteocalcin and 24-h urine N-telopeptides was evaluated. Results: Serum PTH was inversely correlated with serum 25OHD (r = ?0.256, P < 0.0005), but no threshold as defined by suppression of serum PTH was found within the serum 25OHD range 6–60 ng/ml (15–150 nmol/liter). However, in contrast, there was a threshold for bone markers, serum osteocalcin and urine N-telopeptides, that increased only below a serum 25OHD of approximately 18 ng/ml (45 nmol/liter). Calcium absorption was not correlated with serum PTH and serum 25OHD, and no threshold was found. A literature review of 70 studies generally showed a threshold for serum PTH with increasing serum 25OHD, but there was no consistency in the threshold level of serum 25OHD that varied from 10 to 50 ng/ml (25–125 nmol/liter). Conclusions: Vitamin D insufficiency should be defined as serum 25OHD less than 20 ng/ml (50 nmol/liter) as it relates to bone.

Walters, R. W.; Fang, X.; Gallagher, J. C.



Relationship between Vitamin D, Parathyroid Hormone, and Bone Mineral Density in Elderly Koreans  

PubMed Central

There is controversy regarding definition of vitamin D inadequacy. We analyzed threshold 25-hydroxyvitamin D (25[OH]D) below which intact parathyroid hormone (iPTH) increases, and examined age- and sex-specific changes of 25(OH)D and iPTH, and association of 25(OH)D and iPTH with bone mineral density (BMD) in elderly Koreans. Anthropometric parameters, serum 25(OH)D and iPTH, lumbar spine and femur BMD by dual-energy radiography absorptiometry (DXA) were measured in 441 men and 598 postmenopausal women. iPTH increased below serum 25(OH) of 36.7 ng/mL in men, but failed to reach plateau in women. Femur neck BMD above and below threshold differed when threshold 25(OH)D concentrations were set at 15-27.5 ng/mL in men, and 12.5-20 ng/mL in postmenopausal women. Vitamin D-inadequate individuals older than 75 yr had higher iPTH than those aged ? 65 yr. In winter, age-associated iPTH increase in women was steeper than in summer. In conclusion, vitamin D inadequacy threshold cannot be estimated based on iPTH alone, and but other factors concerning bone health should also be considered. Older people seemingly need higher 25(OH)D levels to offset age-associated hyperparathyroidism. Elderly vitamin D-inadequate women in the winter are most vulnerable to age-associated hyperparathyroidism.

Kim, Guilsun; Oh, Ki Won; Jang, Eun-Hee; Kim, Mee-Kyoung; Lim, Dong-Jun; Kwon, Hyuk Sang; Baek, Ki-Hyun; Yoon, Kun-Ho; Lee, Won Chul; Cha, Bong Yun; Lee, Kwang-Woo; Son, Ho-Young



Human Parathyroid Hormone.  

National Technical Information Service (NTIS)

The patent application relates to the isolation and purification of human parathyroid hormone from human parathyroid adenomas. The primary sequence of the amino terminal 34 residues was determined and the peptide of the first 34 residues synthesized.

H. B. Brewer



Vitamin d status and parathyroid hormone concentrations influence the skeletal response to zoledronate and denosumab.  


Studies suggest that optimal vitamin D status is required for the maximal effect of antiresorptive agents. We investigated the relationship between vitamin D status, serum parathyroid hormone (PTH) concentrations, and change in bone mineral density (BMD) following iv zoledronate and denosumab. We carried out a retrospective analysis of 111 patients, mean age 70 (SD 13) years, 89 women and 22 men, prescribed zoledronate and 43 postmenopausal women treated with denosumab for osteoporosis. We measured BMD at the lumbar spine (LS) and total hip (TH), serum 25 (OH) vitamin D, PTH, and bone turnover markers (plasma CTX, P1NP) at 1 year. In patients on zoledronate, BMD increased at the LS and TH (mean LS change [SEM] = 2.6 % [0.5 %], mean TH change = 1.05 % [0.5 %], p < 0.05). A significant increase in BMD was seen at the LS only in the denosumab group (p = 0.001). Significant decreases in CTX and P1NP were observed at 12 months in both treatment groups. At baseline and at 12 months, 34 % and 23 % of the patients on zoledronate had a serum vitamin D of <50 nmol/L, respectively. The mean PTH concentration in patients with 25 (OH) vitamin D <50 nmol/L was 44 ng/L (SEM 16.6). Patients with PTH concentration <44 ng/L had significantly higher increases in TH BMD compared to those with PTH >44 ng/L (zoledronate 1.9 [0.83] vs. -0.43 [0.81], p = 0.04; denosumab 4.1 [0.054] vs. -1.7 [0.04], p = 0.004). Optimal vitamin D status and PTH concentrations improve the skeletal response to zoledronate and denosumab. PMID:24509506

Mosali, P; Bernard, L; Wajed, J; Mohamed, Z; Ewang, M; Moore, A; Fogelman, I; Hampson, G



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

PubMed Central

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

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



Vitamin D deficiency in Korean children: prevalence, risk factors, and the relationship with parathyroid hormone levels  

PubMed Central

Purpose This study was performed to investigate the relationship between serum vitamin D and parathyroid hormone (PTH) levels as well as to describe the prevalence and the risk factors of vitamin D deficiency (VDD) in Korean children. Methods Participants were 1,212 children aged 4 to 15 years, who visited Bundang CHA Medical Center (located at 37°N) between March 2012 and February 2013. Overweight was defined as body mass index?85th percentile. Participants were divided into 4 age groups and 2 seasonal groups. VDD was defined by serum 25-hydroxyvitamin D (25OHD) <20 ng/mL. Results The level of 25OHD was significantly lower in overweight group than in normal weight group (17.1±5.1 ng/mL vs. 19.1±6.1 ng/mL, P<0.001). Winter-spring season (odds ratio [OR], 4.46; 95% confidence interval [CI], 3.45-5.77), older age group (OR, 1.60; 95% CI, 1.36-1.88), and overweight (OR, 2.21; 95% CI, 1.62-3.01) were independently related with VDD. The PTH levels were significantly higher in VDD group compared to vitamin D insufficiency and sufficiency group (P<0.001). In normal weight children, 25OHD (?=-0.007, P<0.001) and ionized calcium (?=-0.594, P=0.007) were independently related with PTH, however, these associations were not significant in overweight children. Conclusion VDD is very common in Korean children and its prevalence increases in winter-spring season, in overweight children and in older age groups. Further investigation on the vitamin D and PTH metabolism according to adiposity is required.

Chung, In Hyuk; Kim, Hae Jung; Chung, Sochung



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



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

Microsoft Academic Search

Abstract Vitamin D (25(OH)D) increases the eciency,of intestinal calcium absorp- tion. Low levels of serum calcium stimulate the secretion of parathyroid hor- mone (PTH), which maintains serum calcium levels at the expense of increased bone turnover, bone loss and increased risk of fractures. We studied the associa- tion between 25(OH)D and PTH levels, and their associations with bone mineral density



Vitamin D, Parathyroid Hormone, and Blood Pressure in the National Health and Nutrition Examination Surveys  

Microsoft Academic Search

BackgroundPrevious research shows serum 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) are each associated with blood pressure (BP), but it is unclear whether these associations are independent.MethodsCross-sectional data from the US National Health and Nutrition Examination Surveys (NHANES) during 2003–2006. Analyses were restricted to 7,561 participants aged ?20 years with measurements of 25(OH)D, PTH, BP, BP treatment, smoking, physical activity,

Jack L. He; Robert K. Scragg



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.



Serum intact parathyroid hormone in a random population sample of men and women: Relationship to anthropometry, life-style factors, blood pressure, and vitamin D  

Microsoft Academic Search

Intact parathyroid hormone (PTH) in serum was determined in a random population sample and was related to age, sex, body composition, life-style factors, blood pressure, blood lipids, plasma fibrinogen, and serum IGF-1, osteocalcin, and vitamin D. Within the framework of the WHO MONICA Project in the city of Göteborg, Sweden, 181 men and 166 women aged 25–64 years were studied.

K. Landin-Wilhelmsen; L. Wilhelmsen; G. Lappas; T. Rosén; G. Lindstedt; P.-A. Lundberg; J. Wilske; B.-Å. Bengtsson



Calcimimetics or vitamin D analogs for suppressing parathyroid hormone in end-stage renal disease: time for a paradigm shift?  

Microsoft Academic Search

Considerable advances have been made in the understanding of the pathogenesis and treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). These include the discovery that the calcium-sensing receptor has an important role in the regulation of parathyroid gland function, the development of calcimimetics to target this receptor, the recognition that vitamin D receptor activation has important functions beyond

James B Wetmore; L Darryl Quarles



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

PubMed Central

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



Peripheral Metabolism of Parathyroid Hormone.  

National Technical Information Service (NTIS)

It has been many years since the discovery of the heterogeneity of circulating, immunologicaly detectable parathyroid hormone (iPTH) and the demonstration that the structural requirements for biologic activity of PTH reside in the first 34 amino acid resi...

W. F. Neuman N. Schneider R. Doolittle



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.

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



The Ratio of Parathyroid Hormone to Vitamin D Is a Determinant of Cardiovascular Risk and Insulin Sensitivity in Adolescent Girls  

PubMed Central

Abstract Background Vitamin D insufficiency and higher testosterone are common in obese girls and may adversely affect glucose homeostasis and cardiovascular risk. Data are conflicting regarding the impact of parathyroid hormone (PTH) on these factors. Our objective was to determine associations of 25-hydroxyvitamin D (25-OHD), PTH, and testosterone with measures of glucose homeostasis and cardiovascular risk in adolescent girls after controlling for regional adiposity, with the hypothesis that lower 25-OHD, a higher PTH or PTH/25-OHD ratio, and higher testosterone would be associated with lower insulin sensitivity and greater cardiovascular risk. Methods A total of 15 obese girls and 15 matched normal weight controls (12–18 years) underwent fasting measurements of 25-OHD, PTH, testosterone, sex hormone-binding globulin (SHBG), high-sensitivity C-reactive protein (hsCRP), oral glucose tolerance testing, and quantification of visceral (VAT) and subcutaneous (SAT) fat by magnetic resonance imaging (MRI). Results There were no associations of 25-OHD with measures of glucose homeostasis or hsCRP. In contrast, PTH and PTH/25-OHD were associated negatively with homeostasis model assessment of insulin resistance (HOMA-IR) and positively with quantitative insulin sensitivity check index (QUICKI) in obese girls but not controls. These associations remained significant after controlling for body mass index standard deviation score (BMI-SDS), but not for VAT. On regression modeling, PTH/25-OHD was positively associated with hsCRP after controlling for BMI-SDS or VAT. Free testosterone positively predicted the corrected insulin response. Conclusions In obese girls, PTH/25-OHD is positively associated with measures of insulin sensitivity and hsCRP. Further studies are needed to investigate the relationship between PTH and glucose homeostasis in obesity.

Stanley, Takara; Bredella, Miriam A.; Pierce, Lisa



Parathyroid hormone gene expression in hypophosphatemic rats.  

PubMed Central

Phosphate is central to bone metabolism and we have therefore studied whether parathyroid hormone (PTH) is regulated by dietary phosphate in vivo. Weanling rats were fed diets with different phosphate contents for 3 wk: low phosphate (0.02%), normal calcium (0.6%), normal phosphate (0.3%), and calcium (0.6%); high phosphate (1.2%), high calcium (1.2%). The low phosphate diet led to hypophosphatemia, hypercalcemia, and increased serum 1,25(OH)2D3 together with decreased PTH mRNA levels (25 +/- 8% of controls, P < 0.01) and serum immunoreactive PTH (4.7 +/- 0.8: 22.1 +/- 3.7 pg/ml; low phosphate: control, P < 0.05). A high phosphate diet led to increased PTH mRNA levels. In situ hybridization showed that hypophosphatemia decreased PTH mRNA in all the parathyroid cells. To separate the effect of low phosphate from changes in calcium and vitamin D rats were fed diets to maintain them as vitamin D-deficient and normocalcemic despite the hypophosphatemia. Hypophosphatemic, normocalemic rats with normal serum 1,25(OH)2D3 levels still had decreased PTH mRNAs. Nuclear transcript run-ons showed that the effect of low phosphate was posttranscriptional. Calcium and 1,25(OH)2D3 regulate the parathyroid and we now show that dietary phosphate also regulates the parathyroid by a mechanism which remains to be defined. Images

Kilav, R; Silver, J; Naveh-Many, T



Parathyroid adenoma  


... by the body. They do this by producing parathyroid hormone, or PTH. PTH helps control calcium, phosphorus, and ... tests are done to check the levels of parathyroid hormone, calcium , phosphorus , and vitamin D. A 24-urine ...


Parathyroid hormone - Secretion and metabolism in vivo.  

NASA Technical Reports Server (NTRS)

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

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



Vitamin D-fortified milk achieves the targeted serum 25-hydroxyvitamin D concentration without affecting that of parathyroid hormone in New Zealand toddlers.  


For young children, the level of vitamin D required to ensure that most achieve targeted serum 25-hydroxyvitamin D [25(OH)D] ?50 nmol/L has not been studied. We aimed to investigate the effect of vitamin D-fortified milk on serum 25(OH)D and parathyroid hormone (PTH) concentrations and to examine the dose-response relationship between vitamin D intake from study milks and serum 25(OH)D concentrations in healthy toddlers aged 12-20 mo living in Dunedin, New Zealand (latitude 46°S). Data from a 20-wk, partially blinded, randomized trial that investigated the effect of providing red meat or fortified toddler milk on the iron, zinc, iodine, and vitamin D status in young New Zealand children (n = 181; mean age 17 mo) were used. Adherence to the intervention was assessed by 7-d weighed diaries at wk 2, 7, 11, 15, and 19. Serum 25(OH)D concentration was measured at baseline and wk 20. Mean vitamin D intake provided by fortified milk was 3.7 ?g/d (range, 0-10.4 ?g/d). After 20 wk, serum 25(OH)D concentrations but not PTH were significantly different in the milk groups. The prevalence of having a serum 25(OH)D <50 nmol/L remained relatively unchanged at 43% in the meat group, whereas it significantly decreased to between 11 and 15% in those consuming fortified study milk. In New Zealand, vitamin D intake in young children is minimal. Our findings indicate that habitual consumption of vitamin D-fortified milk providing a mean intake of nearly 4 ?g/d was effective in achieving adequate year-round serum 25(OH)D for most children. PMID:21832027

Houghton, Lisa A; Gray, Andrew R; Szymlek-Gay, Ewa A; Heath, Anne-Louise M; Ferguson, Elaine L



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.

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



Parathyroid hormone and bone biomechanics  

Microsoft Academic Search

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

Matthew R. Allen; David B. Burr



Parathyroid Hormone and Bone Healing  

Microsoft Academic Search

Fracture healing is a complex process, and a significant number of fractures are complicated by impaired healing and non-union.\\u000a Impaired healing is prevalent in certain risk groups, such as the elderly, osteoporotics, people with malnutrition, and women\\u000a after menopause. Currently, no pharmacological treatments are available. There is therefore an unmet need for medications\\u000a that can stimulate bone healing. Parathyroid hormone

M. Ellegaard; N. R. Jørgensen; P. Schwarz



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.



Parathyroid hormone-related protein blood test  


... measures the level of a hormone in the blood, called parathyroid hormone-related protein. ... Increased levels of PTH-related protein with high blood calcium ... be produced by many different kinds of cancers, including those ...


Racial differences in the relationship between vitamin D, bone mineral density, and parathyroid hormone in the National Health and Nutrition Examination Survey  

PubMed Central

Summary It is unclear whether optimal levels of 25-hydroxyvitamin D (25(OH)D) in whites are the same as in minorities. In adult participants of NHANES, the relationships between 25(OH)D, bone mineral density (BMD), and parathyroid hormone (PTH) differed in blacks as compared to whites and Mexican-Americans, suggesting that optimal 25(OH)D levels for bone and mineral metabolism may differ by race. Introduction Blacks and Hispanics have lower 25-hydroxyvitamin D concentrations than whites. However, it is unclear whether 25(OH)D levels considered “optimal” for bone and mineral metabolism in whites are the same as those in minority populations. Methods We examined the relationships between 25(OH)D and parathyroid hormone in 8,415 adult participants (25% black and 24% Mexican-American) in the National Health and Nutrition Examination Surveys 2003–2004 and 2005–2006; and between 25(OH)D and bone mineral density in 4,206 adult participants (24% black and 24% Mexican-American) in the 2003–2004 sample. Results Blacks and Mexican-Americans had significantly lower 25(OH)D and higher PTH concentrations than whites (P<0.01 for both). BMD significantly decreased (P<0.01) as serum 25(OH)D and calcium intake declined among whites and Mexican-Americans, but not among blacks (P=0.2). The impact of vitamin D deficiency (25 (OH)D?20 ng/ml) on PTH levels was modified by race/ethnicity (P for interaction, 0.001). Whereas inverse relationships between 25(OH)D and PTH were observed above and below a 25(OH)D level of 20 ng/ml in whites and Mexican-Americans, an inverse association between 25(OH)D and PTH was only observed below this threshold in blacks, with the slope of the relationship being essentially flat (P=0.7) above this cut-point, suggesting that PTH may be maximally suppressed at lower 25(OH)D levels in blacks than in whites or Mexican-Americans. Conclusions The relationships between 25(OH)D, BMD, and PTH may differ by race among US adults. Whether race-specific ranges of optimal vitamin D are needed to appropriately evaluate the adequacy of vitamin D stores in minorities requires further study.

Farwell, W. R.; Kermah, D.; Taylor, E. N.



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.

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



An assessment of parathyroid hormone, calcitonin, 1,25 (OH) 2 vitamin D3, estradiol and testosterone in men with active calcium stone disease and evaluation of its biochemical risk factors  

Microsoft Academic Search

The aim of this study is to investigate the serum levels of parathyroid hormone (PTH), calcitonin, 1,25 (OH)2 vitamin D3, estradiol and testosterone in male patients with active renal calcium stone disease compared with controls and\\u000a investigate their relationship with serum\\/urinary biochemistry. Male active renal calcium stone formers (ASF) were enrolled\\u000a from December 2008 to April 2009. Controls were selected

Nasser ShakhssalimKobra; Kobra Roohi Gilani; Mahmoud Parvin; Peyman Mohammadi Torbati; Amir H. Kashi; Mohaddeseh Azadvari; Banafsheh Golestan; Abbas Basiri



Dietary Intake of Vitamin D in Premenopausal, Healthy Vegans was Insufficient to Maintain Concentrations of Serum 25-hydroxyvitamin D and Intact Parathyroid Hormone Within Normal Ranges During the Winter in Finland  

Microsoft Academic Search

Objective To study vitamin D status and bone metabolism of premenopausal vegetarians and omnivores during a 1-year period.Design Longitudinal, observational study. Bone mineral density was measured, blood samples from fasting subjects were obtained, and 24-hour urinary samples were collected in February 1994, August 1994, and January 1995. Serum 25-hydroxyvitamin D [S-25(OH)D] and intact parathyroid hormone (Si-PTH) concentrations were measured and




Polypeptide Derivatives of Parathyroid Hormone (PTH).  

National Technical Information Service (NTIS)

Novel parathyroid hormone (PTH) polypeptide derivatives are disclosed, as are pharmaceutical compositions containing said polypeptides, and synthetic and recombinant methods for producing said polypeptides. Also disclosed are methods for treating mammalia...

H. Juppner H. M. Kronenberg J. T. Potts T. J. Gardella



The Calcimimetic Agent AMG 073 Lowers Plasma Parathyroid Hormone Levels in Hemodialysis Patients with Secondary Hyperparathyroidism  

Microsoft Academic Search

Treatment with vitamin D sterols can lower plasma parathyroid hormone (PTH) in many patients with secondary hyperparathyroidism due to end-stage renal disease, but hyper- calcemia, hyperphosphatemia, or both often develop during treatment. As such, alternative therapeutic approaches to man- aging excess PTH secretion are needed. Calcimimetic agents directly inhibit PTH secretion by activating the calcium-sens- ing receptor in the parathyroid



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

Microsoft Academic Search

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

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



Osteoporotic fracture and parathyroid hormone  

PubMed Central

Osteoporosis and age-related bone loss is associated with changes in bone remodeling characterized by decreased bone formation relative to bone resorption, resulting in bone fragility and increased risk of fractures. Stimulating the function of bone-forming osteoblasts, is the preferred pharmacological intervention for osteoporosis. Recombinant parathyroid hormone (PTH), PTH(1-34), is an anabolic agent with proven benefits to bone strength and has been characterized as a potential therapy for skeletal repair. In spite of PTH’s clinical use, safety is a major consideration for long-term treatment. Studies have demonstrated that intermittent PTH treatment enhances and accelerates the skeletal repair process via a number of mechanisms. Recent research into the molecular mechanism of PTH action on bone tissue has led to the development of PTH analogs to control osteoporotic fractures. This review summarizes a number of advances made in the field of PTH and bone fracture to combat these injuries in humans and in animal models. The ultimate goal of providing an alternative to PTH, currently the sole anabolic therapy in clinical use, to promote bone formation and improve bone strength in the aging population is yet to be achieved.

Datta, Nabanita S



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

PubMed Central

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

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



A vitamin D analogue (EB1089) inhibits parathyroid hormone-related peptide production and prevents the development of malignancy-associated hypercalcemia in vivo.  

PubMed Central

We have examined the effects of 1,25 dihydroxyvitamin D3 (1,25[OH]2D3) and a low calcemic analogue EB1089 on parathyroid hormone-related peptide (PTHRP) production and on the development of hypercalcemia in Fischer rats implanted with the Leydig cell tumor H-500. Leydig cell tumors were implanted subcutaneously into male Fischer rats, which received constant infusions intraperitoneally of either 1,25(OH)2D3 (50-200 pmol/24 h), EB1089 (50-400 pmol/24 h), or vehicle for up to 4 wk. A control group of animals received similar infusions without tumor implantation. Plasma calcium, plasma levels of immunoreactive iPTHRP, and tumor PTHRP mRNA levels were determined as well as tumor size, animal body weight, and animal survival time. Non-tumor-bearing animals receiving > 50 pmol/24 h of 1,25(OH)2D3 became hypercalcemic, whereas no significant change in plasma calcium was observed in animals receiving < or = 200 pmol/24 h of EB1089. Tumor-bearing animals receiving vehicle alone or > 50 pmol/24 h of 1,25(OH)2D3 became severely hypercalcemic within 15 d. However, animals treated with low dose 1,25(OH)2D3 and all doses of EB1089 maintained near-normal or normal levels of plasma calcium for up to 4 wk. Additionally, reduced levels of tumor PTHRP mRNA and of plasma iPTHRP were observed compared with controls in both vitamin D- and EB1089-treated rats. Infusion of 50 pmol/24 h of 1,25(OH)2D3 and 200 pmol/24 h of EB1089 significantly reduced tumor volume by the end of experiment. The analogue but not 1,25(OH)2D3 substantially prolonged survival time in tumor-bearing animals with longer survival achieved at the highest dose, 400 pmol/24 h, of EB1089. These studies demonstrate that 1,25(OH)2D3 and a low calcemic vitamin D analogue are potent inhibitors of PTHRP production in vivo. Low calcemic analogues may therefore represent important alternative therapy for malignancy-associated hypercalcemia. Images

Haq, M; Kremer, R; Goltzman, D; Rabbani, S A



Suppression of parathyroid hormone secretion in hemodialysis patients by a novel vitamin D analogue: 19-nor-1,25-dihydroxyvitamin D2  

Microsoft Academic Search

In this double-blind, placebo-controlled, randomized, multicenter study, 35 patients with end-stage renal disease undergoing maintenance hemodialysis were treated three times weekly for 4 weeks with either 19- nor-1,25-dihydroxyvitamin D2 (paricalcitol) intravenously at doses ranging from 0.04 to 0.24 microg\\/kg or placebo. Eligible patients with secondary hyperparathyroidism (HPT; intact parathyroid hormone [iPTH] level > 300 pg\\/mL) were initially withdrawn from any

F Llach; G Keshav; MV Goldblat; JS Lindberg; R Sadler; J Delmez; J Arruda; A Lau; E Slatopolsky



Parathyroid carcinosarcoma: a rare form of parathyroid carcinoma with normal parathyroid hormone levels.  


Parathyroid carcinosarcoma was first described by Nacamuli et al in 2002. We present the second case of this rare disease. This rare carcinosarmoca presented as a parathyroid carcinoma with uncharacteristically normal parathyroid hormone levels. The patient is a 57-year-old woman with long-standing right-sided vocal cord paralysis presented with a progressive 3 × 2 × 3 cm mass in the right neck. She had previously undergone a total thyroidectomy revealing benign pathology. Parathyroid hormone and calcium blood levels were within normal limits. The mass was removed with negative surgical margins. Histopathology and immunohistochemical analysis showed a biphasic pattern, with positive for chromogranin and vimentin, consistent with carcinoma and sarcoma. The disease in our patient, as in the previously reported case, has shown systemic progression despite aggressive surgical resection and adjuvant therapy. PMID:23493876

Taggart, James L; Summerlin, Don-John; Moore, Michael G



Vitamin D metabolism and parathyroid function in man.  


1. The metabolism of an intravenous pulse dose of double-isotope-labelled cholecalciferol has been studied in control subjects with widely differing states of vitamin D nutrition and in patients with primary disorders of parathyroid function. 2. The formation of labelled 1,25-dihydroxy-cholecalciferol [1,25-(OH)2D3] and labelled 24,25-dihydroxycholecalciferol [24,25-(OH)2D3] has been related to the prevailing concentrations in serum of 25-hydroxycholecalciferol [25-(OH)D3], immunoreactive parathyroid hormonel, calcium and orthophosphate (Pi). 3. In control subjects with relative vitamin D deficiency [serum 25-(OH)2D3 was related inversely to the serum 25-(OH)D3 and serum calcium, and directly to serum immunoreactive parathyroid hormone. No formation of 1,25-(OH)2D3 was detectable to form labelled 24,25(OH)2D3 preferentially. 4. No control subject produced significant amounts of both labelled 1,25-(OH)2D3 and labelled 24,25-(OH)2D3 simultaneously. 5. All subjects with primary hyperparathyroidism produced significant amounts of labelled 1,25-(OH)2D3 and labelled 24,25-(OH)2D3 simultaneously; the renal turnover of 25-(OH)D3 was apparently greater than in nutritionally matched controls. Serum labelled 1,25-(OH)2D3 in this disease was not correlated with serum 25-(OH)D3, immunoreactive parathyroid hormone, calcium or Pi. Production of labelled 24,25-(OH)2D3 was inappropriately high for the prevailing nutritional state. 6. The indirectly estimated their concentration of 1,25-(OH)2D3 showed only a fourfold variation in control subjects (45-180 pmol/l), compatible with its having a regulated hormonal function. 7. The data suggest that the production of 1,25-(OH)2D3 from a pulse dose of cholecalciferol is normally regulated, directly or indirectly, by the parathyroid hormone. PMID:165031

Mawer, E B; Backhouse, J; Hill, L F; Lumb, G A; De Silva, P; Taylor, C M; Stanbury, S W



Determination of Hormone Parathyroid by Radioimmunoassay.  

National Technical Information Service (NTIS)

The labelling of bovine parathyroid hormone and its employment for the determination of seric PTH by radioimmunoanalysis is described. The specific activity of exp 131 I PTH is 200-350mCi/mg and the damage 3-5%. The method used for radioimmunoanalysis was...

C. Fisher-Ferraro M. Moos de Ephraim C. Mautalen A. E. A. Mitta



The regulation of parathyroid hormone secretion and synthesis.  


Secondary hyperparathyroidism classically appears during the course of chronic renal failure and sometimes after renal transplantation. Understanding the mechanisms by which parathyroid hormone (PTH) synthesis and secretion are normally regulated is important in devising methods to regulate overactivity and hyperplasia of the parathyroid gland after the onset of renal insufficiency. Rapid regulation of PTH secretion in response to variations in serum calcium is mediated by G-protein coupled, calcium-sensing receptors on parathyroid cells, whereas alterations in the stability of mRNA-encoding PTH by mRNA-binding proteins occur in response to prolonged changes in serum calcium. Independent of changes in intestinal calcium absorption and serum calcium, 1?,25-dihydroxyvitamin D also represses the transcription of PTH by associating with the vitamin D receptor, which heterodimerizes with retinoic acid X receptors to bind vitamin D-response elements within the PTH gene. 1?,25-Dihydroxyvitamin D additionally regulates the expression of calcium-sensing receptors to indirectly alter PTH secretion. In 2°HPT seen in renal failure, reduced concentrations of calcium-sensing and vitamin D receptors, and altered mRNA-binding protein activities within the parathyroid cell, increase PTH secretion in addition to the more widely recognized changes in serum calcium, phosphorus, and 1?,25-dihydroxyvitamin D. The treatment of secondary hyperparathyroidism by correction of serum calcium and phosphorus concentrations and the administration of vitamin D analogs and calcimimetic agents may be augmented in the future by agents that alter the stability of mRNA-encoding PTH. PMID:21164021

Kumar, Rajiv; Thompson, James R



Attenuated Rise of 1,25 (OH)2 Vitamin D3 in Response to Parathyroid Hormone in Patients with Incipient Renal Failure  

Microsoft Academic Search

Despite elevated parathyroid hormone (PTH) levels, low normal or diminished serum 1,25(OH)2D3 concentrations are found in patients with incipient renal failure. To further assess (indirectly) the reserve capacity of renal production of 1,25(OH)2D3 we studied 9 patients with incipient or moderate renal failure (inulin clearance 31–68ml\\/min\\/1.73 m2) and 9 controls, using a novel stimulation test. We measured 1,25 (OH)2D3 levels,

E. Ritz; A. Seidel; H. Ramisch; A. Szabo; R. Bouillon



Parathyroid hormone and calcitonin in glucose regulation  

Microsoft Academic Search

Blood glucose, insulin, calcium (Ca), phosphorus (P), parathyroid hormone (PTH) and calcitonin (CT) were evaluated in 8 normal children, aged 17–41 months, during an oral glucose load; in 7 normal children, aged 15–42 months, during i.v. glucose infusion; and in 6 normal children, aged 19–40 months, during glucagon administration. During the oral glucose tolerance tests the mean maximum decline of

G. Zamboni; A. Albertini; G. Zopii; M. Cecchettin



Further evidence for a parathyroid hormone-related protein in fetal parathyroid glands of sheep.  


Extracts of ovine fetal parathyroid glands contained a substance in addition to parathyroid hormone (PTH) which could not be neutralized by antiserum against PTH in a cytochemical bioassay. This substance reacted similarly to human parathyroid hormone-related protein, the humoral hypercalcaemic factor associated with malignancy in man. The ovine fetal PTHrP may be responsible for maintaining the fetus hypercalcaemic relative to the mother. PMID:3231705

Loveridge, N; Caple, I W; Rodda, C; Martin, T J; Care, A D



Oral calcium supplementation reverses the biochemical pattern of parathyroid hormone resistance in underprivileged Indian toddlers  

Microsoft Academic Search

Background:Toddlers in Pune, India, accustomed to low dietary calcium intake but vitamin D replete have low serum ionised calcium and inappropriately raised serum inorganic phosphorus concentrations together with elevated serum parathyroid hormone (PTH) concentrations. We hypothesised that dietary calcium deficiency leads to end organ resistance to PTH, thus resulting in mild hypocalcaemia and hyperphosphataemia, and that this would be reversed

A Khadilkar; M Z Mughal; N Hanumante; M Sayyad; N Sanwalka; S Naik; W D Fraser; A Joshi; V Khadilkar



Effect of phorbol myristate acetate on secretion of parathyroid hormone  

Microsoft Academic Search

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




Associations between serum-intact parathyroid hormone, serum 25-hydroxyvitamin d, oral vitamin d analogs and metabolic syndrome in peritoneal dialysis patients: a multi-center cross-sectional study.  


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

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



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


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



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

Microsoft Academic Search

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

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



Immunoprecipitation of the parathyroid hormone receptor  

SciTech Connect

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

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



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


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

Kimura, Shigemi; Yoshioka, Kowasi



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

PubMed Central

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

Kimura, Shigemi; Yoshioka, Kowasi



A prospective study of calciotropic hormones in pregnancy and post partum: Reciprocal changes in serum intact parathyroid hormone and 1,25-dihydroxyvitamin D  

Microsoft Academic Search

OBJECTIVE: The purpose of this study was to examine the hormones regulating calcium homeostasis longitudinally in pregnancy and post partum. STUDY DESIGN: Twenty-three women with normal pregnancies were studied in the second and third trimesters and post partum. At each time blood was analyzed for ionized calcium, vitamin D metabolites, and intact parathyroid hormone, and a 24-hour urine specimen was

Ellen W. Seely; Edward M. Brown; Derna M. DeMaggio; Dale K. Weldon; Steven W. Graves



Engineering a soluble parathyroid hormone GPCR mimetic.  


We designed and characterized a soluble mimic of the parathyroid hormone (PTH) receptor (PTH1R) that incorporates the N-terminus and third extracellular loop of PTH1R, important for ligand binding. The engineered receptor (PTH1R-NE3) was conceived to enable easy production and the use of standard biochemical and biophysical assays for the screening of competitive antagonists of PTH. We show that PTH1R-NE3 is folded, thermodynamically stable and selectively binds PTH. We also demonstrate the utility of our mimic by identifying a small molecule that competes with PTH in our PTH1R-NE3-based fluorescence polarization assay. Antagonists to PTH1R, a transmembrane protein belonging to the class B G-protein coupled receptor family, may provide new therapeutic options for calcium metabolism diseases like humoral hypercalcemia of malignancy. Proteins 2014; 82:1370-1375. © 2013 Wiley Periodicals, Inc. PMID:24375686

Audu, Christopher O; Plati, Jessica J; Pellegrini, Maria; Mierke, Dale F



Three-year follow-up of serum 25-hydroxyvitamin D, parathyroid hormone, and bone mineral density in nursing home residents who had received 12 months of daily bread fortification with 125 ?g of vitamin D3  

PubMed Central

Background We conducted a single-arm clinical trial in institutionalized seniors, on the effects of high-dose vitamin D3-fortified bread daily intake ( registration NCT00789503). Methods At 1 and 3 years after the dietary fortification was stopped, serum 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and bone mineral density were measured in 23 of the original study subjects, aged 60-82 years who had consumed bread buns (100 g) fortified with 320 mg elemental calcium and 125 ?g (5,000 IU) vitamin D3 daily for one year. Results At the end of the 1-year supplementation phase (receiving vitamin D3 fortified bread daily), mean (SD) serum 25(OH)D was 127.3?±?37.8 nmol/L (baseline for this follow-up). At 1-year follow-up, the serum 25(OH)D was 64.9?±?24.8 nmol/L (p?=?0.001, vs. baseline); and at 3-year follow-up it was 28.0?±?15.0 nmol/L (p?=?0.001 vs. baseline). Serum PTH was 18.8?±?15.6 pg/ml at baseline while at Year 3 it was 48.4?±?18.4 pg/ml (p?=?0.001 vs. baseline). Lumbar spine BMD did not change from baseline to Year 3. However, by Year 3, hip BMD had decreased (0.927?±?0.130 g/cm2 vs. 0.907?±?0.121 g/cm2, p?=?0.024). Conclusion Vitamin D nutritional status exhibits a long half-life in the body, and a true steady-state plateau may not even be reached 1 year after a discontinuation in dose. Furthermore, once the need for vitamin D has been established, based on a low baseline serum 25(OH)D concentrations, the appropriate action is to maintain corrective vitamin D supplementation over the long term. Trial registration Clinical trial registration number: NCT00789503



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

PubMed Central

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

Abdelgadir Adam, Mohamed; Untch, Brian R.



Cytochemical bioassay of parathyroid hormone in maternal and cord blood.  

PubMed Central

Parathyroid hormone and calcium were measured in plasma taken from pregnant women at term and from the umbilical veins of their infants at birth. Three assays were used to measure parathyroid hormone, a cytochemical bioassay of bioactivity and two immunoradiometric assays, one specific for the amino terminus, the other specific for the carboxy terminus of the parathyroid hormone molecule. Plasma calcium was significantly higher in the infants than in the mothers. Maternal parathyroid hormone bioactivity and the amino terminus were both slightly raised, but the carboxy terminus value was normal; these findings supported the view that late pregnancy is a time of mild physiological hyperparathyroidism. In the infants, the amino terminus was undetectable and the carboxy terminus was either undetectable or towards the lower end of the normal range: bioactivity of parathyroid hormone was considerably raised and was related to the gradient of calcium across the placenta. This suggests that the parathyroid glands are not suppressed during fetal life and that they may play an important part in the maintenance of high fetal plasma calcium concentrations.

Allgrove, J; Adami, S; Manning, R M; O'Riordan, J L



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: [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)



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.

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



Mid-molecule parathyroid hormone assay comparison.  


Parathyroid hormone (PTH) assays are becoming available to clinical chemistry laboratories for in-house use. We evaluated the clinical utility of two mid-molecule PTH assays in comparison to a sensitive but technically demanding component assay. A normal reference population, and an abnormal population including cases of primary and secondary hyperparathyroidism, hypoparathyroidism, and humoral hypercalcemia of malignancy were tested. PTH determinations with each assay system and total serum calcium determinations were done on all specimens. The Endocrine Metabolic Center (EMC) kit assay and the Immuno Nuclear Corp. (INC) kit assay demonstrated adequate standard curve reproducibility and precision for clinical use. With the aid of calcium determinations each assay performed well in the separation of abnormal patient groups, and in the separation of abnormal from normal PTH-calcium homeostasis. PTH values for the reference population differed among the three assays. The component assay and the EMC assay had a negative correlation with serum calcium, but the INC assay had a positive correlation with serum calcium. PMID:3955805

Ivie, W M; Orwoll, E S; McClung, M R; Kenny, T A; Swanson, J R



Regulation of parathyroid hormone synthesis in chronic renal failure in rats  

Microsoft Academic Search

Regulation of parathyroid hormone synthesis in chronic renal failure in rats. To clarify the mechanism of secondary hyperparathyroidism in chronic renal failure at the parathyroid hormone (PTH) synthesis level, we measured PTH messenger RNA (mRNA) levels in parathyroid glands in a rat model of chronic renal failure. Four weeks after 7\\/8 nephrectomy, hyperplasia of parathyroid glands was evident and serum

Masafumi Fukagawa; Shin-ya Kaname; Tetsuya Igarashi; Etsuro Ogata; Kiyoshi Kurokawa



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.



Functional parathyroid hormone receptors are present in an umbilical vein endothelial cell line.  


Acute parathyroid hormone exposure induces vascular smooth muscle relaxation. In contrast, continuous infusion of parathyroid hormone leads to vasoconstriction and an elevation of blood pressure. Despite the known effects of parathyroid hormone on vascular smooth muscle, possible direct effects on the vascular endothelium have not previously been investigated. Using a human umbilical vein endothelial cell line, we found that parathyroid hormone increased both intracellular calcium and cellular cAMP content in these endothelial cells. Furthermore, exposure of these cells to increasing concentrations of parathyroid hormone stimulated both [(3)H]thymidine incorporation and endothelin-1 secretion. Parathyroid hormone/parathyroid hormone-related peptide receptor mRNA could be detected at low levels in these cells. In summary, these data demonstrate that endothelium-derived cells contain functional parathyroid hormone receptors. The potential physiological role of these receptors remains to be determined. PMID:10950835

Isales, C M; Sumpio, B; Bollag, R J; Zhong, Q; Ding, K H; Du, W; Rodriguez-Commes, J; Lopez, R; Rosales, O R; Gasalla-Herraiz, J; McCarthy, R; Barrett, P Q



Use of parathyroid hormone in hypoparathyroidism.  


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

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



Ontogeny of parathyroid hormone-related protein in the ovine parathyroid gland.  


PTH-related protein (PTHrP) has been implicated in calcium regulation during fetal life. In this study the ontogeny of PTHrP was examined in ovine parathyroid glands. Immunohistochemical techniques, Western blot analysis, and a RIA with antisera raised against synthetic fragments of human (h) PTHrP (i.e. 1-34, 1-40, 50-69, and 107-141) were used to detect the presence of immunoreactive PTHrP in parathyroid glands from fetal and neonatal lambs and maternal ewes. Positive immunostaining for PTHrP was observed in fetal (from 116 days of gestation) and lamb (up to 180 days post birth) but not maternal parathyroid glands with the PTHrP(50-69) antiserum. Fetal and lamb parathyroid glands consisted entirely of one cell type in which PTHrP immunoreactivity to PTHrP(50-69) antiserum was found. In contrast, immunoreactivity to PTHrP could not be detected in sections of fetal, lamb, or maternal parathyroid glands with antisera raised against PTHrP(1-34) or PTHrP(107-141). However, PTHrP immunoreactivity in urea/acid extracts of newborn lamb parathyroid glands could be detected by Western blot analysis and RIA with antisera raised against the N-terminal portion of PTHrP. Western blot analysis with the PTHrP(1-34) antisera revealed that urea/acid extracts of newborn lamb parathyroid glands contained a substance with a mol wt of 14.4K, which corresponded in size to that of hPTHrP(1-84). Newborn lamb parathyroid glands contained 0.35 ng PTHrP/micrograms extract, whereas maternal parathyroid glands contained only 0.035 ng PTHrP/micrograms extract when tested in a RIA employing recombinant hPTHrP(1-84) as standard and an antibody raised against hPTHrP(1-40). The detection of immunoreactive PTHrP in the developing ovine parathyroid gland provides further evidence to support the suggestion that PTHrP produced in the parathyroid gland is involved in the normal hormonal regulation of calcium metabolism in the mammalian fetus and neonate. PMID:1855473

MacIsaac, R J; Caple, I W; Danks, J A; Diefenbach-Jagger, H; Grill, V; Moseley, J M; Southby, J; Martin, T J



Parathyroid hormone and physical exercise: a brief review.  


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

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



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))



The Role of Parathyroid Hormone in the Management of Osteoporosis  

Microsoft Academic Search

It has been over 2 years since parathyroid hormone (PTH 1–34) was approved in the US and Europe for the treatment of osteoporosis in postmenopausal women and men. Clinical experience with this peptide has enhanced confidence in its use and its application in specific clinical scenarios. There is no doubt that PTH 1–34 is safe and effective in reducing spine

Clifford J. Rosen



Role of Parathyroid Hormone as a Uremic Toxin.  

National Technical Information Service (NTIS)

The final report summarizes the work completed during the period between 7/22/79 and 9/30/81. Five areas of investigation on the effect of parathyroid hormone (PTH) on various organ systems are described. The results demonstrate a wide variety of extraske...

S. G. Massry



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

PubMed Central

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

Hjelmesaeth, J?ran; Hofs?, Dag; Aasheim, Erlend T; Jenssen, Trond; Moan, Johan; Hager, Helle; R?islien, Jo; Bollerslev, Jens



Parathyroid biopsy  


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


Immunoheterogeneity of Parathyroid Hormone in Venous Effluent Serum from Hyperfunctioning Parathyroid Glands  

PubMed Central

The immunoreactive parathyroid hormone (iPTH) in the plasma of hyperparathyroid man consists largely of carboxyl (COOH)-terminal fragments of the hormone. Although these fragments have been thought to arise principally or solely from peripheral metabolism of intact human PTH {hPTH(1-84)} secreted from the parathyroid gland, there is disagreement about the source of iPTH fragments in vivo. To reexamine this question, we fractionated peripheral and thyroid or parathyroid venous effluent sera from four patients with primary hyperparathyroidism using a high-resolution gel filtration system (Bio-Gel P-150 columns run by reverse flow). The column effluents were analyzed using two PTH radioimmunoassays, one directed toward the amino(NH2)-terminal region of the molecule, the other toward the COOH-terminal region. In all four thyroid or parathyroid venous effluent sera studied, iPTH was 9-180 times higher than in peripheral serum from the same patient; after fractionation, hPTH(1-84) accounted for only a portion of the total iPTH (35-55% with the assay directed toward the COOH-terminal region of hPTH, >90% with the NH2-terminal directed assay.) The remaining iPTH eluted from Bio-Gel P-150 after hPTH(1-84) as NH2-or COOH-terminal hPTH fragments. These results suggest that parathyroid tumors secrete large quantities of hPTH fragments. Based on estimates of their molar concentrations in serum, tumor-secreted COOH-terminal hPTH fragments could account for most of these peptides in peripheral serum if their survival times were, as estimated by several other workers, 5-10 times that of hPTH(1-84). We conclude that, in contrast to published information, secretory products of hyperfunctioning parathyroid tissue are probably a major source of serum PTH immunoheterogeneity.

Flueck, James A.; Di Bella, Francis P.; Edis, Anthony J.; Kehrwald, Jean M.; Arnaud, Claude D.



Immunoheterogeneity of parathyroid hormone in venous effluent serum from hyperfunctioning parathyroid glands.  


The immunoreactive parathyroid hormone (iPTH) in the plasma of hyperparathyroid man consists largely of carboxyl (COOH)-terminal fragments of the hormone. Although these fragments have been thought to arise principally or solely from peripheral metabolism of intact human PTH {hPTH(1-84)} secreted from the parathyroid gland, there is disagreement about the source of iPTH fragments in vivo. To reexamine this question, we fractionated peripheral and thyroid or parathyroid venous effluent sera from four patients with primary hyperparathyroidism using a high-resolution gel filtration system (Bio-Gel P-150 columns run by reverse flow). The column effluents were analyzed using two PTH radioimmunoassays, one directed toward the amino(NH(2))-terminal region of the molecule, the other toward the COOH-terminal region. In all four thyroid or parathyroid venous effluent sera studied, iPTH was 9-180 times higher than in peripheral serum from the same patient; after fractionation, hPTH(1-84) accounted for only a portion of the total iPTH (35-55% with the assay directed toward the COOH-terminal region of hPTH, >90% with the NH(2)-terminal directed assay.) The remaining iPTH eluted from Bio-Gel P-150 after hPTH(1-84) as NH(2)-or COOH-terminal hPTH fragments. These results suggest that parathyroid tumors secrete large quantities of hPTH fragments. Based on estimates of their molar concentrations in serum, tumor-secreted COOH-terminal hPTH fragments could account for most of these peptides in peripheral serum if their survival times were, as estimated by several other workers, 5-10 times that of hPTH(1-84). We conclude that, in contrast to published information, secretory products of hyperfunctioning parathyroid tissue are probably a major source of serum PTH immunoheterogeneity. PMID:915003

Flueck, J A; Di Bella, F P; Edis, A J; Kehrwald, J M; Arnaud, C D



Parathyroid Hormone Mediates Hematopoietic Cell Expansion through Interleukin6  

Microsoft Academic Search

Parathyroid hormone (PTH) stimulates hematopoietic cells through mechanisms of action that remain elusive. Interleukin-6 (IL-6) is upregulated by PTH and stimulates hematopoiesis. The purpose of this investigation was to identify actions of PTH and IL-6 in hematopoietic cell expansion. Bone marrow cultures from C57B6 mice were treated with fms-like tyrosine kinase-3 ligand (Flt-3L), PTH, Flt-3L plus PTH, or vehicle control.

Flavia Q. Pirih; Megan N. Michalski; Sun W. Cho; Amy J. Koh; Janice E. Berry; Eduardo Ghaname; Pachiyappan Kamarajan; Edith Bonnelye; Charles W. Ross; Yvonne L. Kapila; Pierre Jurdic; Laurie K. McCauley; Derya Unutmaz



Parathyroid hormone-related protein and calcium phosphate metabolism  

Microsoft Academic Search

There is marked homology between the parathyroid hormone (PTH) and PTH-related protein (PTHrP) molecules at the amino terminal but the rest of the molecules are quite different, providing immunologically distinct peptides. However, they interact with the same receptor. Thus, PTHrP mediates biological actions reminiscent of PTH. PTHrP gene is a single copy gene, producting one to three mRNA transcripts through

F. Law; S. Ferrari; R. Rizzoli; J.-P. Bonjour



Large Scale Screening Programme for Selection of Antisera for Radioimmunoassay of Human Parathyroid Hormone  

Microsoft Academic Search

A large-scale, three-phase screening programme has been devised for the rapid selection of antisera which might be of potential use in clinical radioimmunoassays for human parathyroid hormone. A total of 122 sera from 169 guinea pigs and 6 rabbits immunized with bovine parathyroid hormone, and 12 guinea pigs immunized with human parathyroid hormone were assessed relative to reference antisera. Pre-determined

Joan M. Zanelli; B. Rafferty; B. Apostolou; G. Court; B. A. L. Hurn



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.

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



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

PubMed Central

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 ?-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.



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

SciTech Connect

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

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



Measurement of parathyroid hormone-related protein in extracts of fetal parathyroid glands and placental membranes.  


A radioimmunoassay based on an antiserum to human parathyroid hormone-related protein PTHrP(1-16) was used with PTHrP(1-34) standard to measure the concentration of immunoreactive PTHrP in extracts of fetal parathyroid glands from lambs and calves and also placental membranes obtained from several species, including man. Dilution curves from these sources were parallel to those obtained for PTHrP(1-34) standard. It was demonstrated that this parallelism was not the result of tracer damage caused by enzymic activity in the tissue extracts. Extracts of human placental membranes were subjected to high-pressure liquid chromatography with a linear acetonitrile gradient. Co-elution of cytochemical biological activity with 125I-labelled PTHrP(1-34) was noted. These results provide further evidence for both the fetal parathyroid glands and the placenta containing material resembling PTHrP which may be responsible for sustaining the activity of the placental calcium pump which maintains the fetus hypercalcaemic relative to its mother. PMID:2313219

Abbas, S K; Pickard, D W; Illingworth, D; Storer, J; Purdie, D W; Moniz, C; Dixit, M; Caple, I W; Ebeling, P R; Rodda, C P



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



Calcitonin, an important factor in the calcemic response to parathyroid hormone in the rat  

Microsoft Academic Search

Calcitonin, an important factor in the calcemic response to parathyroid hormone in the rat. The role of calcitonin on the calcemic response to parathyroid hormone (PTH) in renal failure has not been evaluated previously. Often animal studies evaluating the calcemic response to PTH in renal failure are performed in thyroparathyroidectomized (TPTX) animals, and thus eliminate any potential physiologic effect of

Mariano Rodriguez; Arnold J Felsenfeld; Armando Torres; Lee Pederson; Francisco Llach



Predicting Parathyroid Hormone Levels in Diabetic Hemodialysis Patients Using Neural Networks  

Microsoft Academic Search

Parathyroid Hormone (PTH) is an important biochemical indicator for the medical condition of osteodystrophy in patients on hemodialysis. Prior studies have been conducted to classify hemodialysis patients based on their PTH level, using neural networks. This paper introduces the possibilities of predicting parathyroid hormone levels in the more specific case of diabetic patients. The performance of two different neural network

Jesse Bumanlag; Anahita Zarei; Pourya Ghazi; Sheela Kapre; Lawrence Frank



Parathyroid hormone and eggshell calcification in Japanese quail.  


The effect of parathyroid hormone (PTH) on egg-shell calcification has been investigated in egg-laying Japanese quail. Lilly parathyroid extract (PTE) when injected into quail within 2-6 h of oviposition caused a significantly increased deposition of a chronic 45Ca label into the sequential egg-shell compared with the previous egg in the clutch, indicating increased mobilization of bone Ca and its subsequent incorporation into the egg-shell. At the same time egg-shell weight/unit area and egg-shell Ca/unit area were significantly decreased. Parathyroid extract injected 12-16 after oviposition had none of these effects. Purified PTH also caused a significant decrease in egg-shell weight/unit area if injected within 2-6 h of oviposition. This result indicated an action of PTH either directly or indirectly on the avian oviduct limiting egg-shell calcification. The loss of responses in the 12-16 h treated birds may reflect high endogenous PTH levels with subsequent saturation of target organ receptors. PMID:1010971

Dacke, C G



Heterogeneity of Parathyroid Hormone. CLINICAL AND PHYSIOLOGIC IMPLICATIONS  

PubMed Central

When immunoreactive human parathyroid hormone (hPTH), extracted by three different solvents (20% acetone in 1% acetic acid, 8 M urea, or normal saline) from parathyroid glandular tissue was subjected to Sephadex G-100 gel filtration and immunoassay using two different antisera (273 and C-329), four distinct fractions were observed. The first (I), a void volume peak, was detected by both antisera with similar immunoreactivity, as was a second (II), which had the elution and sedimentation properties of highly purified bovine parathyroid hormone (bPTH); a third (III) eluted between [125I]growth hormone and [125I]insulin, sedimented with the velocity of a molecule of approximately 6,000 mol wt, and was detected primarily by antiserum 273; a final fraction (IV), detected primarily by C-329, eluted just prior to [125I]insulin. The elution profiles of the acetone-acetic acid and 8 M urea extracts were similar and contained fraction II as their major component. In saline extracts, however, fraction III predominated. Three fractions, having gel filtration and immunologic characteristics similar to fractions II, III, and IV, respectively, of saline glandular extracts, were detected in the plasma of patients with both primary (adenomatous or carcinomatous) and secondary hyperparathyroidism. The predominant component in every plasma was the intermediate fraction that, like III, was detected primarily by antiserum 273, while the least abundant form was consistently the final fraction, detected primarily by antiserum C-329. The first fraction, like II, was detected with about equal potency by both antisera and had an elution volume on Sephadex corresponding to that of intact bPTH. It bore a reciprocal relationship to serum calcium and disappeared from the plasma of a uremic patient during calcium infusion or following parathyroidectomy with a half-time of no more than 20 min. This component therefore probably represents biologically active hormone. The intermediate and final fractions had turnover times in the plasma of a uremic patient more than 100 times greater than the active form, remained elevated even in the presence of post-parathyroidectomy hypoparathyroidism in this patient and were presumed to be biologically inactive. The ratio of biologically inactive fragments to the active form was greater in secondary hyperparathyroidism. The evidence presented favors a glandular origin for the fragments. Comparison of hormonal assays with the two antisera reveals a striking advantage in the preoperative diagnosis of primary hyperparathyroidism with antiserum 273 that is due to the enhanced sensitivity occasioned by its detection of a biologically inactive as well as the biologically active hormonal form. Images

Silverman, Robert; Yalow, Rosalyn S.



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.



Vascular effects of parathyroid hormone and parathyroid hormone-related protein in the split hydronephrotic rat kidney.  

PubMed Central

1. The effects of locally applied parathyroid hormone-related protein (PTHRP), a putative autocrine/paracrine hormone, on vascular diameters and glomerular blood flow (GBF) in the split hydronephrotic rat kidney were studied. As PTHRP interacts with parathyroid hormone (PTH) receptors in all tissues tested so far, the effects of PTHRP were compared with those of PTH. 2. Preglomerular vessels dilated in a concentration- and time-dependent manner that was almost identical for PTH and PTHRP. A significant preglomerular vasodilation (5-17%) occurred at a threshold concentration of 10(-10) mol l-1 PTH or PTHRP, which raised GBF by 20 +/- 2 and 31 +/- 4%, respectively (means +/- S.E.M., n = 6). PTH or PTHRP (10(-7) mol l-1) increased preglomerular diameters (11-36%) and GBF (60 +/- 10 and 70 +/- 8%, respectively) to near maximum. The most prominent dilatation was located at the interlobular artery and at the proximal afferent arteriole. 3. Efferent arterioles were not affected by either PTH or PTHRP. 4. Estimated concentrations of half-maximal response (EC50) for preglomerular vasodilatation and GBF increase were in the nanomolar to subnanomolar range. 5. After inhibition of angiotensin I-converting enzyme by 2 x 10(-6) mol kg-1 quinapril I.V. (n = 6), 10(-8) mol l-1 PTHRP dilated preglomerular vessels and efferent arterioles (9 +/- 1% proximal and 6 +/- 1% distal). 6. We conclude that the renal vasculature of the hydronephrotic kidney is highly sensitive to vasodilatation by PTH and PTHRP, which, in addition, may constrict efferent arterioles by stimulating renin release.(ABSTRACT TRUNCATED AT 250 WORDS)

Endlich, K; Massfelder, T; Helwig, J J; Steinhausen, M



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.



A different interaction between parathyroid hormone, calcitriol and serum aluminum in chronic kidney disease; a pilot study  

Microsoft Academic Search

Background\\/Aims  Aluminum (Al) is an ingredient of a variety of foodstuffs and medications as well as of domestic water supplies. The patients\\u000a with chronic kidney disease (CKD) are more susceptible to bone toxicity of Al. The aim of the study was to investigate the\\u000a interactions between serum Al, parathyroid hormone (PTH) and active vitamin-D in CKD.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  A total of 10 pediatric

Fatih Mehmet Azik; Mesiha Ekim; Onur Sakallioglu; Ahmet Aydin



Coordinated control of renal Ca2+ transport proteins by parathyroid hormone  

Microsoft Academic Search

Coordinated control of renal Ca2+ transport proteins by parathyroid hormone.BackgroundThe kidney is one of the affected organs involved in the clinical symptoms of parathyroid hormone (PTH)-related disorders, like primary hyperparathyroidism and familial hypocalciuric hypercalcemia. The molecular mechanism(s) underlying alterations in renal Ca2+ handling in these disorders is poorly understood.MethodsParathyroidectomized and PTH-supplemented rats and mice infused with the calcimimetic compound NPS




The Neuroendocrine Functions of the Parathyroid Hormone 2 Receptor  

PubMed Central

The G-protein coupled parathyroid hormone 2 receptor (PTH2R) is concentrated in endocrine and limbic regions in the forebrain. Its endogenous ligand, tuberoinfundibular peptide of 39 residues (TIP39), is synthesized in only two brain regions, within the posterior thalamus and the lateral pons. TIP39-expressing neurons have a widespread projection pattern, which matches the PTH2R distribution in the brain. Neuroendocrine centers including the preoptic area, the periventricular, paraventricular, and arcuate nuclei contain the highest density of PTH2R-positive networks. The administration of TIP39 and an antagonist of the PTH2R as well as the investigation of mice that lack functional TIP39 and PTH2R revealed the involvement of the PTH2R in a variety of neural and neuroendocrine functions. TIP39 acting via the PTH2R modulates several aspects of the stress response. It evokes corticosterone release by activating corticotropin-releasing hormone-containing neurons in the hypothalamic paraventricular nucleus. Block of TIP39 signaling elevates the anxiety state of animals and their fear response, and increases stress-induced analgesia. TIP39 has also been suggested to affect the release of additional pituitary hormones including arginine-vasopressin and growth hormone. A role of the TIP39-PTH2R system in thermoregulation was also identified. TIP39 may play a role in maintaining body temperature in a cold environment via descending excitatory pathways from the preoptic area. Anatomical and functional studies also implicated the TIP39-PTH2R system in nociceptive information processing. Finally, TIP39 induced in postpartum dams may play a role in the release of prolactin during lactation. Potential mechanisms leading to the activation of TIP39 neurons and how they influence the neuroendocrine system are also described. The unique TIP39-PTH2R neuromodulator system provides the possibility for developing drugs with a novel mechanism of action to control neuroendocrine disorders.

Dobolyi, Arpad; Dimitrov, Eugene; Palkovits, Miklos; Usdin, Ted B.



The neuroendocrine functions of the parathyroid hormone 2 receptor.  


The G-protein coupled parathyroid hormone 2 receptor (PTH2R) is concentrated in endocrine and limbic regions in the forebrain. Its endogenous ligand, tuberoinfundibular peptide of 39 residues (TIP39), is synthesized in only two brain regions, within the posterior thalamus and the lateral pons. TIP39-expressing neurons have a widespread projection pattern, which matches the PTH2R distribution in the brain. Neuroendocrine centers including the preoptic area, the periventricular, paraventricular, and arcuate nuclei contain the highest density of PTH2R-positive networks. The administration of TIP39 and an antagonist of the PTH2R as well as the investigation of mice that lack functional TIP39 and PTH2R revealed the involvement of the PTH2R in a variety of neural and neuroendocrine functions. TIP39 acting via the PTH2R modulates several aspects of the stress response. It evokes corticosterone release by activating corticotropin-releasing hormone-containing neurons in the hypothalamic paraventricular nucleus. Block of TIP39 signaling elevates the anxiety state of animals and their fear response, and increases stress-induced analgesia. TIP39 has also been suggested to affect the release of additional pituitary hormones including arginine-vasopressin and growth hormone. A role of the TIP39-PTH2R system in thermoregulation was also identified. TIP39 may play a role in maintaining body temperature in a cold environment via descending excitatory pathways from the preoptic area. Anatomical and functional studies also implicated the TIP39-PTH2R system in nociceptive information processing. Finally, TIP39 induced in postpartum dams may play a role in the release of prolactin during lactation. Potential mechanisms leading to the activation of TIP39 neurons and how they influence the neuroendocrine system are also described. The unique TIP39-PTH2R neuromodulator system provides the possibility for developing drugs with a novel mechanism of action to control neuroendocrine disorders. PMID:23060860

Dobolyi, Arpád; Dimitrov, Eugene; Palkovits, Miklós; Usdin, Ted B



Parathyroid cancer  


... tends to produce a very high amount of parathyroid hormone (PTH). Tests for this hormone may include: Blood ... may be used to correct hypercalcemia due to parathyroid cancer: A drug ... called calcitonin that helps control calcium level Drugs ...


[Distribution and function of a new hormone: parathyroid hormone-related peptide (PTHrP)].  


Several research groups have identified a "parathyroid hormone related peptide" (PTHrP) in tumors of patients presenting with the hypercalcemia of malignancy. The N-terminal domain of this peptide has a high degree of homology with that of the parathyroid hormone (PTH) and shares the PTH biological activities. PTHrP has later been identified in several foetal and adult normal tissues: for instance, it is expressed and secreted by foetal parathyroid glands, and it plays an important role in placental calcium transport; it is also expressed in the uterus of pregnant rats; there it could have a paracrine action on myometer relaxation. We have shown that PTHrP is present in and released in culture by foetal rat long bones. The mRNA of PTHrP is expressed in the periosteal cells of these foetal bones. The local expression and secretion of PTHrP in bone suggests that this new peptide could have a local role in the regulation of bone remodeling and development. PMID:7987287

Bergmann, P; Nijs-De Wolf, N; Karmali, R; Pepersack, T; Corvilain, J



The Role of Parathyroid Hormone\\/Parathyroid Hormone-Related Protein Receptor (PTH\\/PTHrP-R) Regulation in the Skeletal Resistance of Renal Osteodystrophy  

Microsoft Academic Search

Resistance to the effects of parathyroid hormone occurs in a variety of situations. It has been shown to occur in renal failure and is considered to be important in the pathogenesis of secondary hyperparathyroidism and may play a role in adynamic bone disease. The precise mechanism of resistance is unclear but altered regulation of the PTH\\/PTHrP-R or a disturbance of

R. Gokal



Catabolic and anabolic actions of parathyroid hormone on the skeleton.  


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 amino-terminal 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



Parathyroid hormone impairs extrarenal potassium tolerance in the rat  

SciTech Connect

The effect of parathyroid hormone (PTH) on the extrarenal disposition of an acute potassium load was examined in acutely nephrectomized rats infused with KCl alone or in combination with PTH, with serial monitoring of plasma potassium every 10 min. The rise in plasma potassium concentration ({Delta}PK) in the PTH group was higher than control. PTH was then administered along with KCl to two groups of nephrectomized and acutely thyroparathyroidectomized (TPTX) rats in doses of 1 and 0.25 U {center dot} kg{sup {minus}1} {center dot} min{sup {minus}1} for 90 min. {Delta}PK with PTH in both groups was higher than TPTX control. The two higher doses of PTH resulted in a decrease in mean arterial pressure from their respective controls. A similar reduction in arterial pressure in three groups of nephrectomized rats by administration of hydralazine or nitroprusside or by acute blood loss did not change {Delta}PK subsequent to potassium infusion from that in control rats. Furthermore, the lowest dose of PTH did not lower arterial pressure from its respective control. Therefore, hypotension is not a cause for the PTH-induced potassium intolerance. Serum levels of insulin, aldosterone, catecholamines, calcium, plasma HCO{sub 3} concentration, and pH were not different in PTH-infused vs. respective control rats. These data suggest that PTH impairs extrarenal potassium disposal in the rat. The effect of PTH may relate to enhanced calcium entry into cells.

Sugarman, A.; Kahn, T. (Veterans Administration Medical Center, Bronx, NY (USA) City Univ. of New York, NY (USA))



Parathyroid hormone-related protein in teleost fish.  


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



Elevation of Parathyroid Hormone Levels in Atrial Fibrillation  

PubMed Central

Objective PTH influences atrial fibrillation (AF) risk factors and pathways involved in AF. We therefore sought to determine if PTH levels are altered in patients with AF. Background In addition to the traditional role of parathyroid hormone (PTH) as a regulator of calcium homeostasis, PTH also acts as a cardiac hormone, vasodilatory substance, and regulator of smooth muscle proliferation. Methods We compared plasma PTH levels in subjects with early-onset AF (n=230; 144 with lone AF and 86 with AF and hypertension), and control subjects (n=150). Subjects with structural heart disease were excluded. Plasma PTH levels were determined using a commercially available immunoassay. Results PTH levels were higher in subjects with early-onset AF versus controls (56 versus 50 pg/ml, p=0.01), and there was a stepwise increase in PTH levels from controls, to lone AF and AF and hypertension (50, 54 and 59 pg/ml, p=0.03). PTH levels were higher in permanent AF compared to paroxysmal AF (61 versus 55 pg/ml, p=0.03). PTH levels were higher in subjects with AF compared to sinus rhythm at the time of blood draw (64 versus 54 pg/ml, p=0.001). In a multivariable analysis, each mm increase in left atrial size was associated with a 0.005 (±0.002) pg/ml increase in log(PTH) levels (p=0.047). Conclusions We demonstrate that PTH levels are higher in AF subjects, most prominently in subjects with hypertension and in AF at blood sampling. These data suggest that both the rhythm itself and hypertension, as a concomitant condition, may influence the relation between PTH and AF.

Rienstra, Michiel; Lubitz, Steven A.; Zhang, Michael L.; Cooper, Rebecca R.; Ellinor, Patrick T.



Nmp4/CIZ closes the parathyroid hormone anabolic window.  


Chronic degenerative diseases are increasing with the aging U.S. population. One consequence of this phenomenon is the need for long-term osteoporosis therapies. Parathyroid hormone (PTH), the only FDA-approved treatment that adds bone to the aged skeleton, loses its potency within two years of initial treatment but the mechanism regulating its limited "anabolic window" is unknown. We have discovered that disabling the nucleocytoplasmic shuttling transcription factor nuclear matrix protein 4/cas interacting zinc finger protein (Nmp4/CIZ) in mice extends the PTH bone-forming capacity. Nmp4 was discovered during our search for nuclear matrix transcription factors that couple this hormone's impact on osteoblast cytoskeletal and nuclear organization with its anabolic capacity. CIZ was independently discovered as a protein that associates with the focal adhesion-associated mechanosensor p130Cas. The Nmp4/CIZ-knockout (KO) skeletal phenotype exhibits a modestly enhanced bone mineral density but manifests an exaggerated response to both PTH and to BMP2 and is resistant to disuse-induced bone loss. The cellular basis of the global Nmp4/CIZ-KO skeletal phenotype remains to be elucidated but may involve an expansion of the bone marrow osteoprogenitor population along with modestly enhanced osteoblast and osteoclast activities supporting anabolic bone turnover. As a shuttling Cys(2)His(2) zinc finger protein, Nmp4/CIZ acts as a repressive transcription factor perhaps associated with epigenetic remodeling complexes, but the functional significance of its interaction with p130Cas is not known. Despite numerous remaining questions, Nmp4/CIZ provides insights into how the anabolic window is regulated, and itself may provide an adjuvant therapy target for the treatment of osteoporosis by extending PTH anabolic efficacy. PMID:23140162

Bidwell, Joseph P; Childress, Paul; Alvarez, Marta B; Hood, Mark; He, Yongzheng; Pavalko, Fredrick M; Kacena, Melissa A; Yang, Feng-Chun



New Point-of-care Intraoperative Parathyroid Hormone Assay for Intraoperative Guidance in Parathyroidectomy  

Microsoft Academic Search

  \\u000a The use of the intraoperative parathyroid\\u000a hormone assay (QPTH) to guide a limited parathyroidectomy in\\u000a patients with sporadic primary hyperparathyroidism (SPHPT) is well\\u000a established. The advantage of having this assay performed in the\\u000a operating room is immediate feedback for (1) confirming the complete\\u000a excision of all hyperfunctioning parathyroid(s); (2) differential\\u000a jugular venous sampling for localization; and (3) diagnosing suspected

Denise M. Carneiro; George L. Irvin III



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

PubMed Central

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

MacDonald, P N; Ritter, C; Brown, A J; Slatopolsky, E



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

PubMed Central

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

Daugaard, H.; Elmengaard, B.; Andreassen, T. T.; Baas, J.; Bechtold, J. E.; S?balle, K.



Pathogenesis of Hypocalcemia in Primary Hypomagnesemia: Normal End-Organ Responsiveness to Parathyroid Hormone, Impaired Parathyroid Gland Function  

PubMed Central

Hypocalcemia is a frequent feature of hypomagnesemia in man and several other species. To elucidate the cause of this hypocalcemia, we have studied a child with primary hypomagnesemia and secondary hypocalcemia during magnesium supplementation when he was normomagnesemic and normocalcemic and after magnesium restriction for 16 days when he quickly became hypomagnesemic (0.5 meq/liter) and hypocalcemic (3.4 meq/liter) and had positive Chvostek's and Trousseau's signs. Whether in the normomagnesemic or hypomagnesemic state, intravenous bovine parathyroid extract (PTE) 8 U. S. P. U/kg promptly caused transient increases in the urinary phosphate excretion, renal phosphate clearance and cyclic AMP excretion. The magnitudes of these responses were similar in the two states, and similar to those observed in a hypoparathyroid patient. When the patient was hypomagnesemic and hypocalcemic, intramuscular PTE, 8 U/kg at 8-h intervals for four doses promptly caused hypercalcemia. The findings indicate that the end-organs were responsive to parathyroid hormone. The concentrations of serum parathyroid hormone (PTH) were normal in the normomagnesemic state ranging from 0.15 ng/ml to 0.40 ng/ml. Serum PTH did not increase in the hypomagnesemic state in spite of hypocalcemia. Indeed, PTH became unmeasurable in four consecutive samples at the end of the period of magnesium restriction. The concentrations of serum calcitonin remained unmeasurable (< 0.10 ng/ml) throughout the study, implying that excess calcitonin was not the cause of hypocalcemia in magnesium depletion. The findings in this study support our thesis that magnesium depletion causes impaired synthesis or secretion of parathyroid hormone. This impairment would account for the hypocalcemia observed in the hypomagnesemic state. Images

Suh, Se Mo; Tashjian, Armen H.; Matsuo, Nobutake; Parkinson, David K.; Fraser, Donald



The secretory response of parathyroid hormone to acute hypocalcemia in vivo is independent of parathyroid glandular sodium\\/potassium-ATPase activity  

Microsoft Academic Search

The involvement of sodium\\/potassium-ATPase in regulating parathyroid hormone (PTH) secretion is inferred from in vitro studies. Recently, the ?-klotho-dependent rapid recruitment of this ATPase to the parathyroid cell plasma membrane in response to low extracellular calcium ion was suggested to be linked to increased hormone secretion. In this study, we used an in vivo rat model to determine the importance

Giedre Martuseviciene; Jacob Hofman-Bang; Torben Clausen; Klaus Olgaard; Ewa Lewin



Parathyroid Disorders  


... glands are completely different. The parathyroid glands make parathyroid hormone (PTH), which helps your body keep the right balance of calcium and phosphorous. If your parathyroid glands make too much or too little hormone, it disrupts this balance. If they secrete extra ...


Serum Parathyroid Hormone Levels Predict Falls in Older Diabetic Adults  

PubMed Central

Objectives To examine the association between serum parathyroid hormone (PTH) levels and incident falls in older diabetic adults. Design Longitudinal analysis of incident falls over 1 year in a sub-study of diabetic participants in the Health, Aging and Body Composition study. Setting Pittsburgh, PA, and Memphis, TN. Participants Well-functioning, community-dwelling black and white adults aged 70-79 with diabetes (n = 472). Measurements Measured baseline serum PTH. Self-report of falls over the subsequent 12 months. Baseline physical performance and self-reported demographic, behavioral, and health status measures including kidney function, chronic conditions and medication use. Results 30.3% of participants reported falling over one year of follow-up. The mean ± SD baseline serum PTH was 53.5 ± 30.0 pg/mL in non-fallers and 62.6 ± 46.2 pg/mL in fallers (p = 0.01). For every 1 SD (36 pg/mL) increment in baseline serum PTH, there was approximately a 30% increased likelihood of reporting a fall in the subsequent year after adjusting for age, gender, race, field center, alcohol consumption, BMI, physical activity, and winter/spring season (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.06-1.59). Further adjustment for kidney function, chronic conditions, medication and supplement use, and physical performance attenuated the association slightly (OR (95% CI): 1.26 (1.01-1.58)). A trend remained after additional adjustment for reported falls in the previous year. Conclusion Higher serum PTH was associated with incident falls among older, well-functioning diabetic men and women. Further investigation aimed at understanding the underlying mechanism for the association between serum PTH and falls is needed.

Houston, Denise K.; Schwartz, Ann V.; Cauley, Jane A.; Tylavsky, Frances A.; Simonsick, Eleanor M.; Harris, Tamara B.; de Rekeneire, Nathalie; Schwartz, Gary G.; Kritchevsky, Stephen B.



The relationship between apelin and parathyroid hormone in hemodialysis patients.  


Both apelin and parathyroid hormone (PTH) are endogenous ligands for G-protein-coupled receptors. Apelin acts as a mitogenic agent for osteoblasts, and metabolic bone abnormalities are frequently seen in hemodialysis (HD) patients because of hyperparathyroidism. The aim of this study was to analyze plasma apelin levels in HD patients and to determine whether they are related to PTH concentrations. A total of 23 HD patients [15 men and 8 women, with a mean (SD) age of 54.2 (4.4) years and a mean body mass index (BMI) of 25.0 (4.1) kg/m(2)] were studied and compared with 15 healthy subjects [6 men and 9 women, with a mean (SD) age of 51.3 (13.6) years and a BMI of 27.0 (4.3) kg/m(2)]. Plasma apelin-36 was measured using an enzyme immunometric assay method and PTH was measured by ELISA. There was no significant difference in apelin levels between the patients [0.80 (0.6) ng/mL] and the healthy subjects [0.83 (0.23) ng/mL]. There was a positive correlation between apelin and PTH (r = 0.66, p = 0.0001). The patients with PTH >300 pg/mL had significantly higher plasma apelin levels [1.17 (0.7) ng/mL] compared with the patients with PTH <300 pg/mL [0.50 (0.15) ng/mL] (p = 0.003). In conclusion, HD patients with secondary hyperparathyroidism have high plasma apelin levels, which suggest that apelin may protect bone in HD patients by acting as an osteoblastic factor. PMID:22780711

Mafra, Denise; Lobo, Julie C; Farage, Najla E; Stockler-Pinto, Milena B; Leal, Viviane O; Calixto, Antonio; Geloneze, Bruno



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.

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



Parathyroid hormone, prolactin, and function of the pituitary-gonadal axis in male patients with acute renal failure  

Microsoft Academic Search

Parathyroid hormone, prolactin, and function of the pituitary-gonadal axis in male patients with acute renal failure. In 26 patients with acute renal failure (ARF), plasma levels of lutropin (LH), folitropin (FSH), prolactin, testosterone, estradiol, and parathyroid hormone (PTH) were studied at the anuric\\/oliguric (AOP) and polyuric phase. Significantly elevated levels of LH, FSH, and prolactin were found during the AOP.

Franciszek Kokot; Zofia Mleczko; Andrzej Pazera



Stages of Parathyroid Cancer  


... near the thyroid gland . The parathyroid glands make parathyroid hormone (PTH or parathormone). PTH helps the body use ... The patient's symptoms, blood levels of calcium and parathyroid hormone , and characteristics of the tumor are also used ...


The role of parathyroid hormone-related protein in calcium homeostasis in the fetal pig.  


The concentrations of plasma parathyroid hormone-like bioactivity and parathyroid hormone-related protein (1-86) (PTHrP) immunoreactivity were both higher in fetal pigs than in their mothers during the last 3 weeks of gestation. Both activities changed inversely with alterations in the plasma ionized calcium concentration. The data suggest that PTHrP may have a role in calcium homeostasis in the fetal pig, similar to its postulated role in sheep in the stimulation of calcium transport across the placenta. PMID:7946281

Abbas, S K; Ratcliffe, W A; Moniz, C; Dixit, M; Caple, I W; Silver, M; Fowden, A; Care, A D



Autoradiographic studies with 3 H 1,25 (OH) 2 vitamin D 3 and 3 H 25 (OH) vitamin D 3 in rat parathyroid glands  

Microsoft Academic Search

After injection of radiolabeled 1,25 (OH)2 vitamin D3, nuclear concentration of radioactivity is observed in parenchymal cells of the parathyroid gland in pregnant, adult male, and 10-day male neonatal rats. In competition studies with unlabeled 1,25 (OH)2 vitamin D3, but not with 25 (OH) vitamin D3, nuclear uptake is prevented. Experiments with 3H 25 (OH) vitamin D3, in contrast to

W. E. Stumpf; M. Sar; F. A. Reid; S. Huang; R. Narbaitz; H. F. DeLuca



Correlates of parathyroid hormone concentration in hemodialysis patients  

PubMed Central

Background The implications of chemical hyperparathyroidism on bone and mineral metabolism measures in maintenance hemodialysis (MHD) are not well known. We hypothesized that a higher serum intact parathyroid hormone (iPTH) level is associated with the higher likelihood of hyperphosphatemia, hyperphosphatasemia [high serum alkaline phosphatase (ALP) levels] and hypercalcemia. Methods Over an 8-year period (July 2001–June 2009), we identified 106 760 MHD patients with iPTH and calcium (Ca), phosphorous (P) and ALP data from a large dialysis clinic. Logistic regression models were examined to assess the association between serum iPTH increments and the likelihood of hyperphosphatemia (P ?5.5 mg/dL), hypercalcemia (Ca ?10.2 mg/dL) and hyperphosphatasemia (ALP ?120 U/L). Results Patients were 61 ± 16 years old and included 45% women, 59% diabetics and 33% Blacks. Compared with an iPTH level of 100 to <200 pg/mL, patients with an iPTH level of 600–700, 700 to <800 and ?800 pg/mL had 122% (OR: 2.22, 95% CI: 2.04–2.41), 153% (OR: 2.53, 95% CI: 2.29–2.80) and 243% (OR: 3.43, 95% CI: 3.22–3.66) higher risk of hyperphosphatemia, respectively, and had 109% (OR: 2.09, 95% CI: 1.93–2.26), 130% (OR: 2.30, 95% CI: 2.10–2.52) and 376% (OR: 4.76, 95% CI: 4.50–5.04) higher risk of hyperphosphatasemia, respectively. Compared with an iPTH level of 100 to <200 pg/mL, both the low iPTH (<100 pg/mL, OR: 2.45, 95% CI: 2.27–2.64) and the high iPTH (?800 pg/mL: OR: 2.13, 95% CI: 1.95–2.33) levels were associated with hypercalcemia. Conclusions Higher levels of iPTH are incremental correlates of hyperphosphatemia and hyperphosphatasemia, whereas both very low and high PTH levels are linked to hypercalcemia. If these associations are causal, correction of hyperparathyroidism may have overarching implications on bone and mineral disorders in MHD patients.

Li, Jinnan; Molnar, Miklos Z.; Zaritsky, Joshua J.; Sim, John J.; Streja, Elani; Kovesdy, Csaba P.; Salusky, Isidro; Kalantar-Zadeh, Kamyar



Evidence for Skeletal Resistance to Parathyroid Hormone in Magnesium Deficiency  

PubMed Central

Hypocalcemia during magnesium (Mg) depletion has been well described, but the precise mechanism(s) responsible for its occurrence is not yet fully understood. The hypocalcemia has been ascribed to decreased parathyroid hormone (PTH) secretion as well as skeletal resistance to PTH. Whereas the former is well established, controversy exists as to whether or not Mg depletion results in skeletal resistance to PTH. These studies examine the skeletal response to PTH in normal dogs and dogs fed a Mg-free diet for 4-6 mo. Isolated tibia from normal (serum Mg 1.83±0.1 mg/100 ml) and experimental dogs (serum Mg 1.34±0.15 mg/100 ml) were perfused with Krebs-Henseleit buffer during a constant infusion of 3 ng/ml of synthetic bovine PTH 1-34 (syn b-PTH 1-34). The arteriovenous (A-V) difference for immunoreactive PTH (iPTH) across seven normal bones was 37.5±3%. In contrast, the A-V difference for iPTH was markedly depressed to 10.1±1% across seven bones from Mg-depleted dogs. These findings correlated well with a biological effect (cyclic AMP [cAMP] production) of syn b-PTH 1-34 on bone. In control bones, cAMP production rose from a basal level of 5.8±0.2 to 17.5±0.7 pmol/min after syn b-PTH 1-34 infusion. In experimental bones, basal cAMP production was significantly lower than in controls, 4.5±0.1 pmol/min, and increased to only 7.1±0.4 pmol/min after syn b-PTH 1-34 infusion. Even when PTH concentrations were increased to 20 ng/ml, cAMP production by experimental bones was lower than in control bones perfused with 3 ng/ml. Histological examination of bones from Mg-deficient dogs showed a picture compatible with skeletal inactivity. These studies demonstrate decreased uptake of iPTH and diminished cAMP production by bone, which indicates skeletal resistance to PTH in chronic Mg deficiency. Images

Freitag, Jeffrey J.; Martin, Kevin J.; Conrades, Mary B.; Bellorin-Font, Ezequiel; Teitelbaum, Steven; Klahr, Saulo; Slatopolsky, Eduardo



A Randomized Trial of Cholecalciferol versus Doxercalciferol for Lowering Parathyroid Hormone in Chronic Kidney Disease  

PubMed Central

Background and objectives: The optimal treatment of secondary hyperparathyroidism in chronic kidney disease (CKD) is unknown. Design, setting, participants, & measurements: We conducted a randomized, blinded, 3-month trial in vitamin D-deficient CKD stage 3 and 4 patients with parathyroid hormone (PTH) values above the Kidney Disease Outcomes Quality Initiative target, comparing cholecalciferol (4000 IU/d × 1 month, then 2000 IU/d; n = 22) to doxercalciferol (1 ?g/d; n = 25). Results: There was no difference in baseline demographics or lab tests, except a slightly higher estimated GFR (eGFR) in the doxercalciferol group. There was a significant increase in vitamin D level in the cholecalciferol group (14 ± 6 to 37 ± 10 ng/ml; P < 0.001) but no change in the doxercalciferol group. The PTH decreased by 27% ± 34% in the doxercalciferol group (P = 0.002) and decreased by 10% ± 31% in the cholecalciferol group (P = 0.16), but the difference between treatments was NS (P = 0.11). Similar results were found when absolute PTH change from baseline to end point was analyzed in a repeated-measures ANOVA model. The serum calcium and urine calcium excretions were not different. Additional non-mineral-related end points, albuminuria, and BP were evaluated, and although trends were present, this did not reach significance. Conclusions: This prospective, randomized trial demonstrated a within-group reduction in PTH in the doxercalciferol-treated patients but no significant difference between the doxercalciferol and cholecalciferol patients. Larger, long-term studies are needed to demonstrate efficacy of mineral-related and non-mineral-related end points and safety.

Saifullah, Akber; LaClair, Robert E.; Usman, Sohail A.; Yu, Zhangsheng



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

PubMed Central

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

Karyagar, Savas; Karyagar, Sevda S; Yalc?n, Orhan; Yuney, Enis; Mulaz?moglu, Mehmet; Ozpacac?, Tevfik; Karatepe, Oguzhan; Ozdenkaya, Yasar



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


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

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



Resistance to the Phosphaturic and Calcemic Actions of Parathyroid Hormone during Phosphate Depletion  

PubMed Central

Recent observations indicate that in thyroparathyroidectomized (TPTX) rats fed a low (0.2 g/100 g) phosphorus diet, the tubular phosphaturic response to parathyroid hormone (PTH) remains markedly blunted even when it is assessed at normal or high plasma concentration and filtered load of inorganic phosphate (Pi). Because 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] decreases the tubular capacity to reabsorb Pi when chronically administered to TPTX rats, we have studied whether this vitamin D3 metabolite could specifically increase the phosphaturic response to PTH in phosphate-deprived animals. The results show that in Vitamin D-replete TPTX rats fed a low (0.2 g/100 g) phosphorus diet, 1,25(OH)2D3 (2 × 13 pmol/d i.p. for 7 d) markedly enhanced the acute tubular phosphaturic response to PTH (2.5 IU/h i.v.) without affecting the action of the peptide hormone on Ca reabsorption and cyclic-3?,5?-AMP excretion. The influence of 1,25(OH)2D3 on the phosphaturic response to PTH could not be ascribed to an increased plasma concentration and(or) filtered load of Pi during the administration of the peptide hormone. However, it could be, at least in part, related to the elevation in the basal level of plasma Pi which was observed in the 1,25(OH)2D3-treated animals. The results also indicate that 1,25(OH)2D3 significantly enhanced the calcemic response to PTH, which was blunted in these conditions of phosphate deprivation. Unlike 1,25-(OH)2D3, 25-hydroxyvitamin D3 did not unmask the phosphaturic effect of PTH in phosphate-depleted animals, even when given in doses 100 times larger. Thus, 1,25(OH)2D3 displays a selective and powerful activity in preventing the occurrence of tubular resistance to the phosphaturic action of PTH during Pi depletion. This finding suggests the existence of an important interaction between dietary Pi, 1,25(OH)2D3, and PTH in the homeostasis of phosphate.

Gloor, H. J.; Bonjour, J-P.; Caverzasio, J.; Fleisch, H.



The Vitamin D Receptor (VDR) Start Codon Polymorphism in Primary Hyperparathyroidism and Parathyroid VDR Messenger Ribonucleic Acid Levels  

Microsoft Academic Search

Vitamin D regulates parathyroid cell proliferation and secretion of PTH. Increased prevalence of the polymorphic vitamin D receptor (VDR) alleles b, a, and T has been reported in sporadic primary hyperparathyroidism (PHPT), suggesting that these genetic variants may predispose to the disease. Recently, another polymorphism in the VDR gene was related to bone mineral density, and this VDR-FokI polymorphism causes



Haploinsufficiency of Parathyroid Hormone-Related Peptide (PTHrP) Results in Abnormal Postnatal Bone Development  

Microsoft Academic Search

Although apparently phenotypically normal at birth, mice heterozygous for inactivation of the gene encoding parathyroid hormone-related peptide (PTHrP) develop haplotype insufficiency by 3 months of age. In addition to histologic and morphologic abnormalities similar to those seen in homozygous mutants, heterozygous animals demonstrated alterations in trabecular bone and bone marrow. These included metaphyseal bone spicules which were diminished in volume,

Norio Amizuka; Andrew C. Karaplis; Janet E. Henderson; Hershey Warshawsky; Mark L. Lipman; Yutaka Matsuki; Sadakazu Ejiri; Mikako Tanaka; Naoya Izumi; Hidehiro Ozawa; David Goltzman



Immunocytochemical evidence for endogenous calcitonin and parathyroid hormone in osteoblasts from the calvaria of neonatal mice  

Microsoft Academic Search

Immunoreactivities to endogenous calcitonin, endogenous parathyroid hormone, endogenous estradiol and estradiol receptors were studied in osteoblasts from the calvaria of neonatal mice by immunocytochemistry with the use of ultrathin sections obtained by cryo-ultramicrotomy. Tissues were fixed in glutaraldehyde, postfixed in osmium tetroxide and frozen in liquid nitrogen. Estradiol and estradiol receptors could not be detected in osteoblasts, whereas calcitonin- and

G. Morel; G. Boivin; L. David; P. M. Dubois; P. J. Meunier



Hyperphosphatemia Modestly Retards Parathyroid Hormone Suppression during Calcitriol-Induced Hypercalcemia in Normal and Azotemic Rats  

Microsoft Academic Search

Background\\/Aims: In in vitro studies, a high phosphate concentration has been shown to directly stimulate parathyroid hormone (PTH) secretion in a normal calcium concentration and to reduce PTH suppression in a high calcium concentration. In hemodialysis patients during dialysis-induced hypercalcemia, the effect of hyperphosphatemia on PTH secretion was less than in vitro studies. Our goal was to determine whether hyperphosphatemia

Aquiles Jara; Cecilia Chacón; Arnold J. Felsenfeld



Inhibition of Parathyroid Hormone: A Dose Equivalency Study of Paricalcitol and Doxercalciferol  

Microsoft Academic Search

Introduction: Paricalcitol and doxercalciferol are effective in reducing parathyroid hormone PTH concentrations in patients with secondary hyperparathyroidism. The purpose of this study was to determine the relative dose of doxercalciferol (compared to paricalcitol) required to maintain equivalent PTH concentrations in dialysis patients. Methods: Chronic hemodialysis patients treated with a stable dose of paricalcitol for at least 3 months were randomized

Anna L. Zisman; Walid Ghantous; Pamela Schinleber; Laurie Roberts; Stuart M. Sprague




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


Indoxyl sulfate induces skeletal resistance to parathyroid hormone in cultured osteoblastic cells  

Microsoft Academic Search

Skeletal resistance to parathyroid hormone (PTH) is well known to the phenomenon in chronic renal failure patient, but the detailed mechanism has not been elucidated. In the process of analyzing an animal model of renal failure with low bone turnover, we demonstrated decreased expression of PTH receptor (PTHR) accompanying renal dysfunction in this model. In the present study, we focused

T Nii-Kono; Y Iwasaki; M Uchida; A Fujieda; A Hosokawa; M Motojima; H Yamato; K Kurokawa; M Fukagawa



Postoperative Elevated Serum Levels of Intact Parathyroid Hormone after Surgery for Parathyroid Adenoma: Sign of Bone Remineralization and Decreased Calcium Absorption  

Microsoft Academic Search

.   Increased levels of intact parathyroid hormone (PTH) have been documented after surgery for primary hyperparathyroidism (pHPT)\\u000a despite normocalcemia. The pathogenesis remains to be elucidated. Seventeen consecutive patients operated on for solitary\\u000a parathyroid adenoma were investigated before and at 8 weeks and 1 year after surgery with serum levels of intact PTH, biochemical\\u000a variables known to reflect PTH activity, and

Johan Westerdahl; Stig Valdemarsson; Pia Lindblom; Anders Bergenfelz



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

Microsoft Academic Search

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

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



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

SciTech Connect

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

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



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

PubMed Central

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



Parathyroid hormone determination in ultrasound-guided fine needle aspirates allows the differentiation between thyroid and parathyroid lesions: our experience and review of the literature.  


In many cases, it is difficult or even impossible to distinguish parathyroid lesions from thyroid ones at ultrasound as well as at scintiscan and even at cytology, because they often share common features. The aim of this study was to evaluate the role of Parathyroid Hormone (PTH) determination in the aspirates in the differential diagnosis of parathyroid from thyroid lesions in an area of mild iodine deficiency and high prevalence of thyroid nodules. Forty-six consecutive patients were suspected to have one or more nodule(s) of parathyroid origin because of their position in the posterior aspect of thyroid lobes and/or their shape and echo-pattern at ultrasound examination. In 13 cases, there were also laboratory findings suggestive for primary hyperparathyroidism, with clinical evidence in 6 of these patients. A total of 55 lesions suspected to be of parathyroid origin were selected. After obtaining cytological preparations, the needle used to perform the fine-needle aspirate (FNA) was washed using 1 ml of normal saline. Intact PTH determination in the washout was done whereas the evaluation was performed directly in the aspirated fluid in case of cystic lesions. The values of PTH in the aspirates ranged from 6.7 to 16640 pg/ml. Sixteen patients underwent surgical intervention and the histological examination of the 23 operated lesions previously submitted to FNA-PTH showed 11 parathyroid adenomas, 5 hyperplasic parathyroid lesions and 7 benign thyroid nodules. A strong positive correlation between high levels of PTH in the aspirate and the histological findings of parathyroid lesions was found. A value over 245 pg/ml was constantly associated to the parathyroid lesions. Our results confirmed the high accuracy of FNA-PTH determination in differentiating parathyroid lesions from thyroid nodules and this is of special value in an area of mild iodine deficiency with a high prevalence of thyroid nodules. PMID:24397729

Triggiani, Vincenzo; Resta, Francesco; Giagulli, Vito A; Iovino, Michele; Licchelli, Brunella; De Pergola, Giovanni; Tafaro, Angela; Benigno, Marcello; Sabbà, Carlo; Guastamacchia, Edoardo



About the Parathyroid Glands  


... make and secrete more of their active hormoneparathyroid hormone (PTH). This sets off a chain of events ... a kidney stone should have blood calcium and parathyroid hormone measured. There are even more subtle changes that ...


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

Microsoft Academic Search

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

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



Expression-level dependent activation of recombinant human parathyroid hormone/parathyroid hormone-related peptide receptor: effect of human parathyroid hormone (1-34), (1-31), and (28-48).  


A stable recombinant chinese hamster ovary (CHO) cell model system expressing the human type-1 receptor for parathyroid hormone and parathyroid hormone-related peptide (hPTH-R) was established for the analysis of human PTH (hPTH) variants. The cell lines showed receptor expression in the range from 10(5) to I.9 x 10(6) receptors per cell. The affinity of the receptors for hPTH-(1-34) was independent of the receptor number per cell (Kd approximately = 8 nmol/1). The induction of cAMP by hPTH-(1-34) is maximal in clones expressing >2x10(5) receptors per cell and Ca++ signals were maximal in cell lines expressing >1.4x10(6) receptors per cell. Second messenger specific inhibitors demonstrated that PTH-induced increases in intracellular cAMP and Ca++ are independent and Ca++ ions are derived from intracellular stores. The cAMP-specific receptor activator hPTH-(1-31) showed also an increase in intracellular Ca++. Even in cell lines expressing more than 10(6) receptors per cell the Ca++/PKC specific activator hPTH-(28-48) did not activate hPTH-Rs. Based on these results, synthesis of further derivatives of PTH is required to identify pathway-specific ligands for the type-1 hPTH-R. PMID:10994650

Tonn, O; Kriegbaum, S; Braitmaier, A; Schäfer, W; Esswein, A; Dony, C; Kaluza, K; Honold, K



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



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


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



Association of Serum Intact Parathyroid Hormone with Lower Estimated Glomerular Filtration Rate  

PubMed Central

Background and objectives: The prevalence of mineral metabolism abnormalities is almost universal in stage 5 chronic kidney disease (CKD), but the presence of abnormalities in milder CKD is not well characterized. Design, setting, participants, & measurements: Data on adults ?20 yr of age from the National Health and Nutrition Examination Survey 2003–2004 (N = 3949) were analyzed to determine the association between moderate declines in estimated GFR (eGFR), calculated using the Modfication of Diet in Renal Disease formula, and serum intact parathyroid hormone (iPTH) ? 70 pg/ml. Results: The geometric mean iPTH level was 39.3 pg/ml. The age-standardized prevalence of elevated iPTH was 8.2%, 19.3%, and 38.3% for participants with eGFR ? 60, 45 to 59, and 30 to 44 ml/min/1.73 m2, respectively (P-trend < 0.001). After adjustment for age; race/ethnicity; sex; menopausal status; education; income; cigarette smoking; alcohol consumption; body mass index; hypertension; diabetes mellitus; vitamin D supplement use; total calorie and calcium intake; and serum calcium, phosphorus, and 25-hydroxyvitamin D levels—and compared with their counterparts with an eGFR ? 60 ml/min/1.73 m2—the prevalence ratios of elevated iPTH were 2.30 and 4.69 for participants with an eGFR of 45 to 59 and 30 to 44 ml/min/1.73 m2, respectively (P-trend < 0.001). Serum phosphorus ? 4.2 mg/dl and 25-hydroxyvitamin D < 17.6 ng/ml were more common at lower eGFR levels. No association was present between lower eGFR and serum calcium < 9.4 mg/dl. Conclusions: This study indicates that elevated iPTH levels are common among patients with moderate CKD.

Muntner, Paul; Jones, Tiffany M.; Hyre, Amanda D.; Melamed, Michal L.; Alper, Arnold; Raggi, Paolo; Leonard, Mary B.



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




Role of the fetal parathyroid glands and parathyroid hormone-related protein in the regulation of placental transport of calcium, magnesium and inorganic phosphate.  


The plasma Ca concentration of the fetus is maintained higher than maternal levels by active placental transport. Ca, Mg and PO4 accumulation by the fetus is mainly associated with skeletal growth. The fetal parathyroid glands are essential for maintenance of elevated plasma Ca, which is necessary for the stimulation of fetal osteoblasts and mineralization of cartilage and osteoid. Fetal thyroparathyroidectomy (TxPTx) results in a decreased activity of the placental Ca pump. The presence of a parathyroid hormone-related protein (PTHrP) has been demonstrated in fetal parathyroid glands and placental tissue. Extracts of fetal parathyroid glands and purified PTHrP, as well as recombinant PTHrP (1-84, 1-108 and 1-141), stimulate Ca and Mg but not PO4 transport across the placenta of TxPTx-ized fetuses perfused with autologous blood in the absence of the fetus. Parathyroid hormone (PTH) and the N-terminal region of PTHrP do not stimulate placental Ca and Mg transport. It is concluded that a mid-molecule region of this novel hormone may be required to stimulate placental Ca transfer and contribute to the regulation of fetal Ca homeostasis. PMID:1957034

MacIsaac, R J; Heath, J A; Rodda, C P; Moseley, J M; Care, A D; Martin, T J; Caple, I W



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

Microsoft Academic Search

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




Effects of parathyroid hormone on alkaline phosphatase activity and mineralization of cultured chick embryo tibiae  

Microsoft Academic Search

Summary  The objectives of this study were (a) to determine if decreased bone alkaline phosphatase (AlPase) activity, resulting either\\u000a from exposure to parathyroid hormone (PTH) or from direct inhibition of AlPase with levamisole, was concomitant with net changes\\u000a in bone Ca and P content; and (b) to determine the duration of the effect of PTH on bone AlPase activity after the

M. L. Thomas; W. K. Ramp



Selective stimulation of net calcium efflux from chick embryo tibiae by parathyroid hormone in vitro  

Microsoft Academic Search

Summary The purpose of this study was to measure in an in vitro system the movement of Ca and phosphate (Pi) out of bone when treated with parathyroid hormone (PTH). Tibiae from 13-day chick embryos were incubated for up to 8 h in a defined medium containing 1.8 mM Ca. Medium samples were collected every 2 h and were analyzed

W. K. Ramp; R. W. McNeil



Acute Effects of 2 Hours of Moderate-Intensity Cycling on Serum Parathyroid Hormone and Calcium  

Microsoft Academic Search

Previous studies have found that serum parathyroid hormone (PTH) increases in response to relatively short (<60 minutes),\\u000a intense bouts of exercise, possibly as a result of decreases in serum calcium. Whether longer, less intense exercise also\\u000a stimulates an increase in PTH is not known. The effects of 2 hours of moderate-intensity cycling on serum PTH and calcium\\u000a were investigated in

Daniel W. Barry; Wendy M. Kohrt



Dynamic tests of parathyroid hormone secretion using hemodialysis and calcium infusion cannot be compared  

Microsoft Academic Search

Dynamic tests of parathyroid hormone secretion using hemodialysis and calcium infusion cannot be compared.BackgroundExtracellular Ca++ concentration [Ca++] and parathormone (PTH) are related by a sigmoidal function. The set point of the control system is the [Ca++] that produces a half-maximal inhibition of PTH secretion. Whether or not this set point is abnormal in patients with chronic renal failure (CRF) and

Rosa M. A. Moyses; Renata Cristina Pereira; Luciene Machado Dos Reis; Emil Sabbaga; Vanda Jorgetti



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



Effects of Nigella sativa and human parathyroid hormone on bone mass and strength in diabetic rats  

Microsoft Academic Search

Osteoporosis is a major complication in patients with diabetes mellitus (DM), particularly in those with insulin dependency.\\u000a Recently, many therapeutic effects ofNigella sativa L. (NS) extracts have been exhibited such as anti-inflammatory, antitumor, and antidiabetic with clinical and experimental\\u000a studies. Mechanical strength in the femur and vertebrae increases with human parathyroid hormone (hPTH) treatment. The aim\\u000a of the present study

Mehmet Fatih Altan



The expression of functional human parathyroid hormone in a gene therapy model for osteoporosis  

Microsoft Academic Search

The pro-peptide sequence of human parathyroid hormone (hPTH) is essential for the efficient translocation of the nascent polypeptide and the precise cleavage at residue +1 from the cleavage site. If residue +1 is not a serine, the bioactivity of hPTH decreases dramatically. In order to express the functional hPTH properly in a gene therapy model, we constructed three sets of

Bainan Liu; Jianguo Tang; Jianguo Ji; Jun Gu



Expression and Signaling of Parathyroid Hormone-Related Protein in Cultured Podocytes  

Microsoft Academic Search

Podocyte function appears to be regulated by vasoactive factors. In vivo podocytes express parathyroid hormone-related protein (PTHrP), the N-terminal fragment of which has vasoactive properties. Since the signaling pathway(s) of PTHrP(1–36) are unknown in podocytes, differentiated cells of a conditionally immortalized mouse podocyte cell line were studied. Gene expression of PTHrP and the PTH\\/PTHrP receptor was investigated by RT-PCR; protein

Nicole Endlich; Rainer Nobiling; Wilhelm Kriz; Karlhans Endlich



Parathyroid Hormone-Related Protein Localization in Breast Cancers Predict Improved Prognosis  

Microsoft Academic Search

In a prospective study of 526 consecutive patients with operable breast cancer, the significance of positive parathyroid hormone-related protein (PTHrP) staining by immunohistology has been evaluated for a median of 10-year follow-up. Improved survival was observed for the 79% of tumors which stained positively for PTHrP (estimated univariate hazard ratio, 0.43; 95% confidence interval (95% CI), 0.30-0.62; P < 0.001).

Michael A. Henderson; Janine A. Danks; John L. Slavin; Graham B. Byrnes; Peter F. M. Choong; John B. Spillane; John L. Hopper; T. John Martin


Intact serum parathyroid hormone levels increase during running exercise in well-trained men  

Microsoft Academic Search

The purpose of this study was to examine the influence of exercise on the serum concentrations of intact parathyroid hormone (PTH). Serum PTH and plasma lactate were measured in 15 well-trained men, 9 long-distance runners and 6 fire-fighters, during two running exercises. Test one consisted of 40-minute treadmill running with a stepwise increased load and test two consisted of 50-minute

H. Salvesen; A. G. Johansson; P. Foxdal; L. Wide; K. Piehl-Aulin; S. Ljunghall



Effects of prednisone and deflazacort on mineral metabolism and parathyroid hormone activity in humans  

Microsoft Academic Search

Summary  The effects of two different glucocorticoids, prednisone and deflazacort, (an oxazoline derivative of prednisolone) on bone\\u000a metabolism were analyzed in 10 patients with disorders that required glucocorticoid therapy. Significant elevations in blood\\u000a immunoreactive parathyroid hormone, alkaline phosphatase and urinary calcium, phosphate, hydroxyproline and nephrogenous cyclic\\u000a AMP were observed during prednisone therapy in addition to an increase in the exchangeable calcium

C. Gennari; B. Imbimbo; M. Montagnani; M. Bernini; P. Nardi; L. V. Avioli



Indomethacin does not inhibit the anabolic effect of parathyroid hormone on the long bones of rats  

Microsoft Academic Search

Summary  Chronic administration of parathyroid hormone, hPTH 1-34, increased bone mass in normocalcemic, young rats [6]. Since PTH\\u000a can stimulate prostaglandin E2 (PGE2) production in bonein vitro, and since PGE2 can stimulate bone formation, the anabolic effect of PTH could be mediated by PGE2. To test this hypothesis, experiments were done to determine if indomethacin, which blocks endogeneous PG production, would

I. Gera; J. M. Hock; M. Gunness-Hey; J. Fonseca; L. G. Raisz



Functional asymmetry in phosphate transport and its regulation in opossum kidney cells: parathyroid hormone inhibition  

Microsoft Academic Search

The sidedness (apical vs basolateral) of the inhibitory of phosphate (Pi) transport by parathyroid hormone (PTH) was investigated in opossum kidney (OK)-cell monolayers grown on permeant support. PTH was found to regulate the activity of only the apical Na\\/Pi cotransporter, having no effect on the basolateral transport systems. Transport inhibition was approximately 100-fold more sensitive to apical PTH application (Kd:

Stephan J. Reshkin; Judith Forgo; Heini Murer



Effects of parathyroid hormone on odontogenesis of the mouse embryonic molar tooth In vitro  

Microsoft Academic Search

Summary  Mandibular first molars of 17-day-old mouse embryos were culturedin vitro to examine the histological effects of various concentrations of parathyroid hormone (PTH) on odontogenesis of the molars.\\u000a PTH did not affect the cytodifferentiation of mesenchymal cells into preodontoblasts but inhibited that of preodontoblasts\\u000a into odontoblasts. Consequently, the odontoblasts failed to undergo dentinogenesis. On the other hand, inner enamel epithelium\\u000a achieved

Y. Sakakura



Prostaglandin E2 and parathyroid hormone: Comparisons of their actions on the rabbit proximal tubule  

Microsoft Academic Search

Prostaglandin E2 and parathyroid hormone: Comparisons of their actions on the rabbit proximal tubule. Recent studies demonstrated that prostaglandin E2 (PGE2) participates in the regulation of glomerular and distal tubular function. A functional role for PGE2 on the proximal tubule has only recently been explored. Thus, we reported that PGE2 antagonizes the phosphaturic effect of PTH in the dog, which

Jesus H Dominguez; Thomas O Pitts; Thomas Brown; Diane B Puschett; Frederick Schuler; Tai C Chen; Jules B Puschett



Carboxyl-terminal fragments of human parathyroid hormone in parathyroid tumors: unique new source of immunogens for the production of antisera potentially useful in the radioimmunoassay of parathyroid hormone in human serum.  


We have found large quantities of immunoreactive carboxyl-terminal fragments of human parathyroid hormone )hPTH) in a previously discarded fraction [the 7.5% trichloroacetic acid (TCA)supernate] generated during extraction of intact hPTH from hyperfunctioning parathyroid tissue by the urea-TCA procedure. It is well established that serum RIAs directed toward the carboxyl-terminal region of hPTH are superior to those directed toward the amino-terminal region in the differential diagnosis of patients with suspected chronic parathyroid dysfunction. However, antisera that react with the carboxyl-terminal region of hPTH are not yet available for general use for these assays because of a lack of suitable hPTH immunogens. We immunized seven guinea pigs and two goats with the desalted 7.5% TCA supernate (containing about 2% carboxyl-terminal hPTH fragments); three of the guinea pigs and one goat produced high affinity antisera with predominant specificity for the carboxyl-terminal region of PTH. One of the guinea pig antisera had affinity for hPTH equal to that of our laboratory's best antiserum (GP1M) used in diagnostic RIAs for serum PTH. The use of this byproduct fraction as an immunogen should permit a large scale immunization program in large animals to provide standardized, species-and sequence-specific antisera potentially useful in RIAs for diagnosis of parathyroid disease. PMID:755044

Di Bella, F P; Gilkinson, J B; Flueck, J; Arnaud, C D



Developmental Cues for Bone Formation from Parathyroid Hormone and Parathyroid Hormone-Related Protein in an Ex Vivo Organotypic Culture System of Embryonic Chick Femora  

PubMed Central

Enhancement and application of our understanding of skeletal developmental biology is critical to developing tissue engineering approaches to bone repair. We propose that use of the developing embryonic femur as a model to further understand skeletogenesis, and the effects of key differentiation agents, will aid our understanding of the developing bone niche and inform bone reparation. We have used a three-dimensional organotypic culture system of embryonic chick femora to investigate the effects of two key skeletal differentiation agents, parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP), on bone and cartilage development, using a combination of microcomputed tomography and histological analysis to assess tissue formation and structure, and cellular behavior. Stimulation of embryonic day 11 (E11) organotypic femur cultures with PTH and PTHrP initiated osteogenesis. Bone formation was enhanced, with increased collagen I and STRO-1 expression, and cartilage was reduced, with decreased chondrocyte proliferation, collagen II expression, and glycosaminoglycan levels. This study demonstrates the successful use of organotypic chick femur cultures as a model for bone development, evidenced by the ability of exogenous bioactive molecules to differentially modulate bone and cartilage formation. The organotypic model outlined provides a tool for analyzing key temporal stages of bone and cartilage development, providing a paradigm for translation of bone development to improve scaffolds and skeletal stem cell treatments for skeletal regenerative medicine.

Kanczler, Janos M.; Roberts, Carol A.; Oreffo, Richard O.C.



Developmental cues for bone formation from parathyroid hormone and parathyroid hormone-related protein in an ex vivo organotypic culture system of embryonic chick femora.  


Enhancement and application of our understanding of skeletal developmental biology is critical to developing tissue engineering approaches to bone repair. We propose that use of the developing embryonic femur as a model to further understand skeletogenesis, and the effects of key differentiation agents, will aid our understanding of the developing bone niche and inform bone reparation. We have used a three-dimensional organotypic culture system of embryonic chick femora to investigate the effects of two key skeletal differentiation agents, parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP), on bone and cartilage development, using a combination of microcomputed tomography and histological analysis to assess tissue formation and structure, and cellular behavior. Stimulation of embryonic day 11 (E11) organotypic femur cultures with PTH and PTHrP initiated osteogenesis. Bone formation was enhanced, with increased collagen I and STRO-1 expression, and cartilage was reduced, with decreased chondrocyte proliferation, collagen II expression, and glycosaminoglycan levels. This study demonstrates the successful use of organotypic chick femur cultures as a model for bone development, evidenced by the ability of exogenous bioactive molecules to differentially modulate bone and cartilage formation. The organotypic model outlined provides a tool for analyzing key temporal stages of bone and cartilage development, providing a paradigm for translation of bone development to improve scaffolds and skeletal stem cell treatments for skeletal regenerative medicine. PMID:22690868

Smith, Emma L; Kanczler, Janos M; Roberts, Carol A; Oreffo, Richard O C



Circulating intact parathyroid hormone is suppressed at 25-hydroxyvitamin D concentrations >25 nmol/L in children.  


Abstract Vitamin D status is best reflected by circulating concentrations of 25-hydroxyvitamin D2 and D3 (25-OH-D). An adequate blood concentration of total 25-OH-D is commonly defined as that which maintains parathyroid hormone (PTH) within the normal range. Consensus from studies of adults with renal impairment indicates that 75 nmol/L of 25-OH-D maintains suppression of PTH. No similar consensus exists in children. We studied the correlation of PTH and 25-OH-D in 271 patients aged 2 months to 21 years (mean 11 years) in a tertiary care pediatric setting. Patients with renal impairment were excluded by elevated creatinine concentration and chart review. PTH did not significantly correlate with 25-OH-D concentrations >25 nmol/L. PTH was significantly elevated in specimens with <25 nmol/L of 25-OH-D (p=10-17). Using PTH suppression as indicator, these data suggest that 25-OH-D concentrations >25 nmol/L in children indicate vitamin D sufficiency. PMID:24572984

Crews, Bridgit O; Moore, Jennifer; Dietzen, Dennis J



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.



Early changes in parathyroid hormone concentrations in HIV-infected patients initiating antiretroviral therapy with tenofovir.  


Initiation of combined antiretroviral therapy (cART) is associated with bone loss, which may be more intense with regimens including tenofovir. The underlying mechanisms are not well understood. Cross-sectional data have linked tenofovir with higher parathyroid hormone (PTH) concentrations in patients with vitamin D deficiency. We performed a longitudinal study with a 48-week follow-up to evaluate sequential changes in PTH and 25-hydroxyvitamin D [25(OH)D] levels in patients starting cART with either tenofovir/emtricitabine or abacavir/lamivudine. Fifty-seven patients were included, 31 initiating tenofovir/emtricitabine and 26 initiating abacavir/lamivudine. Median PTH levels turned out to be significantly higher among tenofovir/emtricitabine users at week 4 (p=0.01), week 24 (p=0.008), and week 36 (p=0.02), and were above the upper limits of normal values (ULN) at weeks 24, 36, and 48 only in patients receiving tenofovir/emtricitabine. 25(OH)D, serum and urine calcium and phosphate, and renal-tubular maximum reabsorption of phosphate to the glomerular filtration rate (TmP/GFR) levels did not differ between the two treatment arms over the study period. Among tenofovir/emtricitabine users, median (interquartile range) PTH concentrations were significantly higher in patients with suboptimal 25(OH)D levels (<30 ?g/liter) at week 24 [63 (57.8-82.4) ng/liter vs. 54.3 (34.4-63.067.5) ng/liter, p=0.05] and week 48 [67.5 (59.6-86.0) ng/liter vs. 41.9 (37.3-68.8) ng/liter, p=0.03]. A multivariable logistic regression model showed that tenofovir/emtricitabine use was an independent predictor of high PTH levels (?53 ng/liter). Starting cART with tenofovir regimens is associated with an elevation in PTH plasma concentrations soon after introducing the drug. Suboptimal baseline 25(OH)D levels increase the risk of developing secondary hyperparathyroidism among tenofovir users. PMID:21639815

Masiá, Mar; Padilla, Sergio; Robledano, Catalina; López, Natividad; Ramos, José Manuel; Gutiérrez, Felix



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)




PubMed Central

Background and purpose The parathyroid hormone 2 receptor (PTH2R) is a G protein coupled receptor. Pharmacological and anatomical evidence suggests that the recently identified tuberoinfundibular peptide of 39 residues is, and parathyroid hormone and parathyroid hormone-related peptide are not, its endogenous ligand. Initial functional studies suggest that the PTH2R is involved in the regulation of viscerosensory information processing. As a first step towards clinical applications, herein we describe the presence of the PTH2R in the human brain-stem. Material and methods Total RNA was isolated from postmortem human cortical and brainstem samples for RT-PCR. Good quality RNA, as assessed on formaldehyde gel, was reverse transcribed. The combined cDNA products were used as template in PCR reactions with primer pairs specific for the human PTH2R. In addition, PTH2R immunolabelling was performed on free floating sections of the human medulla oblongata using fluorescent amplification immunochemistry. Results Specific bands in the RT-PCR experiments and sequencing of PCR products demonstrated the expression of PTH2R mRNA in the human brainstem. A high density of PTH2R-immunoreactive fibers was found in brain regions of the medulla oblongata including the nucleus of the solitary tract, the spinal trigeminal nucleus, and the dorsal reticular nucleus of the medulla. Conclusion Independent demonstration of the presence of PTH2R mRNA and immunoreactivity supports the specific expression of the PTH2R in the human brainstem. The distribution of PTH2R-immunoreactive fibers in viscerosensory brain regions is similar to that reported in mouse and rat suggesting a similar role of the PTH2R in human as in rodents. This finding will have important implications when experimental data obtained on the function of the TIP39-PTH2R neuromodulator system in rodents are to be utilized in human.

Bago, Attila G.; Palkovits, Miklos; Usdin, Ted B.; Seress, Laszlo; Dobolyi, Arpad



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

SciTech Connect

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

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



Role of vitamin D and calcium nutrition in disease expression and parathyroid tumor growth in primary hyperparathyroidism: a global perspective.  


Since the classic description by Fuller Albright in the 1940s, primary hyperparathyroidism has evolved from a disease with classic signs and symptoms to a disease in search of symptoms! Since that time, two major events have occurred. First, in the United States, United Kingdom, and in most European countries, there has been a steady rise in the apparent incidence of the disease. Second, there has been a dramatic shift in the pattern of presentation. A majority of patients with primary hyperparathyroidism in countries with multichannel screening panels are asymptomatic. Skeletal and renal complications are uncommon, and osteitis fibrosa is rare. In contrast, the clinical presentation of primary hyperparathyroidism has changed very little in other regions such as the East, the Middle East, and some parts of the southern hemisphere over the same period of observation. Accordingly, we assessed the influence of vitamin D and calcium nutrition on the disease expression and parathyroid tumor growth in patients with primary hyperparathyroidism from different parts of the world. Between 1945 and 1950, both the prevalence of osteitis fibrosa and parathyroid tumor weight declined dramatically in the United States, coinciding with fortification of milk with vitamin D. In contrast, osteitis fibrosa and parathyroid tumor weight changed very little in parts of the world where vitamin D depletion is endemic. Furthermore, for a comparable degree of vitamin D depletion, Asian Indians have significantly larger tumors compared with Americans (3.95 +/- 2.23 vs. 0.66 +/- 2.84 g; p < 0.001). Within the United States, blacks have larger tumors compared with whites (0.78 +/- 2.87 vs. 0.58 +/- 2.78 g; p < 0.01). However, the slopes of regression between serum 25-hydroxyvitamin D, the best index of vitamin D nutrition, and parathyroid tumor weight, the best available index of parathyroid growth, were not significantly different between Asian Indians, whites, and blacks. We conclude that vitamin D and calcium nutrition of the population affect both the clinical expression and parathyroid tumor growth in patients with primary hyperparathyroidism. It will be of interest to see if the pattern of presentation of primary hyperparathyroidism changes when better nutritional policies are implemented in developing countries. PMID:12412781

Rao, D Sudhaker; Agarwal, Gaurav; Talpos, Gary B; Phillips, Evelyn R; Bandeira, Franciso; Mishra, Saroj K; Mithal, Ambrish



Effects of 25-hydroxyvitamin D level and its change on parathyroid hormone in premenopausal Chinese women  

Microsoft Academic Search

Summary  Optimal levels of 25-hydroxyvitamin D [25(OH)D] were investigated in premenopausal Chinese women. Parathyroid hormone (PTH)\\u000a change at 3 months was associated with change in 25(OH)D but not with baseline levels, and PTH fell even when starting levels\\u000a of 25(OH)D were >40 nmol\\/L, consistent with optimal values for 25(OH)D of ?40 nmol\\/l.\\u000a \\u000a \\u000a \\u000a \\u000a Introduction  The upper level of 25-hydroxyvitamin D [25(OH)D] which constitutes a long-term bone

C. J. Bacon; J. Woo; E. M. C. Lau; C. W. K. Lam; G. D. Gamble; I. R. Reid



Intraoperative Parathyroid Hormone Monitoring in Patients with Recognized Multiglandular Primary Hyperparathyroidism  

Microsoft Academic Search

Background  Intraoperative parathyroid hormone (IOPTH) monitoring reliably predicts cure of primary hyperparathyroidism (PHPT) due to\\u000a single-gland disease. However, its utility in PHPT caused by multiple-gland disease (MGD) is still debated, for both detection\\u000a and prediction of adequate resection. Our hypothesis is that once MGD is encountered during an operation, more stringent criteria\\u000a for determining adequate resection can improve cure rates.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  This

David T. HughesBarbra; Barbra S. Miller; Gerard M. Doherty; Paul G. Gauger



Glucocorticoid Attenuates the Anabolic Effects of Parathyroid Hormone on Fracture Repair  

Microsoft Academic Search

Long-term use of glucocorticoid (GC) not only reduces bone mass and strength, which leads to a greater risk of fracture, but\\u000a also hinders fracture repair. In this study, we produced open fractures in GC-treated mice and investigated the effects of\\u000a human parathyroid hormone 1–34 (hPTH) on fracture repair. Swiss-Webster mice were randomly divided into five groups. Three\\u000a groups of GC-treated

Anthony R. Doyon; Ian K. Ferries; Jiliang Li



Intraoperative parathyroid hormone level in parathyroidectomy: which patients benefit from it?  

PubMed Central

Background Intraoperative parathyroid hormone level (IOPTH) is withdrawn during parathyroidectomy to confirm the success of the procedure. Recently, the importance of IOPTH has been put to question. The purpose of this study is to determine whether IOPTH is necessary for all patients undergoing parathyroidectomy in the presence of frozen section. Materials and methods A cohort study of parathyroidectomies was performed in three university affiliated hospitals during 2007-2012. The patients were divided into two groups. Group 1: Patients with two preoperative concordant imaging localizing a hyperactive gland. Group 2: Patients without two concordant imaging. A comparison of benefit of IOPTH was carried out. Frozen section results were also analyzed to determine sensitivity and predictability of a parathyroid adenoma. Results The study considered 221 patients having parathyroidectomies for primary hyperparathyroidism (PHPT). Of them, 10 were excluded due to incomplete data. Among the remaining, 186 had 2 concordant imaging preoperatively localizing an adenoma. 93.5% of whom were found intraoperatively in that location. IOPTH was not found to be of importance in 98.92% of the preoperative localized adenomas in the presence of frozen section. IOPTH added an estimate of 30.9 minutes on average to the surgery time. Conclusion This study demonstrates that the added operating time associated with IOPTH may not be justified for patients undergoing parathyroidectomy who have 2 concordant imaging preoperatively in the presence of frozen section. This study suggests a simple algorithm, The McGill Parathyroid Protocol (MPP), to help in approaching PHPT patients undergoing parathyroidectomy.



Relationship between serum magnesium and parathyroid hormone levels in hemodialysis patients  

Microsoft Academic Search

Acute magnesium (Mg) infusion decreases patathyroid hormone (PTH) secretion. However, the effect of chronic hypermagnesemia on PTH levels in dialysis patients is not well established. We studied 110 hemodialysis patients (mean age, 55 ± 14 years; time on dialysis, 35 ± 28 months) not receiving vitamin D and undergoing dialysis with an Mg dialysate concentration of 1.2 mg\\/dL. The primary

Juan F. Navarro; Carmen Mora; Alejandro Jiménez; Armando Torres; Manuel Macía; Javier García



Extremely high parathyroid hormone concentrations associated with pityriasis rubra pilaris and monoclonal gammopathy of unknown significance: a clinical dilemma.  


We present a case with extremely high parathyroid hormone (PTH) concentrations in the order of hundred thousands accompanied by dermatological and hematological diseases. After several diagnostic interventions, no malignancy could be demonstrated except monoclonal gammopathy of unknown significance. The dermatological findings were taken to be manifestations of the hematological disease. Since the first serum intact PTH concentration of the patient was found to be higher than 2500 pg/ml, dilution study was performed and found to be 215,977 pg/ml. The high concentration of serum PTH was taken to be falsely high due to assay interference. This concentration was checked from three different paths; a test for linear dilution was performed, the test was repeated with another method and the sample was treated to remove or inhibit interfering substances. The results were compatible with endogenous antibody interference, presumed to be a result of monoclonal gammopathy. The extremely high PTH concentrations were not only due to assay interference, but also secondary hyperparathyroidism, which was evident by the decrease in PTH concentrations with calcium and vitamin D treatments. PMID:22906636

Tanriover, Mine Durusu; Portakal, Oytun; Hapa, Asli; Tekinel, Yasemin; Dagdelen, Selcuk; Buyukasik, Yahya; Arici, Mustafa



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


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

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



Dual role of parathyroid hormone in endothelial progenitor cells and marrow stromal mesenchymal stem cells.  


Hematopoietic stem cells derive regulatory information also from parathyroid hormone (PTH). To explore the possibility that PTH may have a role in regulation of other stem cells residing in bone marrow, such as mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) we assessed the effect of this hormone on the in vitro behavior of MSCs and EPCs. We evidenced that MSCs were much more responsive to PTH than EPCs. PTH increased the proliferation rate of MSCs with a diminution of senescence and apoptosis. Taken together, our results may suggest a protective effect of PTH on MSCs that reduces stress phenomena and preserve genome integrity. At the opposite, PTH did not modify the fate of EPCs in culture. PMID:19918796

Di Bernardo, Giovanni; Galderisi, Umberto; Fiorito, Carmela; Squillaro, Tiziana; Cito, Letizia; Cipollaro, Marilena; Giordano, Antonio; Napoli, Claudio



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

SciTech Connect

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

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



Relationship between serum magnesium, parathyroid hormone, and vascular calcification in patients on dialysis: a literature review.  


Secondary hyperparathyroidism is present in most patients with end-stage renal disease and has been linked to uremic bone disease, vascular calcification, and mortality. Current literature suggests an association between hypomagnesemia and cardiovascular disease in the general population. We reviewed all published studies on the relationship between serum magnesium and parathyroid hormone and the relationship between serum Mg and vascular calcification in dialysis patients. Of these, 10 of 12 studies of patients on hemodialysis and 4 of 5 studies of patients on peritoneal dialysis showed a significantinverse relationship between serum Mg and serum intact parathyroid hormone. Hyperparathyroidism develops in peritoneal dialysis patients dialyzed with a solution containing normal calcium (1.25 mmol/L) and low Mg (0.25 mmol/L), even though serum calcium is maintained at a normal level. Four of the hemodialysis studies and one of the peritoneal dialysis studies indicated that there is an inverse relationship between serum Mg and vascular calcification in these patients. Potential benefits have been attributed to magnesium carbonate as a phosphate binder and it may possibly be an effective, less toxic, less expensive phosphate binder. We believe that the role of Mg in secondary hyperparathyroidism and vascular calcification merits further investigation. PMID:16722031

Wei, Mingxin; Esbaei, Khaled; Bargman, Joanne; Oreopoulos, Dimitrios G



Circadian rhythms for calcium, inorganic phosphorus, and parathyroid hormone in primary hyperparathyroidism: functional and practical considerations.  


We obtained serial serum and urine samples from 14 patients with primary hyperparathyroidism both before and 3 to 9 months after excision of their parathyroid adenomas to (1) determine whether the circadian rhythms for calcium, phosphorus, and parathyroid hormone (PTH) previously described in normal human beings are disturbed in this disorder; (2) gauge the effect of surgical treatment on the patterns observed before intervention; and (3) ascertain whether time(s) of blood sampling can be defined for optimal biochemical detection of the disease. Significant rhythms for serum phosphorus, ionized calcium, PTH, urine phosphorus, and urine calcium were observed in many but not all patients before and after surgery. Nonetheless, collective analysis revealed the following: (1) diurnal patterns for serum ionized calcium, phosphorus, urine calcium, and urine phosphorus in patients with primary hyperparathyroidism both before and after surgery, whereas a rhythm for serum PTH was uniquely observed after surgical treatment; and (2) no significant correlation between preoperative serum ionized calcium and PTH but restoration of the expected reciprocal relationship between these variables after surgery. Although variability in individual expression of the rhythm for PTH precludes precise definition of a sampling "window" when hormone levels are likely to be highest, collection of data at points throughout the day helped establish the diagnosis of primary hyperparathyroidism in several patients with borderline serum biochemistries. PMID:2588106

Lobaugh, B; Neelon, F A; Oyama, H; Buckley, N; Smith, S; Christy, M; Leight, G S



Calcitriol and doxercalciferol are equivalent in controlling bone turnover, suppressing parathyroid hormone, and increasing fibroblast growth factor-23 in secondary hyperparathyroidism.  


We compared the effects of calcitriol and doxercalciferol, in combination with either calcium carbonate or sevelamer, on bone, mineral, and fibroblast growth factor-23 (FGF-23) metabolism in patients with secondary hyperparathyroidism. A total of 60 pediatric patients treated with peritoneal dialysis were randomized to 8 months of therapy with either oral calcitriol or doxercalciferol, combined with either calcium carbonate or sevelamer. Bone formation rates decreased during therapy and final values were within the normal range in 72% of patients. A greater improvement in eroded surface was found in patients treated with doxercalciferol than in those given calcitriol. On initial bone biopsy, a mineralization defect was identified in the majority of patients which did not normalize with therapy. Serum phosphate concentrations were controlled equally well by both binders, but serum calcium levels increased during treatment with calcium carbonate, and serum parathyroid hormone levels were decreased by 35% in all groups. Baseline plasma FGF-23 values were significantly elevated and rose over fourfold with calcitriol and doxercalciferol, irrespective of phosphate binder. Thus, doxercalciferol is as effective as calcitriol in controlling serum parathyroid hormone levels and suppressing the bone formation rate. Sevelamer allows the use of higher doses of vitamin D. Implications of these changes on bone and cardiovascular biology remain to be established. PMID:20861820

Wesseling-Perry, Katherine; Pereira, Renata C; Sahney, Shobha; Gales, Barbara; Wang, He-Jing; Elashoff, Robert; Jüppner, Harald; Salusky, Isidro B



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

PubMed Central

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

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



Effects of parathyroid hormone on blood flow in different regional circulations.  


Parathyroid hormone and, in particular, its 1-34 aminoterminal fragment, PTH-(1-34), are potent vasodilators of the coronary circulation. In addition the hormone exerts a powerful hypotensive effect in a variety of animals, suggesting that the polypeptide hormone is vasoactive in peripheral regional circulations as well. The purpose of this study was to determine the regional circulations that were responsive and the relative sensitivity of each to the vasoactive properties of the hormone fragment. An anesthetized instrumented open-chest and/or open-abdomen dog model was used. Blood flow was continuously monitored in left circumflex, left pulmonary, right renal, celiac, and superior mesenteric arteries. Doses of synthetic human PTH-(1-34) ranging from 0.00024 to 0.24 nmol/kg were administered by bolus intra-arterial injections. Although PTH-(1-34) produced a dose-related vasodilation in each of the above regional vascular beds, marked differences in sensitivity were observed. The peptide elicited large increases in coronary (178%) and celiac (162%) blood flow. Maximal renal and pulmonary responses were relatively small (increases of 30 and 23%, respectively). Compared with control values, blood flow in the superior mesenteric circulation increased only at the highest dose tested. Thus sensitivity to the vascular effects of the hormone fragment differs markedly between the regional vascular beds of the dog. PMID:3661758

Crass, M F; Jayaseelan, C L; Darter, T C



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



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



Effect of treatment for 6 months with human parathyroid hormone (1-34) peptide in ovariectomized cynomolgus monkeys ( Macaca fascicularis)  

Microsoft Academic Search

A potential negative side effect of intermittent parathyroid hormone (PTH) therapy to treat osteoporosis is the loss of cortical bone concomitant with increased cancellous bone mass. We addressed this issue by studying the effects of PTH on whole-body, axial, and appendicular bone mass in an animal model with haversian cortical bone remodeling. Ovariectomized, young adult female cynomolgus monkeys were assigned

C. P Jerome; C. S Johnson; H. T Vafai; K. C Kaplan; J Bailey; B Capwell; F Fraser; L Hansen; H Ramsay; M Shadoan; C. J Lees; J. S Thomsen; L Mosekilde



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

Microsoft Academic Search

Small doses of parathyroid hormone and calcitonin were injected into thyroparathyroidectomized newborn rats to investigate the histological and chemical changes in bone surfaces and in mitochondrial granules of bone lining cells. Nondecalcified tissue specimens were observed under transmission electron microscope, electron probe X-ray microanalyzer, and microdiffraction after freeze substitution preparation of tibia shafts. Amorphous calcium phosphate, which appears as clusters




Evidence that protease inhibitors reduce the degradation of parathyroid hormone and calcitonin injected subcutaneously.  

PubMed Central

1 Agents known to delay absorption from a subcutaneous site were tested in chicks for their ability to prolong the hypercalcaemic response to parathyroid hormone (PTH). 2 Polyvinylpyrrolidone was found to enhance the response but gelatine greatly reduced the 2 h hypercalcaemia. 3 The reduction by gelatine was reversed when the protease inhibitor aprotinin was added to the injection vehicle, and hypercalcaemia then persisted for more than 8 h. 4 Of other protease inhibitors studied, epsilon-aminocaproic acid was also found to enhance the hypercalcaemic response to subcutaneous PTH and its fragments but, unlike aprotinin, it was ineffective in the presence of gelatine. 5 By radioimmunoassay and bioassay respectively, it was confirmed that aprotinin raised circulating levels of PTH and also of another peptide hormone, calcitonin, injected subcutaneously. 6 Addition of calcium to the solutions injected subcutaneously abolished the hypercalcaemic response to PTH while injection of calcium and PTH simultaneously but at separate sites left the response unaltered. 7 The two protease inhibitors, epsilon-aminocaproic acid and aprotinin, each restored the response to subcutaneous PTH despite the presence of calcium at the injection site. 8 It was concluded that protease inhibitors injected subcutaneously with PTH and calcitonin in the chick reduced the rate of degradation of these hormones and that the proteases responsible for hormone degradation at the subcutaneous injection site may be released or activated by calcium ions.

Parsons, J. A.; Rafferty, B.; Stevenson, R. W.; Zanelli, J. M.



Evidence for a novel parathyroid hormone-related protein in fetal lamb parathyroid glands and sheep placenta: comparisons with a similar protein implicated in humoral hypercalcaemia of malignancy.  


Parathyroid hormone (PTH)-like bioactivity, assayed as adenylate cyclase response in UMR 106-01 osteogenic sarcoma cells, was present in extracts of sheep fetal and maternal parathyroid glands and placenta. Preincubation of extracts with PTH(1-34) antiserum inhibited approximately 40% of the bioactivity in fetal parathyroid extracts, 50% in maternal parathyroid extracts, but only 10% of the bioactivity in the placental extract. Partial purification of placental extracts by chromatography yielded fractions containing PTH-like bioactivity which were similar in behaviour to that of PTH-related protein (PTHrP) from a human lung cancer cell line (BEN). An antiserum against synthetic PTHrP(1-16) partially inhibited the bioactivity of the placental extract and synthetic PTHrP(1-34), but had no effect on the bioactivity of bovine PTH(1-34) or bovine PTH(1-84). The placental PTH-like bioactivity was higher in mid- than in late gestation. Fetal parathyroid glands contained the highest PTH-like bioactivity. Thyroparathyroidectomy of one fetal twin lamb in each of 16 ewes between 110 and 125 days of gestation resulted in decreases of the plasma calcium concentration and reversal of the placental calcium gradient that existed between the ewe and the intact fetus. Perfusion of the placenta of each twin in anaesthetized ewes was carried out sequentially with autologous fetal blood in the absence of the exsanguinated fetus. The plasma calcium concentration in the blood perfusing the placenta of each twin increased, but reached a plateau at a lower concentration in the perfusing blood of thyroparathyroidectomized fetuses than in that of the intact fetuses. Addition of extracts of fetal parathyroid glands or of partially purified PTHrP resulted in further increases in plasma calcium in the autologous blood perfusing the placentae of thyroparathyroidectomized fetuses, but addition of bovine PTH(1-84) or rat PTH(1-34) had no effect. The presence of this PTH-like protein in the fetal parathyroid gland and placenta may contribute to the relative hypercalcaemia of the fetal lamb. This protein, which is similar to PTHrP associated with humoral hypercalcaemia of malignancy, stimulates the placental calcium pump responsible for maintaining a relative fetal hypercalcaemia during gestation. PMID:3379358

Rodda, C P; Kubota, M; Heath, J A; Ebeling, P R; Moseley, J M; Care, A D; Caple, I W; Martin, T J



Central venous sampling for intraoperative parathyroid hormone monitoring: are peripheral guidelines applicable?  


Intraoperative parathyroid hormone (PTH) monitoring has become an integral adjunct to minimally invasive parathyroidectomy. Guidelines for predicting therapeutic excision of all hyperactive parathyroid tissue have been routinely based on peripheral blood samples drawn at various time intervals. Whether these same guidelines can be used to predict success based on central blood draws has not been established. The authors wanted to evaluate whether peripheral criteria were applicable when PTH levels were drawn from a central location. Simultaneous peripheral venous (PV) and central venous (CV) PTH samples were drawn from 64 patients undergoing cervical exploration for primary hyperparathyroidism. Median preexcision PTH was significantly higher centrally at 165 pg/mL (interquartile range [IQR], 101-391 pg/mL) versus peripherally 102 pg/mL (interquartile range, 73-156 pg/mL, P < 0.0001). Postexcision PTH was slightly greater in CV (38 pg/mL; IQR, 24-62) than in PV (29 pg/mL; IQR, 22-51; P < 0.0001). The decrease in intraoperative PTH was compared after excision of an initial gland. Fifty-four of the 64 patients had all hyperfunctioning parathyroid tissue removed after initial gland resection. Pre- to postexcision ratios for CV and PV were compared using receiver operating characteristic curve methods, and summarized by area under the curve (AUC). PV (AUC = 0.85) appears to be a slightly more sensitive discriminator than CV (AUC = 0.83), although the difference is not statistically significant (P = 0.5). Despite higher absolute values for CV, both peripheral and central sample sites accurately predict outcomes based on established guidelines for intraoperative PTH monitoring. PMID:17674948

Broome, James T; Schrager, Jason J; Bilheimer, Dean; Chambers, Eugene P; Jacobs, J Kenneth; Phay, John



Prevention of Enhanced Parathyroid Hormone Secretion, Synthesis and Hyperplasia by Mild Dietary Phosphorus Restriction in Early Chronic Renal Failure in Rats: Possible Direct Role of Phosphorus  

Microsoft Academic Search

In order to evaluate the effect of dietary phosphorus (P) restriction on the pathogenesis of secondary hyperparathyroidism (2°HPT) in chronic renal failure (CRF), we studied parathyroid function and parathyroid cell proliferation in 5\\/6 nephrectomized rats (CRF rats) fed with three different dietary P contents (0.6, 0.3 and 0.1%). Four weeks after 5\\/6 nephrectomy, serum immuno-reactive parathyroid hormone (PTH) concentration, PTH

Hung Yi; Masafumi Fukagawa; Hideyuki Yamato; Miki Kumagai; Tsuyoshi Watanabe; Kiyoshi Kurokawa



Increased plasma concentrations of vitamin D metabolites and vitamin D binding protein in women using hormonal contraceptives: a cross-sectional study.  


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

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



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

PubMed Central

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

M?ller, Ulla K.; vi? Streym, Susanna; Jensen, Lars T.; Mosekilde, Leif; Schoenmakers, Inez; Nigdikar, Shailja; Rejnmark, Lars



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

PubMed Central

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



Cinacalcet for Hypercalcemia Caused by Pulmonary Squamous Cell Carcinoma Producing Parathyroid Hormone-Related Peptide  

PubMed Central

Background Current treatments for hypercalcemia caused by lung cell carcinomas producing parathyroid hormone-related peptide (PTH-rp) have limited efficacy, probably because of their lack of effect on PTH-rp secretion. In this case study we explored the efficacy of the calcimimetic cinacalcet as suppressor of PTH-rp production. Patient A 57-year-old male with severe and recurrent hypercalcemia induced by a PTH-rp-producing squamous cell lung carcinoma, stage cT4N3M1b, poorly responding to standard treatments. Results Serum PTH-rp levels were not affected by saline, calcitonin or zoledronate. PTH-rp decreased during chemotherapy and cinacalcet monotherapy. The combination of chemotherapy plus cinacalcet was most effective in rapidly reducing serum calcium and PTH-rp. Conclusion This case study is the first to suggest that cinacalcet may be of value in some cases of PTH-rp-dependent hypercalcemia. Corroborative evidence is needed.

Bech, Anneke; Smolders, Koen; Telting, Darryl; de Boer, Hans



Parathyroid hormone and T-cellular immunity in uremic patients in replacement dialytic therapy.  


We studied 54 patients in replacement dialytic therapy divided into two groups: Group 1, 26 patients with normal parathyroid hormone (PTH) (10-80 pg/ml): and Group 2, 28 patients with elevated PTH (80-400 pg/ml). Total T lymphocytes, CD4, CD8, and CD4/CD8 ratio were evaluated. We found a reduction of total T lymphocytes in both groups compared with controls. A decrease of CD4 and CD4/CD8 ratio with a rise of CD8 occurred in Group 2 but not in Group 1. In Group 2, PTH presented a linear correlation with CD8 and a reverse correlation with total T cells. CD4, and CD4/CD8 ratio. PTH might act on T-cellular immunity with an immunosuppressive effect from the earlier phases of hyperparathyroidism. PMID:8382471

Angelini, D; Carlini, A; Giusti, R; Grassi, R; Mei, E; Fiorini, I; Mazzotta, L; Antonelli, A



Rapid activation of the medullary bone osteoclast cell surface by parathyroid hormone.  


Quantitative transmission electron microscope methods were used to determine the response of functionally inactive avian medullary bone osteoclasts to parathyroid hormone (PTH). Egg-lying Japanese quail were used during a period of the egg cycle when medullary bone was not being resorbed for egg shell calcification and when medullary bone osteoclasts were functionally inactive. Ruffled borders adjacent to bone surfaces were rarely, if ever, found on these cells. 20 min after the administration of PTH, over 70% of the osteoclast profiles had ruffled borders adjacent to bone surfaces. These ruffled borders were bounded by filamentous-rich "clear zones" and resembled ruffled borders found on functionally active cells. There was also a marked increase in plasma calcium levels after PTH administration. This study demonstrates that PTH stimulates the de novo generation of ruffled borders on osteoclasts in vivo and suggests that osteoclasts may be involved in the acute regulation of calcium metabolism by exogenous PTH. PMID:632322

Miller, S C



[Treatment with recombinant parathyroid hormone of advanced osteoporosis--series of cases].  


Osteoporosis is a systemic skeletal disorder characterized by impaired bone strength, leading to an increased risk of fracture. Patients with severe osteoporosis and multiple vertebral fractures are particularly at risk for subsequent osteoporotic fractures independently of antiresorptive therapy. The effective treatment of osteoporosis should prevent fractures through normalization of bone mass and improving bone microarchitecture. Recombinant human parathyroid hormone (teriparatide) is an anabolic (bone forming) agent. The aim of this study was to describe the results of treatment with teriparatide (Forsteo) of three patients with severe osteoporosis. Teriparatide has proved to be effective in preventing bone loss. New osteoporotic fracture has not occurred in two patients. Treatment with teriparatide was safe and well tolerated. PMID:22010479

Skiba, Katarzyna; Adamczak, Marcin; Wiecek, Andrzej



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

PubMed Central

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

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



Enhancement by ethanol of parathyroid-hormone-stimulated cyclic AMP accumulation in isolated renal tubules.  


The effects of ethanol on parathyroid hormone (PTH)-induced increases in adenosine 3':5'-phosphate (cAMP) concentrations were studied in renal cortical tubules of hamsters in vitro. Ethanol concentrations between 0.1 and 3% were found to augment the PTH response in a dose-related way while, concentrations greater than 3% produced a dose-related inhibition of the PTH response. In the absence of PTH, ethanol did not significantly elevate cAMP accumulations at any concentrations tested. In contrast to its effect on intact tubule cells, ethanol did not alter either adenylate cyclase or phosphodiesterase in renal cortical homogenates. Indomethacin, however, produced a concentration-related inhibition of the ethanol-potentiated response without altering the effects of PTH alone. The results suggest a possible involvement of prostaglandins in the potentiating effect of ethanol on the PTH-dependent accumulation of cAMP in renal tubules. PMID:6302464

Biddulph, D M; Wrenn, R W; Currie, M G; Hubbard, W R



Modeling of the parathyroid hormone response after calcium intake in healthy subjects.  


Plasma ionized calcium (Ca(2+)) concentrations are tightly regulated in the body and maintained within a narrow range; thus it is challenging to quantify calcium absorption under normal physiologic conditions. This study aimed to develop a mechanistic model for the parathyroid hormone (PTH) response after calcium intake and indirectly compare the difference in oral calcium absorption from PTH responses. PTH and Ca(2+) concentrations were collected from 24 subjects from a clinical trial performed to evaluate the safety and calcium absorption of Geumjin Thermal Water in comparison with calcium carbonate tablets in healthy subjects. Indirect response models (NONMEM Ver. 7.2.0) were fitted to observed Ca(2+) and PTH data, respectively, in a manner that absorbed but unobserved Ca(2+) inhibits the secretion of PTH. Without notable changes in Ca(2+) levels, PTH responses were modeled and used as a marker for the extent of calcium absorption. PMID:24976761

Ahn, Jae Eun; Jeon, Sangil; Lee, Jongtae; Han, Seunghoon; Yim, Dong-Seok



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

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



Hormonal Relationships to Bone Mass in Elderly Spanish Men as Influenced by Dietary Calcium and Vitamin D  

PubMed Central

We aim to evaluate whether calcium and vitamin D intake is associated with 25-hydroxyvitamin D (25-OH-Vitamin D3) and parathyroid hormone (PTH) serum concentrations or is associated with either the phalangeal dual energy X-ray absorptiometry (pDXA) or the quantitative bone ultrasound (QUS) in independent elderly men. Serum PTH and 25-OH-Vitamin D3 were measured in 195 healthy elderly men (mean age: 73.31 ± 5.10 year). Food intake was quantified using a dietetic scale. Participants with 25-OH-Vitamin D3 levels ? 30 ng/mL (75 nmol/L) and a calcium intake of 800–1200 mg/day exhibited the lowest PTH levels (41.49 ± 16.72 ng/mL). The highest PTH levels (75.60 ± 14.16 ng/mL) were observed in the <30 ng/mL group 25-OH-Vitamin D3 with a calcium intake >1200 mg/day. No significant differences in the serum PTH levels based on the serum 25-OH-Vitamin D3 levels were observed among participants with a calcium intake of 800–1200 mg/day. Serum PTH was inversely correlated with serum 25-OH-Vitamin D3 in the entire patient sample (r = ?0.288, p = 0.019). No differences in any of the three densitometry techniques were observed between any of the age groups in the 800–1200 mg/day and >1200 mg/day calcium intake groups. PTH levels correlate negatively with serum 25-OH-Vitamin D3 levels, and neither calcium nor vitamin D intake exert a strong influence on either of the two parameters.

Moran, Jose M.; Lopez-Arza, Luis Gonzalez; Lavado-Garcia, Jesus M.; Pedrera-Canal, Maria; Rey-Sanchez, Purificacion; Rodriguez-Velasco, Francisco J.; Fernandez, Pilar; Pedrera-Zamorano, Juan D.



Vitamin D status, parathyroid function, bone turnover, and BMD in postmenopausal women with osteoporosis: global perspective.  


Poor vitamin D status is common in the elderly and is associated with bone loss and fractures. The aim was to assess worldwide vitamin D status in postmenopausal women with osteoporosis according to latitude and economic status, in relation to parathyroid function, bone turnover markers, and BMD. The study was performed in 7441 postmenopausal women from 29 countries participating in a clinical trial on bazedoxifene (selective estrogen receptor modulator), with BMD T-score at the femoral neck or lumbar spine 75 nM was 5.9%, 29.4%, 43.5%, and 21.2%, respectively, in winter and 3.0%, 22.2%, 47.2%, and 27.5% in summer. Worldwide, a negative correlation between 25(OH)D and latitude was observed. With increasing 25(OH)D categories of <25, 25-50, 50-75, and >75 nM, mean PTH, OC, and CTX were decreasing (p < 0.001), whereas BMD of all sites was increasing (p < 0.001). A threshold in the positive relationship between 25(OH)D and different BMD parameters was visible at a 25(OH)D level of 50 nM. Our study showed a high prevalence of low 25(OH)D in postmenopausal women with osteoporosis worldwide. Along with latitude, affluence seems to be an important factor for serum 25(OH)D level, especially in Europe, where it is strongly correlated with latitude. PMID:19049341

Kuchuk, Natalia O; van Schoor, Natasja M; Pluijm, Saskia M; Chines, Arkadi; Lips, Paul



Parathyroid hormone depresses cytosolic pH and DNA synthesis in osteoblast-like cells  

SciTech Connect

It has recently become apparent that a number of hormones and growth factors modulate cytosolic pH (pH{sub i}) and there is some evidence that this in turn may influence cell growth. The authors have examined the effects of parathyroid hormone (PTH) on both these parameters in an osteoblast-like cell line, UMR 106. Preliminary studies, using the pH-sensitive fluorescent probe 2{prime},7{prime}-bis(2-carboxyethyl)-5,(6)-carboxyfluorescein indicated that these cells regulate pH{sub i} by means of an amiloride-inhibitable Na{sup +}-H{sup +} exchanger. Rat PTH-(1-34) (rPTH) caused a progressive dose-related decrease in pH{sub i} with a half-maximal effect at 10{sup {minus}11} M. The diacylglycerol analogue, phorbol 12-myristate 13-acetate, increased both pH{sub i} and ({sup 3}H)thymidine incorporation, and amiloride reduced both indexes. However, rPTH remained a potent inhibitor of ({sup 3}H)thymidine incorporation in the presence of amiloride, even though it did not affect pH{sub i} in these circumstances. It is concluded that PTH decreases pH{sub i} and growth in UMR 106 cells but that these changes can be dissociated. Depression of pH{sub i} may have other important effects on bone metabolism, such as reducing cell-cell communication, and may be associated with alkalinization of the bone fluid compartment.

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



Regional myocardial blood flow distribution during intracoronary infusion of parathyroid hormone  

SciTech Connect

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

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



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.

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



Effect of parathyroid hormone on transport by toad and turtle bladder  

SciTech Connect

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

Sabatini, S.; Kurtzman, N.A.



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



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))



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

NASA Astrophysics Data System (ADS)

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

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


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.  


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



Treatment of malignancy-associated hypercalcemia and cachexia with humanized anti-parathyroid hormone-related protein antibody  

Microsoft Academic Search

Parathyroid hormone-related protein (PTHrP) plays a central role in humoral hypercalcemia of malignancy (HHM), which is one of the most frequent paraneoplastic syndromes. PTHrP produced by the tumor acts through a common PTH\\/PTHrP receptor to promote bone resorption, inhibit calcium excretion from the kidney, and induce hypercalcemia. Patients with HHM often develop cachexia associated with typical symptoms such as anorexia,

Koh Sato; Etsuro Onuma; Richard C Yocum; Etsuro Ogata



Elevation of circulating plasma cytokines in cancer patients with high plasma parathyroid hormone-related protein levels  

Microsoft Academic Search

Parathyroid hormone (PTH) and PTH-related protein\\/peptide (PTHrP) bind to the same PTH\\/PTHrP receptor and stimulate osteoblasts to secrete pro-inflammatory cytokines like interleukin (IL)-6. In patients with primary hyperparathyroidism, elevation of plasma levels of tumor necrosis factor (TNF)-? and IL-6 was also described. We, therefore, postulated that PTHrP secreted from cancer cells stimulates the secretion of cytokines and causes increases in

S Takahashi; M Hakuta; K Aiba; Y Ito; N Horikoshi; M Miura; K Hatake; E Ogata



Alkaline phosphatase inhibition by parathyroid hormone and isoproterenol in a clonal rat osteosarcoma cell line. Possible mediation by cyclic AMP  

Microsoft Academic Search

Summary  The effect of parathyroid hormone (PTH 1–34 bovine) on alkaline phosphatase activity was investigated in an osteoblast-like\\u000a clonal cell line derived from rat osteosarcoma (ROS 17\\/2). ROS 17\\/2 alkaline phosphatase resembled the bone enzyme in levamisole\\u000a sensitivity and electrophoretic mobility but differed in heat stability. The specific activity of ROS 17\\/2 alkaline phosphatase\\u000a increased with time in culture. This increase

Robert J. Majeska; Gideon A. Rodan



Three-dimensional Modeling of the Effects of Parathyroid Hormone on Bone Distribution in Lumbar Vertebrae of Ovariectomized Cynomolgus Macaques  

Microsoft Academic Search

:   Biomechanical and quantitative computed tomography (QCT) analyses showed beneficial effects of parathyroid hormone (PTH (1–34))\\u000a on lumbar vertebrae from ovariectomized monkeys, even after withdrawal of treatment for 6 months. Adult cynomolgus monkeys\\u000a were randomized, ovariectomized (except for sham ovariectomy controls), and treated subcutaneously with vehicle (OVX) or 5\\u000a ?g\\/kg per day PTH (1–34) (PTH5) for 18 months. An additional

M. Sato; M. Westmore; J. Clendenon; S. Smith; B. Hannum; G. Q. Zeng; R. Brommage; C. H. Turner



Consequences of Daily Administered Parathyroid Hormone on Myeloma Growth, Bone Disease, and Molecular Profiling of Whole Myelomatous Bone  

Microsoft Academic Search

BackgroundInduction of osteolytic bone lesions in multiple myeloma is caused by an uncoupling of osteoclastic bone resorption and osteoblastic bone formation. Current management of myeloma bone disease is limited to the use of antiresorptive agents such as bisphosphonates.Methodology\\/Principal FindingsWe tested the effects of daily administered parathyroid hormone (PTH) on bone disease and myeloma growth, and we investigated molecular mechanisms by

Angela Pennisi; Wen Ling; Xin Li; Sharmin Khan; Yuping Wang; Bart Barlogie; John D. Shaughnessy; Shmuel Yaccoby; Paul A. Bartell



Plasma Parathyroid Hormone and Insulin Concentrations in Cows Administered Potassium Chloride and Sodium Citrate1*2  

Microsoft Academic Search

Two age groups of nonpregnant cows were used to study plasma changes in parathyroid hormone, insulin, and glucose, and renal clearance rates of magnesium, calcium, and inorganic phosphorus after intraruminal administra tion of 1.5 g potassium chloride (KCl)\\/kg body weight (BW) or 1.5 g sodium citrate\\/kg BW. Magnesium (2.4 mg\\/kg BW) was simultaneously infused intra venously for 120 minutes to



Expression and Role of Parathyroid Hormone-Related Protein in Human Renal Proximal Tubule Cells during Recovery from ATP Depletion  

Microsoft Academic Search

Parathyroid hormone (PTH)-related protein (PTHrP) is widely expressed in normal fetal and adult tissues and regulates growth and differentiation in a number of organ systems. Although various renal cell types produce PTHrP, and PTHrP expression in rat proximal renal tubules is upregulated in response to ischemic injury in vivo, the role of PTHrP in the kidney is unknown. To study




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

SciTech Connect

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

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



Parathyroid hormone stimulates juxtaglomerular cell cAMP accumulation without stimulating renin release  

PubMed Central

Parathyroid hormone (PTH) is positively coupled to the generation of cAMP via its actions on the PTH1R and PTH2R receptors. Renin secretion from juxtaglomerular (JG) cells is stimulated by elevated intracellular cAMP, and every stimulus that increases renin secretion is thought to do so via increasing cAMP. Thus we hypothesized that PTH increases renin release from primary cultures of mouse JG cells by elevating intracellular cAMP via the PTH1R receptor. We found PTH1R, but not PTH2R, mRNA expressed in JG cells. While PTH increased JG cell cAMP content from (log10 means ± SE) 3.27 ± 0.06 to 3.92 ± 0.12 fmol/mg protein (P < 0.001), it did not affect renin release. The PTH1R-specific agonist, parathyroid hormone-related protein (PTHrP), also increased JG cell cAMP from 3.13 ± 0.09 to 3.93 ± 0.09 fmol/mg protein (P < 0.001), again without effect on renin release. PTH2R receptor agonists had no effect on cAMP or renin release. PTHrP increased cAMP in the presence of both low and high extracellular calcium from 3.31 ± 0.17 to 3.83 ± 0.20 fmol/mg protein (P < 0.01) and from 3.29 ± 0.18 to 3.63 ± 0.22 fmol/mg protein (P < 0.05), respectively, with no effect on renin release. PTHrP increased JG cell cAMP in the presence of adenylyl cyclase-V inhibition from 2.85 ± 0.17 to 3.44 ± 0.14 fmol/mg protein (P < 0.001) without affecting renin release. As a positive control, forskolin increased JG cell cAMP from 3.39 ± 0.13 to 4.48 ± 0.07 fmol/mg protein (P < 0.01) and renin release from 2.96 ± 0.10 to 3.29 ± 0.08 ng ANG I·mg prot?1·h?1 (P < 0.01). Thus PTH increases JG cell cAMP via non-calcium-sensitive adenylate cyclases without affecting renin release. These data suggest compartmentalization of cAMP signaling in JG cells.

Atchison, Douglas K.; Harding, Pamela; Cecilia Ortiz-Capisano, M.; Peterson, Edward L.



Effects of Hepatectomy, Nephrectomy, and Nephrectomy/Uremia on the Metabolism of Parathyroid Hormone in the Rat  

PubMed Central

Reports from several laboratories, showing extensive hepatic extraction of circulating parathyroid hormone, led us to examine the effect of near-total hepatectomy on the metabolism of the hormone to circulating fragments, and on its clearance from plasma. The rate of disappearance of 125I-labeled and unlabeled bovine parathyroid hormone from plasma, and the appearance, disappearance, and chemical and immunochemical characteristics of circulating fragments were examined by gel filtration and either sequence-specific radioimmunoassays or sequence analysis using the Edman reaction. Results from awake rats subjected to near-total hepatectomy were compared with those found in sham-treated, nephrectomized, and short-term uremic rats (studied 2 d after nephrectomy). When compared with the sham-treated group, all other groups clear 125I-labeled hormone more slowly; after hepatectomy, however, the clearance rate is most strikingly decreased. After injection of intact hormone, the concentration of carboxy-terminal fragments in the circulation of hepatectomized rats is greatly reduced at all time intervals when compared with that in sham-treated rats. Sequence analysis of plasma samples, collected from rats into which 125I-labeled hormone had been injected, shows that carboxy-terminal fragments having positions 34 and 37 of the intact hormone sequence as their amino-terminal amino acids are abundant in sham-treated, nephrectomized, and nephrectomized/uremic rats, but are undetectable in hepatectomized rats. The data suggest that inasmuch as the liver in vivo generates most of the carboxy-terminal fragments resulting from the metabolism of injected hormone, specific cell types within the liver must be the principal locus of the responsible enzyme(s); thus, studies of the enzymic properties of isolated hepatic cells in vitro most likely will yield information of physiologic relevance to the metabolism of the hormone in the intact animal.

Segre, Gino V.; D'Amour, Pierre; Hultman, Anne; Potts, John T.



Intraoperative serum parathyroid hormone level is an indicator of hypocalcaemia in total thyroidectomy patients.  


Postoperative hypocalcaemia is the most frequent and common complication after total thyroidectomy. It is necessary to diagnose or to predict hypocalcaemia immediately after total thyroidectomy for minimizing complications. A prospective observational study was carried out in the Department of Clinical Pathology in collaboration with Department of Microbiology & Immunology, Department of Surgery, Department of Otolaryngology, Bangabandhu Sheikh Mujib Medical University (BSMMU) and Department of Otolaryngology, Dhaka Medical College & Hospital (DMC&H), Dhaka, during the period of September 2010 to August 2011 to evaluate intraoperative (20 minutes after total thyroidectomy) parathyroid hormone (PTH) measurement as a predictor of post thyroidectomy hypocalcaemia. Total 65 patients were enrolled in this study those came for total thyroidectomy. Postoperative hypocalcaemia developed in 25 cases. Intraoperative PTH was assessed and significant correlation was found between intraoperative PTH level and development of hypocalcaemia. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value of intraoperative serum PTH for prediction of post total thyroidectomy hypocalcaemia were 84.0%, 85.0%, 84.6%, 77.8%, and 89.5% respectively. Because of the high sensitivity, specificity and accuracy of intraoperative serum PTH of this study, the early prediction of hypocalcaemia could be made by single assay of intraoperative serum PTH level at 20 minutes after total thyroidectomy. PMID:23540182

Islam, M S; Sultana, T; Paul, D; Huq, A H M Z; Chowdhury, A A; Ferdous, C; Ahmed, A N N



Association between Parathyroid Hormone Levels and Inflammatory Markers among US Adults  

PubMed Central

Background and Aims. High levels of parathyroid hormone (PTH) appear to be associated with an increased mortality. Previous studies concerning the relationship of inflammatory markers with hyperparathyroidism have yielded inconsistent results. This study investigated whether serum PTH concentrations were independently associated with several inflammatory markers among the US adults. Materials and Methods. Using data from the National Health and Nutrition Examination Survey, we examined the relation between serum PTH and C-reactive protein (CRP), red cell distribution width (RDW), and platelet-to-lymphocyte ratio (PLR) levels with weighted linear regression. Additionally, we examined the relation with increased modified Glasgow Prognostic Score (mGPS) by using weighted logistic regression. Results. CRP, RDW, and PLR values increased with increasing serum PTH concentration. After extensively adjusting for covariates, CRP and RDW increased linearly and across PTH categories (all P < 0.001), while PLR marginally increased (P = 0.190 and P = 0.095 using PTH as a categorical and continuous variable, resp.). The odds ratio of increased mGPS was 1.11 and 1.31 across PTH categories and with increasing PTH levels continuously. Conclusion. These nationally representative data indicate that serum PTH levels are independently associated with several inflammatory markers in the US population. The casual relationship between PTH levels and inflammation remains to be elucidated.

Cheng, Shih-Ping; Liu, Chien-Liang; Liu, Tsang-Pai; Hsu, Yi-Chiung; Lee, Jie-Jen



Parathyroid hormone increases cytosolic calcium in neonatal nephron through protein kinase C pathway.  


In mammals, neonatal positive calcium balance is required for adequate growth. Parathyroid hormone (PTH) plays a central role in this process mainly through its action on the distal nephron. We studied the effect of PTH on cytosolic calcium in distal segments from neonatal rat kidney. PTH elicited a concentration-dependent increase in cytosolic calcium in neonatal distal nephron (EC(50)=0.5 nM) but not in proximal tubules. At similar PTH concentrations the response was higher in the neonatal than in the adult tubules. The response was associated with protein kinase C (PKC), since phorbol myristate acetate (100 nM) increased [Ca(2+)]i, and staurosporin, an inhibitor of PKC, decreased (10 nM) or suppressed (100 nM) the PTH effect. cAMP analogues did not change [Ca(2+)]i. The response was diminished in low external calcium (0.1 mM) and absent at zero calcium, indicating dependency on external calcium. Resting calcium decreased from 80+/-10.8 to 28.6+/-2.6 nM at zero [Ca(2+)]e. PTH and nifedipine increased cytosolic calcium in an additive fashion. We show for the first time that PTH increased cytosolic calcium in the distal nephron of neonatal kidney, in a concentration-dependent pattern and in association with PKC activation. Higher sensitivity of the neonatal tubule might facilitate absorption of this cation during the neonatal period, when growth requires a positive balance of calcium. PMID:15300474

Valencia, Laura; Melendez, Estela; Namorado, María C; Martin, Dolores; Bidet, Michel; Poujeol, Philippe; Reyes, Jose L



Combined hepatocellular-cholangiocarcinoma producing parathyroid hormone-related protein: report of a case.  


Combined hepatocellular-cholangiocarcinoma (CHCC) is an uncommon form of primary liver cancer. A 57-year-old man was readmitted to our hospital for treatment of recurrent CHCC, 12 months after central bisegmentectomy and 4 months after limited hepatic resection. Magnetic resonance imaging (MRI) revealed multiple hepatic nodules. Laboratory data showed increased serum levels of ?-fetoprotein (AFP), calcium, and parathyroid hormone-related protein (PTH-rP), to 5,571 ng/mL, 17.0 mg/dL, and 16.1 pmol/L, respectively. Palliative mass reduction surgery was indicated by the fact that the hypercalcemia was difficult to manage medically. Thus, we performed lateral segmentectomy with partial resection of segment 7 and the caudate lobe, and microwave coagulation therapy for multiple recurrent CHCC. Thereafter, the serum PTH-rP and AFP levels decreased remarkably and the hypercalcemia was controlled for the next 3 months. He died of disease progression 9 months after the last hepatic surgery. To our knowledge, this is only the second reported case of CHCC producing PTH-rP in the English-language literature. PMID:24013836

Matsumoto, Michinori; Wakiyama, Shigeki; Shiba, Hiroaki; Gocho, Takeshi; Misawa, Takeyuki; Ishida, Yuichi; Itsubo, Mariko; Suzuki, Masafumi; Yanaga, Katsuhiko



The effect of endogenous parathyroid hormone in iliac bone structure and turnover in healthy postmenopausal women.  


Little is known about the effect of endogenous parathyroid hormone (PTH) on the skeleton in postmenopausal women without hyperparathyroidism. In this study, the effects of PTH on bone were investigated in iliac crest biopsies obtained from 37 healthy white postmenopausal women aged 50-73 years. The results showed that neither cancellous nor cortical bone structure changed with serum PTH levels. In cancellous bone, bone formation (wall thickness, osteoid surface, osteoblast surface, mineralizing surface, and mineral apposition rate) and turnover (bone formation rate at the surface, volume levels, and activation frequency) variables increased with increasing serum PTH levels (all p < 0.05) in univariate analysis. Multiple linear regressions, adjusted for serum 25-OHD, calcium, alkaline phosphatase, age, and BMI, showed that serum PTH level was independently associated with wall thickness, osteoid surface, osteoblast surface, mineralizing surface, and bone formation rate (all p < 0.05). In cortical bone, no histomorphometric variable was correlated with PTH levels. On the endosteal surface, some of the bone formation (osteoid surface, osteoblast surface, mineralizing surface) and turnover (bone formation rate at the bone surface levels and activation frequency) variables were positively correlated with PTH levels (all p < 0.05). None of these variables could be independently predicted by PTH status. We conclude that in healthy postmenopausal women endogenous PTH has a positive effect on bone formation on the cancellous surface. The effects of PTH on the endosteal surface are probably confounded by other factors. PMID:23842963

Rao, D Sudhaker; Parikh, Nayana; Palnitkar, Saroj; Qiu, Shijing



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.



Osteal macrophages support physiologic skeletal remodeling and anabolic actions of parathyroid hormone in bone.  


Cellular subpopulations in the bone marrow play distinct and unexplored functions in skeletal homeostasis. This study delineated a unique role of osteal macrophages in bone and parathyroid hormone (PTH)-dependent bone anabolism using murine models of targeted myeloid-lineage cell ablation. Depletion of c-fms(+) myeloid lineage cells [via administration of AP20187 in the macrophage Fas-induced apoptosis (MAFIA) mouse model] reduced cortical and trabecular bone mass and attenuated PTH-induced trabecular bone anabolism, supporting the positive function of macrophages in bone homeostasis. Interestingly, using a clodronate liposome model with targeted depletion of mature phagocytic macrophages an opposite effect was found with increased trabecular bone mass and increased PTH-induced anabolism. Apoptotic cells were more numerous in MAFIA versus clodronate-treated mice and flow cytometric analyses of myeloid lineage cells in the bone marrow showed that MAFIA mice had reduced CD68(+) cells, whereas clodronate liposome-treated mice had increased CD68(+) and CD163(+) cells. Clodronate liposomes increased efferocytosis (clearance of apoptotic cells) and gene expression associated with alternatively activated M2 macrophages as well as expression of genes associated with bone formation including Wnt3a, Wnt10b, and Tgfb1. Taken together, depletion of early lineage macrophages resulted in osteopenia with blunted effects of PTH anabolic actions, whereas depletion of differentiated macrophages promoted apoptotic cell clearance and transformed the bone marrow to an osteogenic environment with enhanced PTH anabolism. These data highlight a unique function for osteal macrophages in skeletal homeostasis. PMID:24406853

Cho, Sun Wook; Soki, Fabiana N; Koh, Amy J; Eber, Matthew R; Entezami, Payam; Park, Serk In; van Rooijen, Nico; McCauley, Laurie K



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.



Full length parathyroid hormone (1-84) in the treatment of osteoporosis in postmenopausal women  

PubMed Central

Objective: To review the pharmacological properties and the available clinical data of full length parathyroid hormone (PTH) in post-menopausal osteoporosis. Sources: A MEDLINE search was completed, together with a review of information obtained from the manufacturer and from the medicine regulatory agencies. Study and data selection: Studies were selected according to relevance and availability. Relevant information (design, objectives, patients’ characteristics, outcomes, adverse events, dosing, etc) was analyzed. Results: Different studies have shown that, when administered intermittently as a subcutaneous injection in the abdomen, PTH increases bone mineral density (BMD) and prevents vertebral fractures. On completion of PTH therapy (up to 24 months), there is evidence that sequential treatment with alendronate is associated with a therapeutic benefit in terms of increase in BMD. Further trials are necessary to determine long-term safety and the role of PTH in combination with other treatments for osteoporosis and the effect of repeated cycles of PTH followed by an anti-catabolic agent. There are currently no completed comparative trials with other osteoporosis treatments. Conclusions: Full length PTH, given intermittently as an abdominal subcutaneous injection, appears to be a safe and efficacious treatment option for high risk osteoporosis. More data are needed to determine its specific role in osteoporosis treatment.

Jodar-Gimeno, Esteban



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



Ectopic secretion of parathyroid hormone in a neuroendocrine tumor: a case report and review of the literature  

PubMed Central

Very few cases have been reported in which the production and secretion of intact PTH by a non-parathyroid tumor has been authenticated. This paper describes the case of a 73 year old white female with a clinical and biochemical profile characteristic of primary hyperparathyroidism. Sestamibi scan and comprehensive neck ultrasono-graphy failed to localize a cervical lesion. Because the clinical manifestations were striking, neck exploration was performed. Dissection of the central compartment identified a lesion. PTH levels dropped to normal within ten minutes after its removal. Intraoperative parathyroid hormone assays facilitated the successful surgical removal of the lesion. Pathological examination yielded a diagnosis of a neuroendocrine tumor. These results document the ectopic production of intact PTH by a neuroendocrine tumor and present a novel neoplastic cause of primary hyperparathyroidism. This is the second report of an ectopic neuroendocrine tumor in the head and neck which secreted intact PTH.

Kandil, Emad; Noureldine, Salem; Khalek, Mohamed Abdel; Daroca, Philip; Friedlander, Paul



Stimulation of ovine placental calcium transport by purified natural and recombinant parathyroid hormone-related protein (PTHrP) preparations.  


Perfusion in situ of the placenta of previously thyroparathyroidectomized fetal lambs has been used to compare the ability of various forms of parathyroid hormone-related protein (PTHrP) to stimulate placental calcium transport. Whereas PTHrP (1-34) was without effect, PTHrP (1-141) was active but usually after a delay of up to 1 h, in common with the effect noted when using extracts of fetal parathyroid glands. In contrast, PTHrP (1-84) and PTHrP (1-108), tended to show a more rapid stimulatory action. It is suggested that post-translational processing of PTHrP (1-141) may occur as an activating step in the placenta in vivo. PMID:2798763

Abbas, S K; Pickard, D W; Rodda, C P; Heath, J A; Hammonds, R G; Wood, W I; Caple, I W; Martin, T J; Care, A D



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.



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

PubMed Central

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

Tillmann, Frank-Peter; Hofen, Daniela; Herten, Monika; Krauspe, Rudiger; Jager, Marcus



Systemic intermittent parathyroid hormone treatment improves osseointegration of press-fit inserted implants in cancellous bone  

PubMed Central

Background and purpose Intermittent administration of parathyroid hormone (PTH) has an anabolic effect on bone, as confirmed in human osteoporosis studies, distraction osteogenesis, and fracture healing. PTH in rat models leads to improved fixation of implants in low-density bone or screw insertion transcortically. Material and methods We examined the effect of human PTH (1–34) on the cancellous osseointegration of unloaded implants inserted press-fit in intact bone of higher animal species. 20 dogs were randomized to treatment with human PTH (1–34), 5 ?g/kg/day subcutaneously, or placebo for 4 weeks starting on the day after insertion of a cylindrical porous coated plasma-sprayed titanium alloy implant in the proximal metaphyseal cancellous bone of tibia. Osseointegration was evaluated by histomorphometry and fixation by push-out test to failure. Results Surface fraction of woven bone at the implant interface was statistically significantly higher in the PTH group by 1.4 fold with (median (interquartile range) 15% (13–18)) in the PTH group and 11% (7–13) in control. The fraction of lamellar bone was unaltered. No significant difference in bone or fibrous tissue was observed in the circumferential regions of 0–500, 500–1,000, and 1,000–2,000 ?m around the implant. Mechanically, the implants treated with PTH showed no significant differences in total energy absorption, maximum shear stiffness, or maximum shear strength. Interpretation Intermittent treatment with PTH (1–34) improved xhistological osseointegration of a prosthesis inserted press-fit at surgery in cancellous bone, with no additional improvement of the initial mechanical fixation at this time point.



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

SciTech Connect

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

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



Immunologic disturbances and levels of parathyroid hormone in uremic patients in replacement dialysis therapy.  


We studied the changes in cellular immunity in patients in replacement dialysis therapy (RDT) and examined the relationship between T-lymphocyte function and plasma levels of parathyroid hormone (PTH). In a preliminary study we found that increased plasma levels of PTH were associated with a decrease of T-lymphocytes and CD4, an increase in CD8 and a reduction in the ratio of CD4 to CD8. In the present study we examined the relationship between plasma levels of PTH, interleukin 2 receptors (IL-2R) and soluble human CD8 (S-CD8). We studied 54 patients divided into two groups: 26 patients with normal levels of PTH and 28 patients with increased levels of PTH. We found a significant reduction in total T-lymphocytes in both groups as compared to controls, with an inverse correlation between total T-lymphocytes and plasma PTH in the second group (R = -0.52). There was an increase in IL-2R in the group II as compared to the controls and also in the total population of uremic patients with a linear correlation between levels of IL-2R and PTH (R = 0.6). The levels of S-CD8 showed a significant increase in both groups with a linear correlation between levels of SC-D8 and PTH (R = 0.63). No specific differences were seen between patients treated with and without 1,25-dihydroxyvitamin D3. The elevated levels of PTH affect the lymphocyte function and are associated with change in cellular immunity with reduction in total number of T cells, and increases in levels of CD8, S-CD8 and IL-2R. PMID:7834917

Angelini, D; Carlini, A; Mazzotta, L; Mei, E; Grassi, R; Giusti, R; Neri, M; Fiorini, I; Antonelli, A



Parathyroid hormone inhibition of vasopressin-induced vascular smooth muscle contraction.  


In various cells, parathyroid hormone (PTH) has been shown to initiate both polyphosphoinositide (PI) breakdown and activation of adenylate cyclase (AC). In vascular smooth muscle cells (VSMC), PI hydrolysis is known to induce contraction, whereas a rise in adenosine 3',5'-cyclic monophosphate (cAMP) causes relaxation. In the present study, the effect of PTH on arginine vasopressin (AVP)-induced VSMC contraction and signal transduction was studied. PTH (10(-7) M) attenuated the percentage of VSMC contracting in response to AVP (10(-7) M; 40 to 26.5%, P < 0.05). This loss of VSMC contractility was not the result of PTH-induced changes in AVP receptor binding. PTH did, however, stimulate VSMC cAMP production in a dose-dependent manner. The effect of PTH on AVP-induced contraction could be mimicked by treating VSMC with the cell-permeant cAMP analogue, 8-(4-chlorophenylthio)-cAMP (ClPheScAMP). The effect of PTH on AVP-induced VSMC contraction was blocked by H-8, an inhibitor of protein kinase A and thus cAMP production. In parallel to the inhibitory effects of ClPheScAMP on VSMC contraction, AVP-stimulated inositol trisphosphate production was also reduced by this permeant cAMP (4,415 to 2,592 cpm/mg protein, P < 0.01). PTH-induced production of cAMP was not blocked by an inhibition of prostaglandin synthesis [PTH 203 vs. PTH + ibuprofen 161 fmol/micrograms protein, not significant (NS)]. In contrast, AVP also stimulated cAMP, but this increase was blocked by ibuprofen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8384413

Wang, X; Briner, V A; Schrier, R W



Maternal absence of the parathyroid-hormone 2 (PTH2) receptor affects postnatal pup development  

PubMed Central

During the lactation period mothers have a variety of adaptive changes in brain physiology and behaviour to allow them to properly raise their pups. The exact circuitries and mechanisms responsible for these changes are not fully understood. Recent evidence suggests that the neuropeptide tuberoinfundibular peptide of 39 residues (TIP39) and its receptor, the parathyroid-hormone 2 receptor (PTH2-R), contribute to these mechanisms. To further investigate this idea we evaluated the growth rate of pups from dams with a non-functional PTH2-R (PTH2-R-KO) as well as maternal behavioural and neuroendocrine parameters. We observed that PTH2-R-KO-reared pups had a slowed growth rate. This was associated with a reduced volume of milk yielded by PTH2-R-KO dams after 30-min suckling when compared with wild-type dams (WT) when pups were returned after five hours separation. Our data suggests a reduced sensitivity of PTH2-R-KO dams to pup stimulation. We also observed a significant reduction in suckling-induced c-Fos expression in the paraventricular nucleus of the hypothalamus and signs of lower prolactin levels in the PTH2-R-KO dams. Our data suggest that the reduced growth rate of PTH2-R-KO-reared pups was likely the result of alterations in the milk-production pathway rather than modifications in behaviour. Although PTH2-R-KO dams showed increased anxiety in the elevated zero-maze test, no differences from WT dams in maternal behaviour were observed. Altogether, our findings suggest involvement of the TIP39/PTH2-R system in the pathways involved in the successful development of the pups.

Coutellier, Laurence; Logemann, Allison; Rusnak, Milan; Usdin, Ted B.



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

PubMed Central

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

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



Morphological and ultrastructural aspects of the activation of avian medullary bone osteoclasts by parathyroid hormone.  


The activation of physiologically inactive medullary bone osteoclasts by parathyroid hormone (PTH) was examined using light and electron microscopy and histomorphometric methods. Medullary bone osteoclasts are functionally inactive during the avian egg-laying cycle when an egg shell is not being calcified in the shell gland. Japanese quail hens were given 0.5 IU/g PTH and the medullary bone osteoclasts were examined up to 90 min later. Administration of PTH results in rapid changes in osteoclast morphology and ultrastructure. Within 10 min ectoplasmic regions containing condensed-appearing material are evident in areas of the cell adjacent to bone surfaces. In tannic acid-fixed specimens, these ectoplasmic regions contain bundles of filaments extending perpendicularly from the osteoclast plasma membrane into the cytoplasm. It is in these areas that ruffled border development is initiated. Even at 10 min after PTH administration, mineral crystals are seen between the developing cell surface invaginations and folds. By 15 min after PTH administration, ruffled borders have appeared next to bone surfaces. The rapid development of ruffled borders on medullary bone osteoclasts after PTH is confirmed by electron microscope histomorphometry. By 30 min after PTH administration, ruffled borders are well developed and large endocytic vacuoles are beginning to appear in the osteoclast cytoplasm. Light microscope histomorphometric measurements indicate that osteoclasts are also increasing in size and spreading along bone surfaces with time after PTH administration. This study provides a morphologic and ultrastructural description of osteoclast activation by PTH. The results indicate that osteoclasts may effect rapid changes in bone resorption and mineral metabolism due to exogenous PTH in hens. PMID:6703339

Miller, S C; Bowman, B M; Myers, R L



A closer look at the immediate trabecula response to combined parathyroid hormone and alendronate treatment.  


Daily injections of parathyroid hormone (PTH) are the only FDA-approved anabolic treatment for osteoporosis; however PTH is only clinically approved for treatment periods of up to 24months. To enhance its anabolic effect, combining PTH with anti-resorptive therapy was proposed and expected to maximize the effectiveness of PTH. The current study aimed to elucidate structural mechanisms through which combination therapy can further improve bone strength over a limited treatment window of 12days, to more closely examine the early phase of the anabolic window. We examined 30 female rats treated with either vehicle (Veh), alendronate (ALN), PTH, or both PTH and ALN (PTH+ALN). Standard and individual trabecula segmentation (ITS)-based microstructural analyses were performed using in vivo micro-computed tomography. We found an increase in BV/TV in all treatments with the highest in the PTH+ALN group. Tb.Th* increased in both PTH and PTH+ALN groups well beyond that of the Veh or ALN group. SMI decreased in all treatments with PTH+ALN having the greatest tendency toward plate-like structures. ITS confirmed the trend toward more plate-like structures with increased plate Tb.N* and increased plate-to-rod ratio that was most pronounced in the PTH+ALN group. Using image-based finite element analysis, we demonstrated that stiffness increased in all treatment groups, again with the largest increase in the PTH+ALN group, indicating the resulting structural implications of increased plate-like structure. Static and dynamic bone histomorphometry and a serum resorption marker confirmed that PTH+ALN significantly increased bone formation activities and suppressed bone resorption activities. Overall the results indicate that PTH+ALN treatment has an additive effect due to a preferential increase in plate-like structures. PMID:24468717

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



Effects of parathyroid hormone on cyclic-AMP concentrations of in vitro Necturus maculosus gastric antrum.  


The effects of bovine parathyroid hormone (bPTH1-84) on the stimulation of intracellular cyclic-AMP [cAMP] were investigated in an in vitro preparation of Necturus maculosus antral mucosa. When the antrum was exposed to 1, 5, 10, or 100 nM bPTH1-84, there was an approximately 2-fold nonlinear increase in tissue [cAMP] over basal values. The pretreatment of the antral mucosa with 1 mM isobutylmethylxanthine (IBMX, a phosphodiesterase inhibitor) increased with detectability of mucosal [cAMP]. The addition of 1, 5, 10, or 100 nM bPTH1-84 to tissues pretreated with IBMX resulted in an approximately 3.5-fold linear increase in mucosal [cAMP] over basal values. The time course of the generation of mucosal cAMP to 10 nM bPTH1-84 resulted in a small but significant transient increase at 2.5 min after the addition of bPTH1-84 but no change in the medium [cAMP]. In tissues pretreated with 1 mM IBMX the response to 10 nM bPTH1-84 was a large biphasic increase of [cAMP] at 2.5 min that progressively declined to near basal values by 15 min. There was also a significant sustained increase in the [cAMP] in the bathing medium at 2.5 min of tissues pretreated with IBMX followed by 10 nM bPTH1-84. These results suggest the presence of an adenylate cyclase that can be activated by a mammalian bPTH1-84 in elevating intracellular cAMP levels in the N. maculosus antral mucosa. PMID:2478416

Rutten, M J; Chern, H T; Moore, C D; Hamilton, J; Cheung, L Y



Sampling and storage conditions influencing the measurement of parathyroid hormone in blood samples: a systematic review.  


Parathyroid hormone (PTH) is relatively unstable: optimisation of pre-analytical conditions, including specimen type, sampling time and storage conditions, is essential. We have undertaken a systematic review of these pre-analytical conditions. An electronic search of the PubMed, Embase, Cochrane, Centre for Research and Dissemination and Bandolier databases was undertaken. Of 5511 papers identified, 96 underwent full text review, of which 83 were finally included. At room temperature PTH was stable in ethylenediaminetetraacetic acid (EDTA) preserved whole blood for at least 24 h and in EDTA plasma for at least 48 h after venepuncture. Losses were observed in clotted blood samples after 3 h and in serum after 2 h. At 4°C PTH was more stable in EDTA plasma (at least 72 h) than serum (at least 24 h). Central venous PTH concentrations were higher than peripheral venous concentrations. In the northern hemisphere, PTH concentrations were higher in winter than summer. PTH has a circadian rhythm characterised by a nocturnal acrophase and mid-morning nadir. Data related to frozen storage of PTH (-20°C and -80°C) were limited and contradictory. We recommend that blood samples for PTH measurement should be taken into tubes containing EDTA, ideally between 10:00 and 16:00, and plasma separated within 24 h of venepuncture. Plasma samples should be stored at 4°C and analysed within 72 h of venepuncture. Particular regard must be paid to the venepuncture site when interpreting PTH concentration. Further research is required to clarify the suitability of freezing samples prior to PTH measurement. PMID:24072573

Hanon, Elodie A; Sturgeon, Catharine M; Lamb, Edmund J



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:; Aghaloo, Tara L. [Division of Diagnostic and Surgical Sciences, UCLA School of Dentistry, Los Angeles, CA 90095 (United States)]. E-mail:; Bezouglaia, Olga [Division of Diagnostic and Surgical Sciences, UCLA School of Dentistry, Los Angeles, CA 90095 (United States)]. E-mail:; Nervina, Jeanne M. [Section of Orthodontics, UCLA School of Dentistry, Los Angeles, CA 90095 (United States)]. E-mail:; 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:



Ethnic differences in parathyroid hormone secretion and mineral metabolism in response to oral phosphate administration  

PubMed Central

Ethnic differences in bone metabolism have been reported and it has been suggested that these may be partly due to prolonged exposure to an elevated plasma parathyroid hormone (PTH) concentration or a decreased sensitivity to PTH. We explored ethnic differences in bone and mineral metabolism by 5 days of oral phosphate (P) loading to stimulate PTH secretion. Healthy older people from UK (B), The Gambia (G) and China (C), 15 individuals from each sex and ethnic group, were studied. Blood and urine samples were collected before and 2 h after P dose on days 1, 4 and 5 and on a control day. The induced changes (%) in PTH and markers of mineral and bone metabolism after 2 h and over 5 days were examined. At baseline, PTH, 1,25(OH)2D and bone turnover markers were higher in Gambian subjects than in British and Chinese subjects (P ? 0.01). 2 h after P loading, ionized calcium (iCa) decreased and PTH and plasma P (P) increased in all groups (P ? 0.01, n.s. between groups). Urinary P to creatinine ratio (uP/Cr) increased, the increase being greater in Chinese subjects than in British and Gambian subjects on days 4 and 5 (P ? 0.01). By day 5, fasting iCa was decreased and P increased in British and Gambian (P ? 0.01) but not in Chinese subjects. Fasting PTH and uP/Cr increased in all groups. There were ethnic differences in changes in bone markers, but the relationship with changes in PTH was comparable between groups. In conclusion, ethnic differences in mineral metabolism in response to 5-day P loading were found. Chinese subjects showed a more rapid renal clearance of P than British and Gambian counterparts and there were differences between the groups in the skeletal response to P loading, but no evidence was found for resistance to the resorbing effects of PTH.

Yan, Liya; Schoenmakers, Inez; Zhou, Bo; Jarjou, Landing M.; Smith, Emily; Nigdikar, Shailja; Goldberg, Gail R.; Prentice, Ann



Parathyroid hormone related-protein promotes epithelial-to-mesenchymal transition in prostate cancer.  


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

Ongkeko, Weg M; Burton, Doug; Kiang, Alan; Abhold, Eric; Kuo, Selena Z; Rahimy, Elham; Yang, Meng; Hoffman, Robert M; Wang-Rodriguez, Jessica; Deftos, Leonard J



Structure-function relationship of the nuclear localization signal sequence of parathyroid hormone-related protein.  


Parathyroid hormone-related protein (PTHrP) contains a nuclear localization signal (NLS) sequence within 87-107. NLS sequences are generally capable of penetrating cellular membranes due to a richness of basic amino acid residues, and thus have been used as cell-penetrating peptides (CPPs) to translocate biologically active peptides/proteins into cells. The NLS sequence of PTHrP is not exception to this finding; however, PTHrP(87-107) contains 2 acidic glutamate residues at 99 and 101 within the basic amino acid stretch, which is not commonly observed in other CPPs such as HIV-1 Tat(48-60). In this study, we indicated structure-function relationship of the PTHrP NLS to understand the effect of acidic glutamate residues on cell permeability and intracellular localization. We chemically synthesized PTHrP(87-107) and its N-terminally truncated analogues. Their intracellular localization pattern was analyzed by microscopy, radioimmunoassay, and fluorescence-activated cell sorting. Although all analogues were translocated into cells, internalization by the cytoplasm and/or nucleus was length-dependent; specifically, PTHrP(97-107), PTHrP(95-107), and PTHrP(93-107) were more frequently localized in the cytoplasm. We assume that reduction in the net positive charge within PTHrP NLS analogues resulted in increased cytoplasm- translocation activity. We propose that PTHrP(97-107) is a useful carrier peptide for delivery and expression of cargo molecules in the cytoplasm. PMID:22790219

Ohshima, Keiichic; Takeda, Sachiyo; Hirose, Mariko; Akiyama, Yasuto; Iguchi, Kazuaki; Hoshino, Minoru; Yamaguchi, Ken; Mochizuki, Tohru



Interleukin-6 enhances hypercalcemia and bone resorption mediated by parathyroid hormone-related protein in vivo.  

PubMed Central

Tumors frequently induce the multifunctional cytokine IL-6, which has been linked to several paraneoplastic syndromes, most notably cachexia. IL-6 stimulates osteoclast formation, causes mild hypercalcemia, and is produced by bone cells in vitro upon exposure to systemic hormones. Since IL-6 is produced together with parathyroid hormone-related protein (PTH-rP) in some patients with cancer, we tested the hypothesis that production of IL-6 potentiates the effects of PTH-rP on Ca2+ homeostasis and osteoclastic bone resorption and examined potential mechanisms for these interactions in vivo. Chinese hamster ovarian (CHO) cells stably transfected with cDNAs for IL-6 (CHO/IL-6) and PTH-rP sense (CHO/PTH-rP) or antisense (CHO/PTH-rP AS) were inoculated intramuscularly into nude mice. Experimental groups included CHO/IL-6 plus CHO/PTH-rP; CHO/IL-6 plus CHO/PTH-rP AS; CHO/IL-6 alone; and CHO/PTH-rP alone. Blood ionized Ca2+ was measured on days 0, 7, 10, 12, and 13. Three different developmental stages in the osteoclast lineage were examined at day 13: the early multipotential precursor, granulocyte macrophage colony-forming units (CFU-GM); more mature mononuclear osteoclast precursors, assessed by their capacity to form tartrate-resistant acid phosphatase-positive multinucleated cells in marrow cultures; and mature osteoclasts, assessed by histomorphometry. IL-6 increased CFU-GM but not bone resorption or Ca2+. In contrast, PTH-rP induced hypercalcemia and bone resorption and increased multinucleated osteoclasts and more mature precursors cells, but not CFU-GM. However, mice treated with both IL-6 and PTH-rP had very marked hypercalcemia and osteoclastosis as well as an increase in the number of both CFU-GM and mature osteoclast precursors. These data demonstrate that IL-6 enhances PTH-rP-mediated hypercalcemia and bone resorption, most likely by increasing the pool of early osteoclast precursors that in turn can differentiate to mature osteoclasts. We conclude that IL-6 stimulatory effects on osteoclast precursors may enhance the effects of other bone resorption factors that act at later stages in the osteoclast lineage. Images

de la Mata, J; Uy, H L; Guise, T A; Story, B; Boyce, B F; Mundy, G R; Roodman, G D



The Interleukin6\\/Soluble Interleukin6 Receptor System Induces Parathyroid Hormone–Related Protein in Human Osteoblastic Cells  

Microsoft Academic Search

In the present in vitro study, we tested the hypothesis that parathyroid hormone-related protein (PTHrP) might be a mediator of interleukin-6 (IL-6) and its soluble receptor (IL-6sR) in osteoblasts. We found that IL-6, within 1–20 ng\\/mL, added together with IL-6sR (100 ng\\/mL), rapidly (1 hour) increased PTHrP mRNA in human osteoblastic osteosarcoma MG-63 cells and human osteoblastic (hOB) cells from trabecular bone.

C. Guillén; A. R. de Gortázar; P. Esbrit



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)



Regulation of PTH secretion by 25-hydroxyvitamin D and ionized calcium depends on vitamin D status: A study in a large cohort of healthy subjects  

Microsoft Academic Search

IntroductionPrevious papers investigating vitamin D status have often outlined the significant relationships between serum parathyroid hormone (PTH) and 25-hydroxyvitamin D (25OHD), but the influence of ionized calcium levels has not been concomitantly considered.

Vincenzo Carnevale; Luciano Nieddu; Elisabetta Romagnoli; Claudia Battista; Maria Lucia Mascia; Iacopo Chiodini; Cristina Eller-Vainicher; Vincenzo Frusciante; Stefano Angelo Santini; Michele La Porta; Salvatore Minisola; Alfredo Scillitani



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

Microsoft Academic Search

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

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




Microsoft Academic Search

The concept of a hormone-resistant disease has been introduced around the 1940's by Fuller Albright by studying the rickets resistant to vitamin D therapy. He called the disease pseudohypoparathyroidism, as the patients howed clinical features of hypoparathyroidism, but the injection of parathyroid hormone was not followed by the expected increases of serum calcium levels and urinary phosphate excretion. Thus, the



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.




Biasing the parathyroid hormone receptor: relating in vitro ligand efficacy to in vivo biological activity.  


Recent advances in our understanding of the pluridimensional nature of GPCR signaling have provided new insights into how orthosteric ligands regulate receptors, and how the phenomenon of functional selectivity or ligand "bias" might be exploited in pharmaceutical design. In contrast to the predictions of simple two-state models of GPCR function, where ligands affect all aspects of GPCR signaling proportionally, current models assume that receptors exist in multiple "active" conformations that differ in their ability to couple to different downstream effectors, and that structurally distinct ligands can bias signaling by preferentially stabilizing different active states. The type 1 parathyroid hormone receptor (PTH(1)R) offers unique insight into both the opportunities and challenges of exploiting ligand bias in pharmaceutical design, not only because numerous "biased" PTH analogs have been described but also because many of them have been characterized for biological activity in vivo. The PTH(1)R has pleiotropic signaling capacity, coupling to G(s), G(q/11), and G(i/o) family heterotrimeric G proteins, and binding arrestins, which mediate receptor desensitization and arrestin-dependent signaling. Here, we compare the activity of six different PTH(1)R ligands in a common HEK293 cell background using three readouts of receptor activation, cAMP production, intracellular calcium influx, and ERK1/2 activation, demonstrating the range of signal bias that can be experimentally observed in a "typical" screening program. When the in vitro activity profiles of these ligands are compared to their reported effects on bone mass in murine models, it is apparent that ligands activating cAMP production produce an anabolic response that does not correlate with the ability to also elicit calcium signaling. Paradoxically, one ligand that exhibits inverse agonism for cAMP production and arrestin-dependent ERK1/2 activation in vitro, (D-Trp(12), Tyr(34))-bPTH(7-34), reportedly produces an anabolic bone response in vivo despite an activity profile that is dramatically different from that of other active ligands. This underscores a major challenge facing efforts to rationally design "biased" GPCR ligands for therapeutic application. While it is clearly plausible to identify functionally selective ligands, the ability to predict how bias will affect drug response in vivo, is often lacking, especially in complex disorders. PMID:23374189

Appleton, Kathryn M; Lee, Mi-Hye; Alele, Christian; Alele, Christine; Luttrell, Deirdre K; Peterson, Yuri K; Morinelli, Thomas A; Luttrell, Louis M



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: [Department of Medicine, University of California, Los Angeles (United States)] [Department of Medicine, University of California, Los Angeles (United States)



An acute intake of phosphate increases parathyroid hormone secretion and inhibits bone formation in young women.  


We studied the effects of a single oral phosphate (Pi) dose as well as those of three consecutive oral phosphate doses on calcium and bone metabolism. In the first part of the study (P1 study) 10 female volunteers were given orally 1500 mg of Pi in water, as a single dose, or plain water in randomized order at two different sessions. In the second part of the study (P3 study), 10 female volunteers were given orally 1500 mg of Pi, as three separate 500 mg doses in water, or plain water in randomized order. Calcium and bone metabolism was monitored for 24 h by measuring the concentrations of serum ionized calcium (S-iCa), urinary calcium, serum phosphate (S-P), urinary P, serum intact parathyroid hormone (PTH), serum carboxy-terminal propeptide of type I collagen (PICP), serum osteocalcin (BGP), serum carboxy-terminal telopeptide of type I collagen (ICTP), urine deoxypyridinoline (DPD) and bone-specific alkaline phosphatase activity (B-ALP). The S-P increased (p = 0.00005 and p = 0.0005, in the P1 and P3 studies, respectively), the S-iCa concentration declined significantly only in the P1 study (p = 0.0014), the urinary calcium excretion decreased (p = 0.02 and 0.013, in the P1 and P3 studies, respectively), and the PTH concentration rose (p = 0.0083 and p = 0.014, in the P1 and P3 studies, respectively) during the phosphate experiment as compared with the control session. Of the three markers of bone formation studied, PICP declined in the P1 study (p = 0.04), and B-ALP declined in both parts of the study (p = 0.027, p = 0.026, in the P1 and P3 studies, respectively) after phosphate administration, whereas there was no significant change in BGP in either of the studies. The markers of bone resorption, ICTP and DPD, were unaffected by the phosphate load in both studies. In conclusion, acute ingestion of phosphate leads to an increase in S-P, a decrease in S-iCa, and an increase in intact PTH secretion. Our results indicate that these events may lead to an acute inactivation of the early phases of bone formation. In this setting, there was no indication of enhanced bone resorption despite the increase in PTH secretion, which could be due to the combined effect of phosphate and PTH on bone resorption. PMID:8970892

Kärkkäinen, M; Lamberg-Allardt, C



Demographic, dietary, and serum factors and parathyroid hormone in the National Health and Nutrition Examination Survey  

PubMed Central

Summary Many determinants of parathyroid hormone (PTH) are unknown. In the National Health and Nutrition Examination Survey (NHANES), numerous factors not classically associated with calcium–phosphorus homeostasis, such as uric acid and smoking, are independently associated with PTH in adults without chronic kidney disease. Associations between serum phosphorus and PTH may vary by race. Introduction Although PTH may be an important biomarker for osteoporosis and cardiovascular disease, many determinants of PTH are unknown. We investigated associations between demographic, dietary, and serum factors and PTH level. Methods We studied 4,026 white, 1,792 black, and 1,834 Mexican-American adult participants without chronic kidney disease from the 2003–2004 and 2005–2006 NHANES. Results The mean serum PTH level was 38.3 pg/ml for whites, 42.6 pg/ml for blacks, and 41.3 pg/ml for Mexican-Americans. After adjusting for diet, body mass index, serum levels of calcium, phosphorus, 25-hydroxyvitamin D, creatinine, and other factors, smokers compared to non-smokers had lower PTH, ranging from ?4.2 pg/ml (95% confidence interval (CI) ?7.3 to ?1.1) in Mexican-Americans to ?6.1 pg/ml (95% CI ?8.7 to ?3.5) in blacks. After multivariate adjustment, PTH was higher in females compared to males, ranging from 1.1 pg/ml (95% CI ?1.2 to 3.4) in Mexican-Americans to 4.5 pg/ml (95% CI 1.9 to 7.0) in blacks, and in older (>60 years) compared to younger participants (<30 years), ranging from 3.7 pg/ml (95% CI 1.3 to 6.1) in Mexican-Americans to 8.0 pg/ml (95% CI 5.4 to 10.7) in blacks. Higher uric acid was associated with higher PTH. In whites only, lower serum phosphorus and lower serum retinol were associated with higher PTH. Conclusions Numerous factors not classically associated with calcium–phosphorus homeostasis are independently associated with PTH and should be considered in future studies of PTH and chronic disease. Additional research is needed to elucidate mechanisms underlying identified associations with PTH and to explore possible racial differences in phosphorus handling.

Farwell, W. R.; Taylor, E. N.



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

Microsoft Academic Search

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

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



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

Microsoft Academic Search

Summary  Several calcium supplements are currently available and many of them are marketed without proper comparison of the bioavailability of the actual preparations. The aim of the present trial was to evaluate and compare the acute changes in serum calcium (Ca) and parathyroid hormone (PTH) levels following the oral administration of a vehicle and of five calcium salts currently prescribed in

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



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



The Relationship Between Technetium-99m-Methoxyisobutyl Isonitrile Parathyroid Scintigraphy and Hormonal and Biochemical Markers in Suspicion of Primary Hyperparathyroidism  

PubMed Central

Objective: Technetium-99m-methoxyisobutyl isonitrile (Tc-99m MIBI) has been widely used to evaluate hyperfunctioning autonomous parathyroid glands in patients with elevated intact parathyroid hormone (iPTH) and/or calcium (Ca) level. The aim of this study was to evaluate the relationship between Tc-99m MIBI parathyroid scintigraphy and hormonal and biochemical markers in suspicion of primary hyperparathyroidism (PHPT). Material and Methods: Dual-phase Tc-99m MIBI parathyroid scintigraphy and total serum iPTH, Ca, phosphorus (P) and albumin measurements were performed in 60 patients (52 females, 8 males; mean age, 59.38±12.51 years; range, 34 to 86 years) with suspicion of PHPT. Results: The iPTH median level was 160.3 pg/mL (47.8 to 782.6). Thirty-five of the patients had surgical resection of hyperfunctioning parathyroid glands. Of the 35 patients, parathyroid gland pathology was detected in 30 patients using scintigraphic examination. Tc-99m MIBI parathyroid scintigraphy was negative in 30 patients. The iPTH, Ca and P levels were significantly different between in the Tc-99m MIBI positive group and the negative group, respectively: For iPTH, 202.1 (47.8-782.6) pg/mL versus 111.6 (80.1-373) pg/mL; p<0.001. For Ca, 11.7±1.15 mg/dL versus 10.3±1.05 mg/dL; p<0.001 and for P levels, 2.46±0.62 mg/dL versus 3.40±0.70 mg/dL; p<0.001). There was no significant difference in serum albumin levels between the MIBI positive and MIBI negative groups (4.25±0.27 g/dL versus 4.25±0.41 g/dL; p>0.05). Tc-99m MIBI parathyroid scintigraphy showed good correlation with iPTH level and histopathological diagnosis. Sensitivity and specificity was found 83.3% and 76.7%, respectively at the level of iPTH>147.7pg/mL. Conclusion: Tc-99m MIBI parathyroid scintigraphy is most likely to produce identification and localization of a parathyroid adenoma when both iPTH and Ca are elevated as well as decreased P levels. Conflict of interest:None declared.

Silov, Guler; Ozdal, Aysegul; Erdogan, Zeynep; Turhal, Ozgul; Karaman, Hatice



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


Human parathyroid hormone-related protein (hPTHrP), identified in patients with paraneoplastic hypercalcemia and expressed by different cell types during development and adult life, plays important roles in many human neoplasms. Immunohistochemical and RT-PCR analyses of hPTHrP and human parathyroid hormone receptor type 1 (PTHR-1) in primary medulloblastoma confirmed their expression in both classic and desmoplastic variants at RNA and protein levels. To evaluate the functional role of hPTHrP, DAOY and D283 medulloblastoma and U87MG glioma cells, expressing high levels of hPTHrP and PTHR-1, were treated with anti-sense oligonucleotides for hPTHrP. Anti-sense treatment produced in all cell lines a decrease of cell proliferation and clonogenic activity and an increase of apoptosis, while addition of exogenous hPTHrP (1-37) prevented these effects. Anti-sense induced the increase of Caspase-3, Fas (CD95) mRNAs and Bax/Bcl-2 mRNA ratio after 12 h of cell treatment. Exogenous hPTHrP (1-37) increased intracellular Ca(2+) concentration in DAOY cells as revealed by FURA. Anti-sense treated cells showed a significant decrease of steady-state levels of intracellular Ca(2+), which was reverted by addition of exogenous hPTHrP (1-37). This study indicates that hPTHrP and PTHR-1 are expressed in medulloblastoma and could promote tumor growth, protecting cells from apoptosis. PMID:17372745

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



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


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



Cutting Edge: Parathyroid Hormone Facilitates Macrophage Efferocytosis in Bone Marrow via Proresolving Mediators Resolvin D1 and Resolvin D2.  


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



A rare complication of transitional cell carcinoma of the renal pelvis: parathyroid hormone-related peptide-induced hypercalcaemia.  


We describe a rare occurrence of parathyroid hormone-related peptide (PTHrp) associated hypercalcaemia with a recurrence of transitional cell carcinoma of the renal pelvis. Our patient presented with serum calcium of 3.9?mmol/L, PTH of 5?ng/L and a PTHrp of 9.8?pmol/L (<2?pmol/L). He had no evidence of metastatic disease. His hypercalcaemia responded to bisphosphonate therapy. He chose to be treated conservatively and died 5?weeks after presentation. This is the seventh such case described in the literature. PTHrp-induced hypercalcaemia is associated with a grave prognosis, with a mean survival of 65?days from presentation. PMID:24951595

O Sullivan, Eoin; Plant, William



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

SciTech Connect

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

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



High- and low-flux acetate-free biofiltration: experimental assessment of calcium mass balance and intact parathyroid hormone behaviour.  


We studied total calcium mass balance and plasma intact parathyroid hormone behaviour in 10 uraemic patients who underwent acetate-free biofiltration carried out in accordance with six different dialytic schedules, where either a polyacrylonitrile or a polysulphone membrane was used. Schedules 1 and 2 involved a reinfusion flow rate of 33.3 ml/min with a dialysate calcium concentration (DCa) of 1.75 and 2 mmol/l respectively; in schedule 3, 4, 5 and 6 reinfusion flow rate amounted to 50 ml/min and DCa was respectively of 1.75, 2, 2.25 and 2.5 mmol/l. Dehydration remained unchanged in all schedules: 700 g/h. Finally high- and low-flux acetate-free biofiltration are able to induce different Ca mass balance which may suit different therapeutic contexts. Ca mass balance was either positive or negative depending on reinfusion flow rate and DCa. With a reinfusion flow rate of 33.3 ml/min a DCa of at least 2 mmol/l was necessary to obtain a positive mass balance, while with a reinfusion flow rate of 50 ml/min DCa had to equal 2.25 mmol/l. In high-flux acetate-free biofiltration, the estimation of predialytic Ca2+ and DCa values, using a simple formula, allows prediction of the mass balance that will be attained. At the end of acetate-free biofiltration, intact parathyroid hormone always decreased when a polyacrylonitrile membrane was employed while it increased, in the presence of negative Ca mass balance with a polysulphone membrane. PMID:7816296

de Vincenzi, A; Bellazzi, R G; Santagostino, M; Gazo, A; Romanini, D; Nai, M; Maretti, L; Ornati, G; Bellazzi, R



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

PubMed Central

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.

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



EBP50 Inhibits the Anti-Mitogenic Action of the Parathyroid Hormone Type 1 Receptor in Vascular Smooth Muscle Cells  

PubMed Central

Parathyroid hormone-related protein (PTHrP) and the parathyroid hormone type 1 receptor (PTH1R) are important regulators of vascular remodeling. PTHrP expression is associated to increased proliferation of vascular smooth muscle cells (VSMC). In contrast, signaling via the PTH1R inhibits cell growth. The mechanisms regulating the dual effect of PTHrP and PTH1R on VSMC proliferation are only partially understood. In this study we examined the role of the adaptor protein ezrin-radixin-moesin-binding phosphoprotein (EBP50) on PTH1R expression, trafficking, signaling and control of A10 cells proliferation. In normal rat vascular tissues, EBP50 was restricted to the endothelium with little expression in VSMC. EBP50 expression significantly increased in VSMC following angioplasty in parallel with PTHrP. Interestingly, PTHrP was able to induce EBP50 expression. In the clonal rat aortic smooth muscle cell line A10, EBP50 increased the recruitment of PTH1R to the cells membrane and delayed its internalization in response to PTHrP(1-36). This effect required an intact C-terminal motif in the PTH1R. In naive A10 cells, PTHrP(1-36) stimulated cAMP production but not intracellular calcium release. In contrast, PTHrP(1-36) induced both cAMP and calcium signaling in A10 cells over-expressing EBP50. Finally, EBP50 attenuated the induction of p27 kip1 and the antiproliferative effect of PTHrP(1-36). In summary, this study demonstrates the dynamic expression of EBP50 in vessels following injury and the effects of EBP50 on PTH1R function in VSMC. These finding highlight one of the mechanisms leading to increased VSMC proliferation and have important implication in the understanding of the molecular events leading to restenosis.

Song, Gyun Jee; Barrick, Stacey; Leslie, Kristen L.; Sicari, Brian; Fiaschi-Taesch, Nathalie M.; Bisello, Alessandro



CYP2D6, GST-M1 and GST-T1 enzymes: expression in parathyroid gland and association with the parathyroid hormone concentration during early renal replacement therapy  

PubMed Central

Aims The purpose of this research was to characterize CYP2D6, GST-M1 and GST-T1 enzyme expression in human parathyroid tissue, and to determine whether or not there is any association between deficiencies in these enzymes and serum parathyroid hormone concentrations in patients with end-stage renal disease. Methods Surgical human parathyroid tissue was obtained and evaluated by immunohistochemistry for cellular localization of CYP2D6, GST-M1 and GST-T1 and colocalization of CYP2D6 with parathyroid hormone. Blood samples were collected from 328 Caucasian patients with end-stage renal disease for genetic testing of CYP2D6*3, *4, *5, *6, *7 and GST-M1*0 and GST-T1*0 alleles. Clinical chemistry data and serum intact parathyroid hormone (iPTH) concentrations were obtained from patient medical records. In 277 of the patients, the same laboratory performed all clinical tests. Results CYP2D6, GST-M1 and GST-T1 were present in human parathyroid tissue. CYP2D6 was colocalized with parathyroid hormone in parathyroid chief cells. Within the end-stage renal disease population, a nonfunctional CYP2D6 genotype was present in 18.2%[95% confidence interval (CI) 8.0, 28.4] of patients in the 1st iPTH concentration quintile (iPTH < 64 pg mL?1), in 0% (95% CI 0, 7.5) of those in the 2nd quintile, in 1.8% (95% CI 0, 9.3) of those in the 3rd quintile, in 9.1% (95% CI 1.5, 16.7) of those in the 4th quintile, and in 16.7% (95% CI 6.8, 26.5) of those in the 5th quintile (iPTH > 347 pg mL?1) (P = 0.001). Out of 12 CYP2D6-deficient females, seven were in the 1st iPTH concentration quintile and the remaining five were in the 5th quintile. Patients deficient in the GST-M1 and GST-T1 enzymes displayed a far more uniform frequency distribution relative to serum iPTH concentrations. Conclusions The presence of CYP2D6, GST-M1 and GST-T1 in parathyroid cells was observed. An association is reported between a lack of CYP2D6 and iPTH concentrations in newly diagnosed end-stage renal disease patients. Gender and concomitant deficiency in GST-M1 and/or GST-T1 appear to define this association further. It remains to be established whether these associations reflect a cause-effect relationship between deficient expression of metabolizing enzymes and severity of secondary manifestation of renal failure.

Yan, Feng-Xiang; Langub, M Chris; Ihnen, Mark A; Hornung, Carlton; Juronen, Erkki; Rayens, Mary K; Cai, Wei-Min; Wedlund, Peter J; Fanti, Paolo



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

PubMed Central

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

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



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

Microsoft Academic Search

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

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



An Extrarenal Role for Parathyroid Hormone in the Disposal of Acute Acid Loads in Rats and Dogs  

PubMed Central

Acid infusion studies were performed in nephrectomized rats and dogs with either intact parathyroid glands (intact) or after thyroparathyroidectomy (thyroparathyroidectomized [TPTX]) to determine the role of parathyroid hormone (PTH) in extrarenal disposal and buffering of acutely administered acid. 29 intact rats given 5 mM/kg HCl and 6 intact dogs given 7 mM/kg HCl developed severe metabolic acidosis but all survived. However, each of 12 TPTX rats and 4 TPTX dogs given the same acid loads died. Intact rats and dogs buffered 39 and 50% of administered acid extracellularly, respectively, whereas extracellular buffering of administered acid was 97 and 78% in TPTX rats and dogs, respectively. 17 TPTX rats and 6 TPTX dogs given synthetic PTH 2 h before acid infusion survived. The blood bicarbonate and extracellular buffering in these animals, measured 2 h after acid infusion, was similar to intact animals. Changes in liver, heart, and skeletal muscle pH determined from [14C]5,5-dimethyl-2,4 oxazolidinedione distribution seemed insufficient to account for the increased cell buffering of PTH-replaced animals. Indeed, muscle pH in TPTX dogs given PTH and acid was only 0.06 pH units lower than in control dogs given no acid, suggesting that another tissue, presumably bone, was the target for PTH-mediated increased cell buffering. This conclusion was supported by the observation that PTH did not alter the pH of intact rat diaphragms in vitro. These results indicate that PTH is necessary for the optimal buffering of large, acute acid loads presumably by increasing bone buffering.

Fraley, Donald S.; Adler, Sheldon



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

Microsoft Academic Search

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%

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



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

Microsoft Academic Search

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

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



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



Combined effects of recombinant human BMP7 (rhBMP7) and parathyroid hormone (1–34) in metaphyseal bone healing  

Microsoft Academic Search

Fracture healing involves multiple stages of repair and coordinated actions of multiple cell types. Consequently, it may be possible to enhance healing through treatment strategies that target more than one repair process or cell type. The goal of this study was to determine the combined effects of recombinant human bone morphogenetic protein 7 (rhBMP-7) and parathyroid hormone (PTH(1–34)) on metaphyseal

Elise F. Morgan; Zachary D. Mason; Gavin Bishop; A. David Davis; Nathan A. Wigner; Louis C. Gerstenfeld; Thomas A. Einhorn



Parathyroid Hormone, Prostaglandin E 2 , and 1,25-Dihydroxyvitamin D 3 Decrease the Level of Na + Ca 2+ Exchange Protein in Osteoblastic Cells  

Microsoft Academic Search

.   We previously described Na+-Ca2+ exchange in osteoblastic rat osteosarcoma cells (UMR-106) and demonstrated that Na+-dependent Ca2+ transport was inhibited by 24-hour treatment of cells with parathyroid hormone (PTH), prostaglandin E2 (PGE2), or 1,25(OH)2D3. To determine whether this inhibition of Na+-Ca2+ exchange is at the level of exchanger protein synthesis we have examined exchanger protein levels using immunoblot analysis.\\u000a UMR-106

N. S. Krieger



Immunohistochemical localization of parathyroid hormone-related protein (PTHrP) and serum PTHrP in normocalcemic patients with oral squamous cell carcinoma  

Microsoft Academic Search

Cancer cells produce parathyroid hormone-related protein (PTHrP) in the early phase of malignancy development, before hypercalcemia occurs. The relationship between PTHrP and the clinicopathologic features of oral squamous cell carcinoma is poorly understood. We studied 60 patients (43 men, 17 women; mean age, 64.8 ± 11.2 years) with primary oral squamous cell carcinoma, from whom pretreatment biopsy specimens were obtained.

Makoto Tsuchimochi; Ayako Kameta; Mikiko Sue; Masataka Katagiri



Parathyroid Hormone-Related Protein Is an Essential Growth Factor for Human Clear Cell Renal Carcinoma and a Target for the von Hippel-Lindau Tumor Suppressor Gene  

Microsoft Academic Search

Clear cell renal carcinoma (CCRC) is responsible for 2% of cancer- related deaths worldwide and is resistant to virtually all therapies, indicating the importance of a search for new therapeutic targets. Parathyroid hormone-related protein (PTHrP) is a polyprotein derived from normal and malignant cells that regulates cell growth. In the current study, we show that blocking PTHrP with antibodies or

Thierry Massfelder; Herve Lang; Eric Schordan; Veronique Lindner; Sylvie Rothhut; Sandra Welsch; Patricia Simon-Assmann; Mariette Barthelmebs; Didier Jacqmin; Jean-Jacques Helwig


Localization of Parathyroid Hormone-related Protein in Breast Cancer Métastases: Increased Incidence in Bone Compared with Other Sites  

Microsoft Academic Search

Parathyroid hormone-related protein (FI'HrP) has recently been iden tified in 60% of a series of primary breast cancers. The detection of a bone-resorbing factor in tumors with a propensity to metastasize to bone prompted study of PTHrP in breast cancer metastasis. PTHrP »as localized by immunohistology in 12 of 13 (92%) breast cancer métastases in bone and in 3 of

Gerard J. Powell; Justine Southby; Janine A. Danks; Ross G. Stillwell; John A. Hayman; Michael A. Henderson; Richard C. Bennett; T. John Martin


Enhancement of recombinant human bone morphogenetic protein-2 (rhBMP-2)-induced new bone formation by concurrent treatment with parathyroid hormone and a phosphodiesterase inhibitor, pentoxifylline  

Microsoft Academic Search

We investigated the enhancement of new bone |formation elicited ectopically by recombinant human bone morphogenetic protein-2 (rhBMP-2), using parathyroid hormone (PTH) and a phosphodiesterase inhibitor (PDEi), pentoxifylline (PTX), in an animal model. Collagen sponge sheet discs containing rhBMP were implanted onto the back muscles of mice. PTX alone (200?mg\\/kg body weight [BW]), PTH(1–34) (10?µg\\/kg BW), PTX plus PTH (200?mg\\/kg BW

Hiroshi Horiuchi; Naoto Saito; Tetsuya Kinoshita; Shinji Wakabayashi; Takahiro Tsutsumimoto; Satoru Otsuru; Kunio Takaoka



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



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

Microsoft Academic Search

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

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



The release of parathyroid hormone and the exocytosis of a proteoglycan are modulated by extracellular Ca2+ in a similar manner.  

PubMed Central

Secretion of parathyroid hormone (PTH) is regulated in part by a classical "stimulus-secretion" pathway responsive to catecholamines. The primary physiological modulator of PTH exocytosis in parathyroid cells, however, is extracellular free Ca2+. Ca(2+)-modulated PTH release exhibits several characteristics suggestive of constitutive secretion. The aim of this work was to obtain further information about the possible intracellular origins of Ca(2+)-modulated exocytosis in parathyroid cells. Freshly dissociated bovine parathyroid cells labeled with [35S]sulfate synthesized a soluble chondroitin/dermatan sulfate proteoglycan (M(r) approximately 90-150 K) that was secreted into the medium. The export of [35S]sulfated proteoglycan satisfied several criteria that generally define constitutive release: 1) export is detected in the medium shortly (7-15 min) after a 5-min pulse, 2) there is minimal intracellular storage after equilibrium labeling (because of combined processes of rapid release and intracellular degradation), and 3) there is insensitivity to stimulation with isoproterenol, a known secretagogue in parathyroid cells. Nevertheless, the increase in extracellular Ca2+ from 0.5 to 2.0 mM reduced the export of the [35S]sulfated proteoglycan from 60% of total labeled to 30%. In addition, a secreted pool of immunoreactive PTH and [35S]sulfated proteoglycan was modulated by external Ca2+ to the same degree and sensitivity, although isoproterenol was more effective in stimulating the release of PTH than that of proteoglycan. Together, our experimental results show that in the parathyroid cell extracellular Ca2+ modulates negatively the export of both PTH and proteoglycan, a putative marker for constitutive secretion. We further suggest that a portion of newly synthesized PTH also enters this pathway, whereas another portion proceeds to an isoproterenol-releasable compartment from which the proteoglycan is largely excluded. Images

Muresan, Z; MacGregor, R R



A rare case of double parathyroid lipoadenoma with hyperparathyroidism.  


A rare case of double lipoadenomas of parathyroid glands with hyperparathyroidism is described. A 56-year-old woman was referred for management of diabetes. Work up revealed: serum Calcium (Ca) =11.9 mg/dl, glomerular filtration rate (GFR) = 103 ml/min/m2, parathyroid hormone (PTH) = 60 pg/ml, Phosphorus = 3.0 mg/dl, 25 hydroxy vitamin D (25 OH D) =16.5 ng/ml, 24 h urine Calcium =179 mg/day. Parathyroid sestamibi scan showed increased activity in the left thyroid and right thyroid lobe. Single photon emission computed tomography demonstrated uptake in inferior left and right thyroid lobes. Her serum calcium following successful bilateral parathyroidectomy was 9.3 mg/dl. Pathology showed double parathyroid lipoadenomas. After surgery, her serum Calcium and PTH normalized to 9.8 mg/dl and 32 pg/ml respectively. Lipoadenoma has been described as a very rare lesion of the parathyroid gland and is most commonly non-functional. PubMed search failed to reveal any case of hyperparathyroidism due to double parathyroid lipoadenomas. PMID:24157966

Ogrin, Cristina



Epigenetic Methylation of Parathyroid CaR and VDR Promoters in Experimental Secondary Hyperparathyroidism  

PubMed Central

Secondary hyperparathyroidism (s-HPT) in uremia is characterized by decreased expression in the parathyroids of calcium sensing (CaR) and vitamin D receptors (VDR). Parathyroid hormone (PTH) is normalized despite low levels of CaR and VDR after experimental reversal of uremia. The expression of CaR in parathyroid cultures decreases rapidly. Methylation of promoter regions is often detected during epigenetic downregulation of gene expression. Therefore, using an experimental rat model, we examined changes in methylation levels of parathyroid CaR and VDR promoters in vivo and in vitro. Methods. Uremia was induced by 5/6 nephrectomy. Melting temperature profiling of CaR and VDR PCR products after bisulfite treatment of genomic DNA from rat parathyroids was performed. Real-time PCR measured expression of PTH, CaR, VDR, and klotho genes in vitro. Results. Parathyroids from uremic rats had similar low levels of methylation in vivo and in vitro. In culture, a significant downregulation of CaR, VDR, and klotho within two hours of incubation was observed, while housekeeping genes remained stable for 24 hours. Conclusion. In uremic s-HPT and in vitro, no overall changes in methylation levels in the promoter regions of parathyroid CaR and VDR genes were found. Thus, epigenetic methylation of these promoters does not explain decreased parathyroid expression of CaR and VDR genes in uremic s-HPT.

Hofman-Bang, Jacob; Gravesen, Eva; Olgaard, Klaus; Lewin, Ewa



Amelioration of Type I Diabetes-induced Osteoporosis by Parathyroid Hormone is Associated with Improved Osteoblast Survival  

PubMed Central

Type 1 diabetic osteoporosis results from impaired osteoblast activity and death. Therefore, anti-resorptive treatments may not effectively treat bone loss in this patient population. Intermittent parathyroid hormone (PTH) treatment stimulates bone remodeling and increases bone density in healthy subjects. However, PTH effects may be limited in patients with diseases that interfere with its signaling. Here, we examined the ability of 8 and 40 ?g/kg intermittent PTH to counteract diabetic bone loss. PTH treatment reduced fat pad mass and blood glucose levels in non-diabetic PTH treated mice, consistent with PTH affecting glucose homeostasis. However, PTH treatment did not significantly affect general body parameters, including the blood glucose levels, of type 1 diabetic mice. We found that the high dose of PTH significantly increased tibial trabecular bone density parameters in control and diabetic mice, and the lower dose elevated trabecular bone parameters in diabetic mice. The increased bone density was due to increased mineral apposition and osteoblast surface, all of which are defective in type 1 diabetes. PTH treatment suppressed osteoblast apoptosis in diabetic bone, which could further contribute to the bone-enhancing effects. In addition, PTH treatment (40 ?g/kg) reversed preexisting bone loss from diabetes. We conclude that intermittent PTH may increase type 1 diabetic trabecular bone volume through its anabolic effects on osteoblasts.

Motyl, Katherine J.; McCauley, Laurie K.; McCabe, Laura R.



Calcium Dependent Ligand Binding and G-protein Signaling of Family B GPCR Parathyroid Hormone 1 Receptor Purified in Nanodiscs  

PubMed Central

GPCRs mediate intracellular signaling upon external stimuli, making them ideal drug targets. However, little is known about their activation mechanisms due to the difficulty in purification. Here, we introduce a method to purify GPCRs in nanodiscs, which incorporates GPCRs into lipid bilayers immediately after membrane solubilization, followed by single-step purification. Using this approach, we purified a family B GPCR, parathyroid hormone 1 receptor (PTH1R), which regulates calcium and phosphate homeostasis and is a drug target for osteoporosis. We demonstrated that the purified PTH1R in nanodiscs can bind to PTH(1-34) and activate G protein. We also observed that Ca2+ is a weak agonist of PTH1R and Ca2+ in millimolar concentration can switch PTH(1-34) from an inverse agonist to an agonist. Hence, our results show that nanodiscs are a viable vehicle for GPCR purification, enabling studies of GPCRs under precise experimental conditions without interference from other cellular or membrane components.

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



Nucleolar localization of parathyroid hormone-related peptide enhances survival of chondrocytes under conditions that promote apoptotic cell death.  

PubMed Central

Parathyroid hormone-related peptide (PTHrP) is a mediator of cellular growth and differentiation as well as a cause of malignancy-induced hypercalcemia. Most of the actions of PTHrP have been attributed to its interaction with a specific cell surface receptor that binds the N-terminal domain of the protein. Here we present evidence that PTHrP promotes some of its cellular effects by translocating to the nucleolus. Localization of transiently expressed PTHrP to the nucleolus was dependent on the presence of a highly basic region at the carboxyl terminus of the molecule that bears homology to nucleolar targeting sequences identified within human retroviral (human immunodeficiency virus type 1 and human T-cell leukemia virus type 1) regulatory proteins. Endogenous PTHrP also localized to the nucleolus in osseous cells in vitro and in vivo. Moreover, expression of PTHrP in chondrocytic cells (CFK2) delayed apoptosis induced by serum deprivation, and this effect depended on the presence of an intact nucleolar targeting signal. The present findings demonstrate a unique intracellular mode of PTHrP action and a novel mechanism by which this peptide growth factor may modulate programmed cell death.

Henderson, J E; Amizuka, N; Warshawsky, H; Biasotto, D; Lanske, B M; Goltzman, D; Karaplis, A C



Discovery of a Potent and Short-Acting Oral Calcilytic with a Pulsatile Secretion of Parathyroid Hormone  

PubMed Central

Short-acting oral calcilytics, calcium-sensing receptor (CaSR) antagonists, have been considered as alternatives for parathyroid hormone (PTH), an injectable bone anabolic drug used in the treatment of osteoporosis. Previously, we identified aminopropandiol 1, which transiently stimulated endogenous PTH secretion in rats. However, the inhibition of cytochrome P450 (CYP) 2D6 and the low bioavailability of 1 remain to be solved. Attempts to change the physicochemical properties of the highly lipophilic amine 1 by introduction of a carboxylic acid group as well as further structural modifications led to the discovery of the highly potent biphenylcarboxylic acid 15, with a markedly reduced CYP2D6 inhibition and a significantly improved bioavailability. Compound 15 evoked a rapid and transient elevation of endogenous PTH levels in rats after oral administration in a dose-dependent manner at a dose as low as 1 mg/kg. The PTH secretion pattern correlated with the pharmacokinetic profile and agreed well with that of the exogenous PTH injection which exerts a bone anabolic effect.



Parathyroid hormone-related peptide regulation of chick tibial growth plate chondrocyte maturation requires protein kinase A.  


Regulation of phenotype in chick tibial growth plate chondrocytes (GPCs) by parathyroid hormone-related peptide (PTHrP) is facilitated via signaling through three pathways: protein kinase A (PKA), protein kinase C (PKC) and inositol-1,4,5-trisphosphate-induced Ca2+ transients. To establish the underlying signaling specificity for PTHrP-regulation of chondrocyte maturation, we examined the separate involvement of each of these three pathways in the PTHrP regulation of key hallmarks of GPC phenotype: stimulation of proliferation and proteoglycan synthesis and reduction of alkaline phosphatase activity and type X collagen expression. Mimicking the PTHrP stimulation either of PKC with 1-oleoyl 2-acetyl glycerol or of a Ca2+ pulse with 65 mM KCl did not lead to PTHrP-like effects on any of the four markers examined. Also, inhibition of PKC with myr-psiPKC or blockade of Ca2+ signals with an intracellular chelator did not inhibit PTHrP action. However, PKA activation with dibutyryl cAMP mimicked PTHrP and blockade of PTHrP stimulation of PKA with H-89 inhibited the regulatory action of the factor. These data demonstrate that although activation of PKC or Ca2+ signals is not required, the cylic AMP-dependent A kinase is required for PTHrP to regulate key hallmarks of GPC phenotype. PMID:12382976

Zuscik, Michael J; O'Keefe, Regis J; Gunter, Thomas E; Puzas, J Edward; Schwarz, Edward M; Rosier, Randy N



Signaling by N- and C-terminal sequences of parathyroid hormone-related protein in hippocampal neurons.  

PubMed Central

Parathyroid hormone-related protein (PTHrP) is synthesized in the brain, and a single type of cloned receptor for the N-terminal portion of PTHrP and PTH is present in the central nervous system. Nothing is known about the physiological actions or signaling pathways used by PTHrP in the brain. Using cultured rat hippocampal neurons, we demonstrate that N-terminal PTHrP[1-34] and PTH[1-34] signal via cAMP and cytosolic calcium transients. The cAMP response showed strong acute (< or = 6 h) homologous and heterologous desensitization after preincubation with PTHrP or PTH. In contrast, the acute calcium response did not desensitize after preincubation with PTHrP; in fact, preincubation dramatically recruited additional responsive neurons. Unexpectedly, C-terminal PTHrP[107-139], which does not bind or activate the cloned PTH/PTHrP receptor, signaled in neurons via cytosolic calcium but not cAMP. Although some neurons responded to both PTHrP[1-34] and PTHrP[107-139], others responded only to PTHrP[1-34]. We conclude that certain hippocampal neurons exhibit dual signaling in response to PTHrP[1-34] and that some neurons have a receptor for C-terminal PTHrP that signals only via cytosolic calcium. Images Fig. 3 Fig. 4 Fig. 5 Fig. 7

Fukayama, S; Tashjian, A H; Davis, J N; Chisholm, J C



Regulation of parathyroid hormone release and cytosolic calcium by extracellular calcium in dispersed and cultured bovine and pathological human parathyroid cells.  

PubMed Central

Alterations in parathyroid glandular sensitivity to calcium may contribute to the hypersecretion of PTH in hyperparathyroidism. Since the cytosolic calcium concentration may mediate the effects of extracellular calcium on PTH release, we have employed the calcium-sensitive intracellular dye QUIN-2 to examine the relationship between extracellular calcium, cytosolic calcium, and PTH secretion in adult, neonatal, and cultured bovine as well as pathological human parathyroid cells. PTH release was measured using C- and N-terminal radioimmunoassays. Neonatal bovine parathyroid cells showed a greater set-point for secretion (the Ca++ concentration causing half of the maximal inhibition of PTH release) than adult cells (1.27 +/- 0.11 vs. 1.06 +/- 0.11 mM extracellular calcium, P less than 0.01), and a slightly higher extracellular calcium was necessary to raise the cytosolic calcium concentration to a given level in neonatal than in adult bovine parathyroid cells. In individual neonatal and adult cell preparations, there was a close correlation between the set-point for secretion and the "set-point" for cytosolic calcium (r = 0.832, P less than 0.001). In cells from five human parathyroid adenomas, which had an increase in set-point for secretion, the extracellular calcium concentration necessary to raise the cytosolic calcium concentration to a given level was slightly greater than in the neonatal cells. In four preparations of human parathyroid cells there was a significant correlation between the set-points for secretion and cytosolic calcium (r = 0.856, P less than 0.01). Because neonatal bovine and pathological human parathyroid glands show cellular hyperplasia, we studied the temporal relationship between cellular proliferation and the regulation of PTH release and cytosolic calcium concentration in cultured bovine parathyroid cells. Cellular proliferation, estimated by 3H-thymidine incorporation, increased significantly in culture from 104 +/- 10.1 counts/well on day 1 (first 24 h in culture) to 588 +/- 188 and 6,156 +/- 649 counts/well on days 2 and 4, respectively. In cultured cells on day 1, highly Ca++ (2-3 mM) inhibited maximal PTH release by 58.8 +/- 3.2%, which decreased significantly (P less than 0.001) to 38.2 +/- 1.9 and 17.1 +/- 3.7% on days 2 and 4, respectively. The cytosolic calcium observed at 3 mM calcium on day 1 was 701 +/- 43 nM, which declined to 466 +/- 60 and 314 +/- 14 nM on days 2 and 4 (P less than 0.05). There was a close correlation between this progressive decrease in maximal inhibition of PTH release and the cytosolic calcium at high extracellular calcium in cultured cells (r = 0.99, P < 0.001). Thus, during active proliferation of cultured cells, there is an alteration in the regulation of cytosolic calcium at a given extracellular calcium concentration, and changes in the regulation of PTH release and cytosolic calcium by extracellular calcium may be related to enhanced cellular proliferation.

LeBoff, M S; Shoback, D; Brown, E M; Thatcher, J; Leombruno, R; Beaudoin, D; Henry, M; Wilson, R; Pallotta, J; Marynick, S



Mitochondrial Membrane Potential Changes in Osteoblasts Treated with Parathyroid Hormone and Estradiol  

Microsoft Academic Search

This study assessed mitochondrial membrane potential changes in cultured osteoblasts treated with hormones known to regulate osteoblasts. A fluorescent carbocyanine dye, 5,5?, 6,6?-tetrachloro-1,1?, 3,3?-tetraethylbenzimidazolocarbocyanine iodide, also called JC-1, was used as a probe. JC-1 emits photons at 585 nm (orange–red) when the membrane potential in mitochondria is highly negative, but when the potential becomes reduced emission occurs at 527 nm

Michael B. Troyan; Virginia R. Gilman; Carol V. Gay



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.

Karaca, Halit



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


Parathyroid hormone increases circulating levels of fibronectin in vivo: modulating effect of ovariectomy.  


To explore the effect of PTH on circulating levels of fibronectin (FN), adult female Sprague-Dawley rats were implanted with Alzet minipumps prepared to deliver 7 pmol/h x kg BW of either human PTH (1-34) or human PTH (1-84). Both forms of the hormone led to significant and progressive increases in circulating levels of FN over the 72-h study period (P < 0.001). However, at every time point, circulating levels of FN with human PTH (hPTH) (1-84) infusion were significantly higher than with hPTH (1-34), such that at the end of the infusion, mean levels in the hPTH (1-34) group were 32.2 +/- 1.4 ng/ml, in the hPTH (1-84) group 93.8 +/- 5.4 ng/ml, and in the vehicle infused group 14.6 +/- 0.7 ng/ml. The greater agonist efficacy of hPTH (1-84) was not explained by differences in circulating levels of the hormones, and both forms of the hormone were equipotent at stimulating cAMP production by ROS 17/2.8 cells. However, hPTH (1-84) remained a more effective agonist than hPTH (1-34) at stimulating FN production in these cells (P < 0.001). Nephrectomy did not blunt the ability of PTH to increase circulating FN in vivo, indicating that the kidney was not the source of the FN produced in response to PTH. Pretreament with the potent bisphosphonate APD to block bone resorption also did not blunt the in vivo response to PTH. Parathyroidectomy did not blunt the response. Cultured fetal rat bones showed a significant 2.4-fold increase in FN production when treated with PTH. Consistent with our earlier in vitro studies (Endocrinology, 135: 1639-1644, 1994), estrogen deficiency, induced by ovariectomy, significantly diminished the ability of PTH to increase circulating FN levels in vivo (P < 0.001). We conclude that PTH increases circulating levels of FN in vivo and may be a physiologic regulator for the plasma form of this glycoprotein. The effects of PTH on circulating FN may reflect the anabolic properties of the hormone in bone and the blunted response following estrogen withdrawal could be a manifestation of the diminished bone formation vis-à-vis resorption seen in the estrogen deficient state. PMID:9275082

Sun, B H; Mitnick, M; Eielson, C; Yao, G Q; Paliwal, I; Insogna, K



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.

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



Mobilization of endogenous bone marrow derived endothelial progenitor cells and therapeutic potential of parathyroid hormone after ischemic stroke in mice.  


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

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



Endotoxin increases parathyroid hormone-related protein mRNA levels in mouse spleen. Mediation by tumor necrosis factor.  

PubMed Central

Parathyroid hormone-related protein (PTHrP) causes hypercalcemia in malignancy. However, the role and regulation of PTHrP in normal physiology is just beginning to be explored. PTHrP is found in the spleen and has several other features common to cytokines. Since endotoxin (LPS) causes many of its effects indirectly by inducing cytokines, studies were undertaken to determine whether LPS might also induce splenic PTHrP expression. LPS (100 ng/mouse) increased splenic PTHrP mRNA levels 3.6-fold in C3H/OuJ mice. This effect was maximal at 2 h and returned to baseline by 4 h. PTHrP peptide levels also increased 3.3-fold in splenic extracts in response to LPS (1 microgram/mouse). Murine TNF-alpha and human IL-1 beta, cytokines that mediate many of the effects of LPS, also increased splenic PTHrP mRNA levels. LPS-resistant C3H/HeJ mice, which produce minimal amounts of TNF and IL-1 in response to LPS, were resistant to LPS induction of splenic PTHrP mRNA, while TNF-alpha and IL-1 beta readily increased PTHrP mRNA levels in C3H/HeJ mice. Anti-TNF antibody blocked LPS induction of splenic PTHrP mRNA in C3H/OuJ mice by 68%, indicating that TNF is a mediator of the LPS induction of PTHrP levels. In contrast, an IL-1 receptor antagonist (IL-1ra) was ineffective. The increase in PTHrP in the spleen during the immune response suggests that PTHrP may play an important role in immune modulation, perhaps by mediating changes in lymphocyte proliferation and/or function. Images

Funk, J L; Krul, E J; Moser, A H; Shigenaga, J K; Strewler, G J; Grunfeld, C; Feingold, K R



Activation of Vascular Smooth Muscle Parathyroid Hormone Receptor Inhibits Wnt/?-Catenin Signaling and Aortic Fibrosis in Diabetic Arteriosclerosis  

PubMed Central

Rationale Vascular fibrosis and calcification contribute to diabetic arteriosclerosis, impairing Windkessel physiology necessary for distal tissue perfusion. Wnt family members up-regulated in arteries by the low-grade inflammation of “diabesity” -- stimulate type I collagen expression and osteogenic mineralization of mesenchymal progenitors via ?-catenin. Conversely, parathyroid hormone (PTH) inhibits aortic calcification in LDLR (low density lipoprotein receptor)-deficient mice fed high fat diabetogenic diets (HFD). Objective We wished to determine the impact of vascular PTH receptor (PTH1R) activity on arteriosclerotic Wnt/?-catenin signaling in vitro and in vivo. We generated SM-caPTH1R transgenic mice, a model in which the constitutively active PTH1R variant H223R (caPTH1R) is expressed only in the vasculature. Methods and Results The caPTH1R inhibited Wnt/?-catenin signaling, collagen production, and vascular smooth muscle cell (VSMC) proliferation and calcification in vitro. Transgenic SM-caPTH1R;LDLR+/? mice fed HFD develop “diabesity,” with no improvements in fasting serum glucose, cholesterol, weight, body composition, or bone mass vs. LDLR+/? siblings. SM-caPTH1R down-regulated aortic Col1A1, Runx2, and Nox1 expression without altering TNF, Msx2, Wnt7a/b, or Nox4. The SM-caPTH1R transgene decreased aortic ?-catenin protein accumulation and signaling in diabetic LDLR+/? mice. Levels of aortic superoxide -- a precursor of peroxide that activates pro-MMP9 and osteogenic signaling in VSMCs -- were suppressed by the SM-caPTH1R transgene. Aortic calcification, collagen accumulation, and wall thickness were concomitantly reduced, enhancing vessel distensibility. Conclusions Cell-autonomous VSMC PTH1R activity inhibits arteriosclerotic Wnt/?-catenin signaling and reduces vascular oxidative stress, thus limiting aortic type I collagen and calcium accrual in diabetic LDLR-deficient mice.

Cheng, Su-Li; Shao, Jian-Su; Halstead, Linda R.; Distelhorst, Kathryn; Sierra, Oscar; Towler, Dwight A.



Enhanced Bone Morphogenetic Protein-2-Induced Ectopic and Orthotopic Bone Formation by Intermittent Parathyroid Hormone (1-34) Administration  

PubMed Central

Bone morphogenetic proteins (BMPs) play a central role in local bone regeneration strategies, whereas the anabolic features of parathyroid hormone (PTH) are particularly appealing for the systemic treatment of generalized bone loss. The aim of the current study was to investigate whether local BMP-2-induced bone regeneration could be enhanced by systemic administration of PTH (1–34). Empty or BMP-2-loaded poly(lactic-co glycolic acid)/poly(propylene fumarate)/gelatin composites were implanted subcutaneously and in femoral defects in rats (n?=?9). For the orthotopic site, empty defects were also tested. Each of the conditions was investigated in combination with daily administered subcutaneous PTH (1–34) injections in the neck. After 8 weeks of implantation, bone mineral density (BMD) and bone volume were analyzed using microcomputed tomography and histology. Ectopic bone formation and almost complete healing of the femoral defect were only seen in rats that received BMP-2-loaded composites. Additional treatment of the rats with PTH (1–34) resulted in significantly (p?

Kempen, Diederik H.R.; Hefferan, Theresa E.; Creemers, Laura B.; Heijink, Andras; Maran, Avudaiappan; Dhert, Wouter J.A.; Yaszemski, Michael J.




PubMed Central

Summary Because of recent insights into the pathogenesis of age-related bone loss, we investigated whether intermittent parathyroid hormone (PTH) administration antagonizes the molecular mechanisms of the adverse effects of aging on bone. PTH produced a greater increase in vertebral trabecular bone mineral density and bone volume as well as a greater expansion of the endocortical bone surface in the femur of 26 as compared to 6 month old female C57BL/6 mice. Moreover, PTH increased trabecular connectivity in vertebrae and the toughness of both vertebrae and femora in old, but not young, mice. PTH also increased the rate of bone formation and reduced osteoblast apoptosis to a greater extent in the old mice. Most strikingly, PTH reduced reactive oxygen species (ROS), p66Shc phosphorylation and expression of the lipoxygenase Alox15; and it increased glutathione and stimulated Wnt signaling in bone of old mice. PTH also antagonized the effects of oxidative stress on p66Shc phosphorylation, FoxO transcriptional activity, osteoblast apoptosis, and Wnt signaling in vitro. In contrast, administration of the antioxidants N-acetyl cysteine or pegylated catalase reduced osteoblast progenitors, and attenuated proliferation and Wnt signaling. These results suggest that PTH has a greater bone anabolic efficacy in old age because in addition to its other positive actions on bone formation it antagonizes the age-associated increase in oxidative stress and its adverse effects on the birth and survival of osteoblasts. On the other hand, ordinary antioxidants cannot restore bone mass in old age because they slow remodeling and attenuate osteoblastogenesis by interfering with Wnt signaling.

Jilka, R.L.; Almeida, M.; Ambrogini, E.; Han, L.; Roberson, P. K.; Weinstein, R.S.; Manolagas, S.C.



Defective postnatal endochondral bone development by chondrocyte-specific targeted expression of parathyroid hormone type 2 receptor.  


The human parathyroid hormone type 2 receptor (PTH2R) is activated by PTH and by tuberoinfundibular peptide of 39 residues (TIP39), the latter likely acting as its natural ligand. Although the receptor is expressed at highest levels in the nervous system, we have observed that both PTH2R and TIP39 are expressed in the newborn mouse growth plate, with the receptor localizing in the resting zone and the ligand TIP39 localizing exclusively in prehypertrophic and hypertrophic chondrocytes. To address the role of PTH2R in postnatal skeletal growth and development, Col2a1-hPTH2R (PTH2R-Tg) transgenic mice were generated. The mice were viable and of nearly normal size at birth. Expression of the transgene in the growth plate was limited to chondrocytes. We found that chondrocyte proliferation was decreased, as determined by in vivo BrdU labeling of proliferating chondrocytes and CDK4 and p21 expression in the growth plate of Col2a1-hPTH2R transgenic mice. Similarly, the differentiation and maturation of chondrocytes was delayed, as characterized by decreased Sox9 expression and weaker immunostaining for the chondrocyte differentiation markers collagen type II and type X and proteoglycans. As well, there was altered expression of Gdf5, Wdr5, and ?-catenin, factors implicated in chondrocyte maturation, proliferation, and differentiation.These effects impacted on the process of endochondral ossification, resulting in delayed formation of the secondary ossification center, and diminished trabecular bone volume. The findings substantiate a role for PTH2R signaling in postnatal growth plate development and subsequent bone mass acquisition. PMID:23092913

Panda, Dibyendu Kumar; Goltzman, David; Karaplis, Andrew C



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.



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.



Serum Uric Acid Is Associated with Left Ventricular Hypertrophy Independent of Serum Parathyroid Hormone in Male Cardiac Patients  

PubMed Central

Background Several studies have shown that serum uric acid (UA) is associated with left ventricular (LV) hypertrophy. Serum levels of parathyroid hormone (PTH), which has bbe shown to be correlated with UA, is also known to be associated with cardiac hypertrophy; however, whether the association between UA and cardiac hypertrophy is independent of PTH remains unknown. Purpose We investigated whether the relationship between serum uric acid (UA) and LV hypertrophy is independent of intact PTH and other calcium-phosphate metabolism-related factors in cardiac patients. Methods and Results In a retrospective study, the association between UA and left ventricular mass index was assessed among 116 male cardiac patients (mean age 65±12 years) who were not taking UA lowering drugs. The median UA value was 5.9 mg/dL. Neither age nor body mass index differed significantly among the UA quartile groups. Patients with higher UA levels were more likely to be taking loop diuretics. UA showed a significant correlation with intact PTH (R?=?0.34, P<0.001) but not with other calcium-phosphate metabolism-related factors. Linear regression analysis showed that log-transformed UA showed a significant association with left ventricular mass index, and this relationship was found to be significant exclusively in patients who were not taking loop and/or thiazide diuretics. Multivariate logistic regression analysis showed that log-transformed UA was independently associated with LV hypertrophy with an odds ratio of 2.79 (95% confidence interval 1.48–5.28, P?=?0.002 per one standard deviation increase). Conclusions Among cardiac patients, serum UA was associated with LV hypertrophy, and this relationship was, at least in part, independent of intact PTH levels, which showed a significant correlation with UA in the same population.

Fujita, Shu-ichi; Okamoto, Yusuke; Shibata, Kensaku; Morita, Hideaki; Ito, Takahide; Sohmiya, Koichi; Hoshiga, Masaaki; Ishizaka, Nobukazu



Induction of parathyroid hormone-related peptide following peripheral nerve injury: role as a modulator of Schwann cell phenotype.  


Parathyroid hormone-related peptide (PTHrP) is widely distributed in the rat nervous system, including the peripheral nervous system, where its function is unknown. PTHrP mRNA expression has recently been shown to be significantly elevated following axotomy of sympathetic ganglia, although the role of PTHrP was not investigated. The role of PTHrP in peripheral nerve injury was investigated in this study using the sciatic nerve injury model and dorsal root ganglion (DRG) explant model of nerve regeneration. We find that PTHrP is a constitutively secreted peptide of proliferating Schwann cells and that the PTHrP receptor (PTH1R) mRNA is expressed in isolated DRG and in sciatic nerve. Using the sciatic nerve injury model, we show that PTHrP is significantly upregulated in DRG and in sciatic nerve. In addition, in situ hybridization revealed significant localization of PTHrP mRNA to Schwann cells in the injured sciatic nerve. We also find that PTHrP causes a dramatic increase in the number of Schwann cells that align with and bundle regrowing axons in explants, characteristic of immature, dedifferentiated Schwann cells. In addition to stimulating migration of Schwann cells along the axonal membrane, PTHrP also stimulates migration on a type 1 collagen matrix. Furthermore, treatment of purified Schwann cell cultures with PTHrP results in the rapid phosphorylation of the cAMP response element protein, CREB. We propose that PTHrP acts by promoting the dedifferentiation of Schwann cells, a critical requirement for successful nerve regeneration and an effect consistent with known PTHrP functions in other cellular differentiation programs. PMID:16470617

Macica, Carolyn M; Liang, Guoying; Lankford, Karen L; Broadus, Arthur E



Parathyroid Hormone Induction of Cyclooxygenase-2 in Murine Osteoblasts: Role of the Calcium-Calcineurin-NFAT Pathway  

PubMed Central

Murine MC3T3-E1 and MC-4 cells were stably transfected with ?371/+70 bp of the murine cyclooxygenase-2 (COX-2) promoter fused to a luciferase reporter (Pluc371) or with Pluc371 carrying site-directed mutations. Mutations were made in (1) the cAMP response element (CRE) at ?57/?52 bp, (2) the activating protein-1 (AP-1)–binding site at ?69/?63 bp, (3) the nuclear factor of activated T-cells (NFAT)–binding site at ?77/?73 bp, and (4) both the AP-1 and NFAT sites, which comprise a composite consensus sequence for NFAT/AP-1. Single mutation of CRE, AP-1, or NFAT sites decreased parathyroid hormone (PTH)–stimulated COX-2 promoter activity 40% to 60%, whereas joint mutation of NFAT and AP-1 abrogated the induction. On electrophoretic mobility shift analysis, PTH stimulated binding of phosphorylated CREB to an oligonucleotide spanning the CRE and binding of NFATc1, c-Fos, and c-Jun to an oligonucleotide spanning the NFAT/AP-1 composite site. Mutation of the NFAT site was less effective than mutation of the AP-1 site in competing binding to the composite element, suggesting that cooperative interactions of NFATc1 and AP-1 are more dependent on NFAT than on AP-1. Both PTH and forskolin, an activator of adenylyl cyclase, stimulated NFATc1 nuclear translocation. PTH- and forskolin-stimulated COX-2 promoter activity was inhibited 56% to 80% by calcium chelation or calcineurin inhibitors and 60% to 98% by protein kinase A (PKA) inhibitors. These results indicate an important role for the calcium-calcineurin-NFAT signaling pathway in the PTH induction of COX-2 and suggest that cross-talk between the cAMP/PKA pathway and the calcium-calcineurin-NFAT pathway may play a role in other functions of PTH in osteoblasts. © 2010 American Society for Bone and Mineral Research

Huang, Hechang; Chikazu, Daichi; Voznesensky, Olga S; Herschman, Harvey R; Kream, Barbara E; Drissi, Hicham; Pilbeam, Carol C



Parathyroid adenoma with coeliac disease: primary or quaternary hyperparathyroidism?  


Coeliac disease is a gluten-sensitive enteropathy of varying severity. Osteomalacia and hypocalcaemia can result from malabsorption of vitamin D and calcium, which, in turn, can lead to secondary hyperparathyroidism. If coeliac disease remains untreated for long, tertiary hyperparathyroidism can also develop through autonomy of the parathyroid glands via chronic stimulation. Primary hyperparathyroidism also has been reported in some cases of coeliac disease. We report the case of an adolescent with coeliac disease presenting with severe hypercalcaemia from a parathyroid adenoma. A 14 year-old girl was admitted to our department for delayed puberty and growth retardation. Laboratory examination revealed iron deficiency anaemia, low 25OH vitamin D level (7 ng/ml), high parathyroid hormone level (PTH) (955 pg/ml), and hypercalcaemia (13.4 mg/dl). Endoscopic biopsy was compatible with gluten enteropathy. Endomysium antibody was positive. A gluten-free diet was started. Her calcium returned to normal after excision of the parathyroid adenoma. After four months of the gluten-free diet, she began to mature, and puberty began with development of breasts and axillary-pubic hair growth. It has been suggested that autonomous four-gland hyperplasia or tertiary hyperparathyroidism may progress to adenoma formation, and that this should be termed "quaternary hyperparathyroidism". More studies are required to explain the relationship between coeliac disease and hyperparathyroidism. PMID:22378099

Anaforoglu, Inan; Ersoy, Kerem; Algun, Ekrem



[Preanalytical variability of parathyroid hormone measurement in dialysis patients; application to Elecsys 2010 (Roche) automate].  


The working group PTH-Vitamin D of the SFBC recently underlined the great intertechnic variability of parathormone (PTH) assays. At the same time, the data of the literature showed an impact of the preanalytic stage, significant and variable according to the automat used. We worked on the automat Roche Elecsys. On quickly centrifuged and decanted samples, the small difference in results between serum and plasma EDTA (6%) is compatible with an indifferent use of the two samples for dialysed patients. The reputation of greater stability on plasma EDTA seems primarily based on studies after decantation of plasma. The extension to a non decanted sample, maintained on primary tube for deferred shipping to the laboratory would require verification. Concerning the serum, on tube with serum separator, after early centrifugation, we checked the stability of the PTH measurement for a delay lower than or equal to 4 hours. For an extrahospital structure of dialysis, in the conditions of an early and an on site centrifugation, this delay allows to defer the transport of the primary closed tube to the laboratory. Contrary to plasma EDTA, the serum also allows simultaneous measurements of other parameters used for the care of the dialysed patients. PMID:18227004

Parent, X; Alenabi, F; Etienne, E; Brignon, P; Chantrel, F; Meynaud-Kraemer, L



Study on preparation and activity of a novel recombinant human parathyroid hormone(1-34) analog with N-terminal Pro-Pro extension.  


A recombinant human parathyroid hormone fragment, Pro-Pro-hPTH(1-34), with molecular weight of 4311.46 was acquired through gene engineering. It was then isolated and purified. The homogeneity of this fragment was characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), high performance liquid chromatography(HPLC), isoelectronic focusing (IEF) electrophoresis and mass spectrometry(MS) methods. Its isoelectric point is 8.0 which was determined by IEF. It was found that the hormone fragment significantly induced calcium increment as compared to the control group (P<0.001) in Parsons's Chicken Assay, an established bioassay for the evaluation of the PTH effect. After the 3-month-old ovariectomized (OVXed) rats, the OVXed rat is one of the two models required by the U.S. Food and Drug Administration for the preclinical assessment of drugs for treating osteoporosis [DeLuca PP, Dani BA. Skeletal effects of parathyroid hormone (1-34) in ovariectomized rats with or without concurrent administration of salmon calcitonin. Am Assoc Pharm Sci 2001;3(4):E27 [1

Chunxiao, Wang; Jingjing, Liu; Yire, Xiao; Min, Ding; Zhaohui, Wang; Gaofu, Qi; Xiangchun, Shen; Xuejun, Wang; Jie, Wu; Taiming, Li



Conjugated linoleic acid is related to bone mineral density but does not affect parathyroid hormone in men.  


The relationships between conjugated linoleic acid (CLA) status, bone, body composition, and the effect of CLA on calciotropic hormones are unclear. A cross-sectional study was designed to examine the association between c9, t11 CLA status in erythrocyte membranes (RBC) and body composition. This preceded a dose-response trial investigating if c9, t11 CLA affected parathyroid hormone (PTH). It was hypothesized that (1) higher c9, t11 CLA status in RBC will be associated with a lower fat and higher bone mass and that (2) PTH will be reduced by 30% after supplementation of c9, t11 CLA. Fifty-four men (age, 19-53 years) were included in the cross-sectional analysis, of which 31 were studied in the dose-response trial and randomized to 1 of 3 groups: placebo (n = 10), 1.5 g/d (n = 11), or 3.0 g/d (n = 10) of c9, t11 CLA for 16 weeks. Men with RBC c9, t11 CLA status above the median had higher whole body bone mineral density (BMD) (1.359 ± 0.024 vs 1.287 ± 0.023 g/cm(2); P = .04) and whole body lean mass (WBL) percentage (78.8% ± 0.9% vs 75.3% ± 1.0%; P = .01), whereas body mass index (24.8 ± 0.5 kg/m(2) vs 27.3 ± 0.9 kg/m(2); P = .01) and whole body fat mass percentage (17.3% ± 0.9% vs 21.3% ± 1.1%; P = .007) were lower. In regression analysis, RBC c9, t11 CLA status accounted for a significant proportion (r(2) = 0.10) of the variation in whole body BMD (P = .03). There were no time or treatment differences among any bone or biomarkers of bone metabolism including PTH. These findings indicate that RBC c9, t11 CLA status, a reflection of long-term (~4 months) dietary CLA intake, positively relates to BMD. However, c9, t11 CLA supplementation does not appear to affect PTH in healthy men. PMID:23244536

Deguire, Jason R; Makarem, Nour; Vanstone, Catherine A; Morin, Suzanne; Duque, Gustavo; Weiler, Hope A



Parathyroid gland function in secondary hyperparathyroidism  

Microsoft Academic Search

The parathyroid glands play a critical role in the maintenance of calcium homeostasis. It has been suggested that the set-point for calcium-regulated parathyroid hormone (PTH) release is higher in uremic patients than normal subjects. However, these assessments of parathyroid gland function have been performed using methods that differed from the original four-parameter model. Dynamic testing of the parathyroid glands has

Isidro B. Salusky; William G. Goodman



Effects of anti-parathyroid hormone-related protein monoclonal antibody and osteoprotegerin on PTHrP-producing tumor-induced cachexia in nude mice  

Microsoft Academic Search

We have previously demonstrated that parathyroid hormone-related protein (PTHrP) is a cachexia inducer, but it is still not\\u000a known what PTHrP effects on target tissues induce the cachexia. Therefore, we examined the effects of anti-PTHrP antibody\\u000a and osteoprotegerin (OPG) on PTHrP-producing tumor-induced cachexia. Nude mice bearing PTHrP-producing human lung cancer cells\\u000a (HARA-B) exhibited cachexia with hypercalcemia 3–4 weeks after inoculation,

Haruo Iguchi; Yuko Aramaki; Shigeaki Maruta; Soichi Takiguchi



Effects of parathyroid hormone alone or in combination with antiresorptive therapy on bone mineral density and fracture risk – a meta-analysis  

Microsoft Academic Search

Aim   The effects of parathyroid hormone (PTH) alone or in combination with antiresorptive therapy on changes in bone mineral density\\u000a (BMD) and fracture risk were studied.\\u000a \\u000a \\u000a \\u000a Materials and methods   Randomised placebo controlled trials were retrieved from the PubMed, Web of Science or Embase databases.\\u000a \\u000a \\u000a \\u000a Results   PTH alone or in combination with antiresorptive drugs reduced vertebral [relative risk (RR)=0.36, 95% confidence

P. Vestergaard; N. R. Jorgensen; L. Mosekilde; P. Schwarz



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


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

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



Na,K-ATPase activity and 25(OH)vitamin D 3 hydroxylation in rat proximal tubules  

Microsoft Academic Search

The proximal tubule is the target site for parathyroid hormone (PTH), and conversion of 25(OH)vitamin D3 hormones which impinge on calcium (Ca) homeostatis, as well as a major site for sodium (Na) reabsorption. The effect of changes in PTH and vitamin D status on Na,K-ATPase activity, as a measure of Na transport, were studied in the proximal tubules of adult

Deborah Elstein; Justin Silver



Differential effects of acute administration of 19Nor1,25-dihydroxy-vitamin D 2 and 1,25-dihydroxy-vitamin D 3 on serum calcium and phosphorus in hemodialysis patients  

Microsoft Academic Search

Background: Treatment of hyperparathyroidism includes the use of 1,25-dihydroxy-vitamin D3 (1,25D3) to suppress parathyroid hormone (PTH), but dosing of 1,25D3 is limited by the development of hypercalcemia and a high calcium × phosphorus (Ca × P) product because of gut absorption of calcium and phosphorus and enhanced bone resorption. The vitamin D analogue 19-nor-1,25(OH)2-vitamin D2 (19-Nor) causes less hypercalcemia and

Daniel W. Coyne; Marvin Grieff; Shubhada N. Ahya; Karla Giles; Kathy Norwood; Eduardo Slatopolsky



Parathyroid hormone-related protein: isolation, molecular cloning, and mechanism of action.  


Many factors, such as interleukin 1, TGF alpha, tumor necrosis factor alpha and beta, and PGs, have been implicated in etiological roles in HHM (Martin and Mundy, 1987). Much interest in the past has also centered upon the likelihood of ectopic secretion of PTH in this condition. We have purified a protein (PTHrP) implicated in HHM from a human lung cancer cell line (BEN). Full-length cDNA clones have been isolated and were found to encode a prepropeptide of 36 amino acids and a mature protein of 141 amino acids. Eight of the first 13 amino acids were identical with human PTH, although antisera directed to the NH2 terminus of PTHrP do not recognize PTH; this homology is not maintained in the remainder of the molecule. PTHrP therefore represents a previously unrecognized hormone, possibly related to the PTH gene by a gene duplication mechanism. In support of this notion, the PTHrP gene has been localized to the short arm of chromosome 12; it is believed that chromosome 11, containing the PTH gene, and chromosome 12 are evolutionarily related. In addition, the human PTHrP gene has been isolated, characterized, and shown to have a similar intron--exon organization as the PTH gene. It is possible that the original ancestral gene is indeed the PTHrP gene; resolution of this question awaits studies in lower species. Peptides synthesized to the predicted protein sequence have enabled detailed structure-function studies that have identified NH 2-terminal sequences to be responsible for the biological effects of the molecule. Antibodies raised against the various synthetic peptides have led to the immunohistochemical localization of PTHrP in many human squamous cell carcinomas as well as in a subpopulation of keratinocytes of normal skin. The availability of these antibodies has opened the way for the development of a radioimmunoassay to detect PTHrP in the sera of cancer patients at risk of developing hypercalcemia. The recent characterization of PTHrP-like activity in the ovine fetus suggests some physiological function for PTHrP. It is possible that PTHrP, as the fetal counterpart of PTH, has the role of maintaining the maternal-fetal calcium gradient. The isolation and characterization of PTHrP have added to our understanding of the mechanisms of hypercalcemia and may contribute to the understanding of other metabolic bone diseases, such as osteoporosis and Paget's disease. Finally, and perhaps most importantly, PTHrP may play a hitherto unrecognized role in normal cell physiology. PMID:2682846

Martin, T J; Allan, E H; Caple, I W; Care, A D; Danks, J A; Diefenbach-Jagger, H; Ebeling, P R; Gillespie, M T; Hammonds, G; Heath, J A



Expression of Parathyroid-Specific Genes in Vascular Endothelial Progenitors of Normal and Tumoral Parathyroid Glands  

PubMed Central

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

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



Parathyroid transplantation  

Microsoft Academic Search

This is a review of our current experience with the technique of parathyroid transplantation in man. We have performed 68 autografts and 2 allografts. The indications for parathyroid autotransplantation include primary and secondary parathyroid hyperplasia, repeat neck exploration for persistent or recurrent hyperparathyroidism, and total thyroidectomy for carcinoma. Indications for allotransplantation include the unsuccessful medical management of hypoparathyroidism and complete

Samuel A. Wells; Jerry A. Stirman; R. Morton Bolman



Effects of calcitriol on parathyroid function and on bone remodelling in secondary hyperparathyroidism  

Microsoft Academic Search

Background. Secondary hyperparathyroidism (2HPT) develops in chronic renal failure due to disturbances of calcium, phosphorus and vitamin D metabolism. It is characterized by high turnover bone disease and an altered calcium-parathyroid hormone (PTH) relation- ship. Calcitriol has been widely used for the treatment of 2HPT. However, it remains controversial whether calcitriol is capable of inducing changes of the calcium-PTH curve.

Melani Custodio Ribeiro; Rosa Maria Affonso Moyses; Vanda Jorgetti


Transcriptional activation of Gs alpha expression by retinoic acid and parathyroid hormone-related protein in F9 teratocarcinoma cells.  


Cyclic AMP is known to enhance retinoic acid-induced differentiation of F9 mouse teratocarcinoma cells to parietal endoderm. Recently, we showed that a parathyroid hormone-related protein (PTHrP), by activating adenylate cyclase, can substitute for exogenous cAMP in promoting retinoic acid-induced differentiation of F9 cells. However, the mechanisms by which endogenous cAMP levels are regulated during F9 differentiation are poorly defined. We therefore assessed whether Gs alpha, a subunit of the stimulatory coupling protein of adenylate cyclase, is induced during this process. Treatment of F9 cells with retinoic acid (1 microM) for 5 days resulted in a 20-fold increase in steady-state levels of a 2.0-kilobase Gs alpha mRNA. This was accompanied by an increase in the expression of 52- and 45-kDa Gs alpha polypeptides. Gs alpha mRNA increases within 24 h of exposure to retinoic acid, whereas the expression of alpha 1 (IV) collagen, a marker for F9 differentiation, did not increase until 48 h of treatment. In the presence of retinoic acid, exogenous human PTHrP-(1-34)-amide (20 nM) produced a further 2-fold increase in Gs alpha mRNA. These effects of retinoic acid and PTHrP were exerted largely if not entirely at the level of Gs alpha gene transcription, as assessed by nuclear run-on assay. Bt2cAMP (1 mM) did not reproduce the stimulatory effects of PTHrP on Gs alpha transcription, mRNA, or protein. These data demonstrate that a marked increase in Gs alpha expression accompanies F9 differentiation induced by retinoic acid and PTHrP, and that the regulation is predominantly transcriptional. The resulting increase in adenylate cyclase responsiveness to PTHrP and perhaps other ligands may be a critical component of the differentiation process. The effect of PTHrP on the expression of Gs alpha appears to be mediated by signals other than cAMP. PMID:2122968

Chan, S D; Strewler, G J; Nissenson, R A



Parathyroid hormone-related protein stimulates plasma renin activity via its anorexic effects on sodium chloride intake  

PubMed Central

Parathyroid hormone-related protein (PTHrP) increases renin release from isolated perfused kidneys and may act as an autacoid regulator of renin secretion, but its effects on renin in vivo are unknown. In vivo, PTHrP causes hypercalcemia and anorexia, which may affect renin. We hypothesized that chronically elevated PTHrP would increase plasma renin activity (PRA) indirectly via its anorexic effects, reducing sodium chloride (NaCl) intake and causing NaCl restriction. We infused male Sprague-Dawley rats with the vehicle (control) or 125 ?g PTHrP/day (PTHrP) via subcutaneous osmotic minipumps for 5 days. To replenish NaCl consumption, a third group of PTHrP-infused rats received 0.3% NaCl (PTHrP + NaCl) in their drinking water. PTHrP increased PRA from a median control value of 3.68 to 18.4 ng Ang I·ml?1·h?1 (P < 0.05), whereas the median PTHrP + NaCl PRA value was normal (7.82 ng Ang I·ml?1·h?1, P < 0.05 vs. PTHrP). Plasma Ca2+ (median control: 10.2 mg/dl; PTHrP: 13.7 mg/dl; PTHrP + NaCl: 14.1 mg/dl; P < 0.05) and PTHrP (median control: 0.03 ng/ml; PTHrP: 0.12 ng/ml; PTHrP + NaCl: 0.15 ng/ml; P < 0.05) were elevated in PTHrP- and PTHrP + NaCl-treated rats. Body weights and caloric consumption were lower in PTHrP- and PTHrP + NaCl-treated rats. NaCl consumption was lower in PTHrP-treated rats (mean Na+: 28.5 ± 4.1 mg/day; mean Cl?: 47.8 mg/day) compared with controls (Na+: 67.3 ± 2.7 mg/day; Cl?: 112.8 ± 4.6 mg/day; P < 0.05). NaCl consumption was comparable with control in the PTHrP + NaCl group; 0.3% NaCl in the drinking water had no effect on PRA in normal rats. Thus, our data support the hypothesis that PTHrP increases PRA via its anorexic effects, reducing NaCl intake and causing NaCl restriction.

Atchison, Douglas K.; Westrick, Elizabeth; Szandzik, David L.; Gordish, Kevin L.



Threshold value of serum 25-hydroxyvitamin D concentration in relation to elevated serum parathyroid hormone concentrations in elderly Japanese women.  


This study was designed to determine the threshold value for 25-hydroxyvitamin D [25(OH)D] concentration in relation to elevated serum parathyroid hormone (PTH) concentrations in elderly Japanese women. The subjects were 582 noninstitutionalized, ambulant women who lived in a community in Japan. Serum 25(OH)D concentrations were determined using the Nichols Advantage chemiluminescent assay, and serum intact PTH concentrations were determined with a two-site immunoradiometric assay. Demographic characteristics, calcium intake, and serum 1,25(OH)(2)D levels were also determined. The average age, body mass index (BMI), and calcium intake of the subjects were 74.5 years (SD 4.5), 23.3 kg/m(2) (SD 3.4), and 579 mg/day (SD 248), respectively. The serum log-transformed intact PTH concentration was significantly predicted by the serum 25(OH)D concentration (r = -0.147, P = 0.0004), but not by age, BMI, the serum log-transformed 1,25(OH)(2)D concentration, or the log-transformed calcium intake. Analysis of variance with Dunnett's multiple comparisons showed that mean serum intact PTH concentrations with serum 25(OH)D concentrations less than 30 nmol/l (mean intact PTH = 5.89 pmol/l, P < 0.0001) and in the range 30-39 nmol/l (mean intact PTH = 4.54 pmol/l, P = 0.0067) were significantly higher than mean intact PTH concentrations for serum 25(OH)D concentrations greater than 50 nmol/l (mean intact PTH = 3.65 pmol/l, the baseline level), but the mean serum intact PTH concentration for 25(OH)D concentrations in the range 40-49 nmol/l (mean intact PTH = 3.70 pmol/l, P = 0.9975) was not. We conclude that serum 25(OH)D for ambulant elderly Japanese women should be maintained at 40 nmol/l or higher. PMID:16937272

Nakamura, Kazutoshi; Nashimoto, Mitsue; Tsuchiya, Yasuo; Saito, Toshiko; Nishiwaki, Tomoko; Ueno, Kimiko; Okuda, Yoko; Oshiki, Rieko; Yamamoto, Masaharu



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.



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.



New understanding of the molecular mechanism of receptor-mediated genomic actions of the vitamin D hormone  

Microsoft Academic Search

The nuclear vitamin D receptor (VDR) binds the 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] hormone with high affinity and elicits its actions to regulate gene expression in target cells by binding to vitamin D-responsive elements (VDREs). VDREs in positively controlled genes such as osteocalcin, osteopontin, ?3-integrin, and vitamin D-24-OHase are direct hexanucleotide repeats with a spacer of three nucleotides. The VDR associates with

M. R. Haussler; P. W. Jurutka; J.-C. Hsieh; P. D. Thompson; S. H. Selznick; C. A. Haussler; G. K. Whitfield



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



Effect of switching hepatic enzyme-inducer antiepileptic drug to levetiracetam on bone mineral density, 25 hydroxyvitamin D, and parathyroid hormone in young adult patients with epilepsy.  


We sought to determine the effect of changing phenytoin therapy on bone mineral density (BMD) and 25-hydroxyvitamin D in patients with epilepsy. Of the 90 patients, 54 patients had switched to levetiracetam, 19 patients had stopped, and 17 patients continued taking phenytoin. We proposed a 2-year period to examine 25-hydroxyvitamin D, parathyroid hormone, and BMD. The patients who switched or stopped phenytoin showed a significant increase in BMD of the lumbar spine and left femur, and in 25-hydroxyvitamin D. In contrast, those who continued phenytoin had a significant decrease in BMD at both sites and in 25-hydroxyvitamin D. Patients who were taken off phenytoin and those switching to levetiracetam did not show a significant difference in BMD, 25-hydroxyvitamin D, parathyroid, or calcium at follow-up. Compared with those who continued phenytoin, the BMD was significantly higher in patients switching to levetiracetam and those who stopped using phenytoin. Switching medications may be necessary in some cases to avoid low BMD. PMID:23586623

Phabphal, Kanitpong; Geater, Alan; Limapichat, Kitti; Sathirapanya, Pornchai; Setthawatcharawanich, Suwanna; Leelawattana, Rattana



Aging changes in hormone production  


... are four tiny glands located around the thyroid. Parathyroid hormone affects calcium and phosphate levels, which affect the strength of the bones. Parathyroid hormone levels rise with age, which may contribute to ...


Stimulation of ovine placental transport of calcium and magnesium by mid-molecule fragments of human parathyroid hormone-related protein.  


Perfusion in situ of the placenta of intact or previously parathyroidectomized fetal lambs has been used to assess the ability of three mid-molecule fragments of the human parathyroid hormone-related protein (PTHrP) molecule to stimulate the placental transport of calcium and magnesium. PTHrP(67-86 amide) was most effective but some activity was also shown by PTHrP(75-86 amide) and by PTHrP (75-84) in decreasing order. This placental action of PTHrP(67-86 amide) was rapid and could be observed using the placenta from an intact fetus, whereas it was necessary to use the placenta from a previously parathyroidectomized fetus to demonstrate stimulation of placental calcium transport by PTHrP(1-84). PTHrP(67-86 amide) may resemble the molecule that activates the placental calcium pump. PMID:2223059

Care, A D; Abbas, S K; Pickard, D W; Barri, M; Drinkhill, M; Findlay, J B; White, I R; Caple, I W



A new immunoenzymometric assay for bioactive N-terminal human parathyroid hormone fragments and its application in pharmacokinetic studies in dogs.  


Advances in the treatment of clinical disorders of mineral in homeostatis and metabolic bone disease with intact parathyroid hormone 1-84 or one of the biologically active N-terminal fragments require a precise and sensitive measurement in serum. Therefore, a two-site immunoenzymometric assay for the quantitative determination of bioactive hPTH-1-37 (human parathyroid hormone) at picomolar concentrations was developed. Monoclonal antibodies (mAB) against hPTH-1-37 were raised by hybridoma cells in serum-free cell culture. Furthermore, sequence-specific polyclonal antibodies were obtained by immunisation of rabbits using multiple antigenic peptides (MAP) representing the conspicuous regions of the primary structure of hPTH-1-37. The polyclonal and monoclonal antibodies were characterised by epitope mapping. The combination of a monoclonal antibody (13C63/5) recognising hPTH fragment 16-24 with a polyclonal antibody (k2) showing a predominant binding sequence at hPTH-1-5 led to a sandwich assay specific for N-terminally intact and therefore biologically active hPTH. The validated assay ranging from 4 to 1000 pmol/l was applied to pharmacokinetic studies of hPTH-1-37. After s.c. administration of 30 mu g/kg in 5 beagles, the maximum serum concentrations of hPTH-1-37 ranging at 2139 +/- 857 pmol/l were observed 45 min after the injection. Clearance of the peptide calculated from the exponential disappearance curve was 32.0 +/- 9.1 ml/min/kg with a mean t1/2 of 37 +/- 10 min. PMID:9541733

Mägerlein, M; Hock, D; Adermann, K; Müller-Beckmann, B; Neidlein, R; Forssmann, W G; Stein, K



Solvent independent conformational propensities of [1,2,3]triazolyl-bridged parathyroid hormone-related peptide-derived cyclo-nonapeptide analogues.  


The recently introduced Cu(I)-catalyzed azide-alkyne 1,3-dipolar Huisgen cycloaddition as a prototypic "click chemistry reaction" presented an opportunity for introducing the 1,4-disubstituted-[1,2,3]triazolyl moiety as a new isostere for peptide bonds in the backbone. Previous study in our lab focused on the synthesis of a model i-to-i+4 side chain-to-side chain 1,4- and 4,1-disubstituted-[1,2,3]triazolyl-bridged cyclo-nonapeptide I (Scheme 1) as analogues of its structurally related helical i-to-i+4 lactam-bridged cyclo-nonapeptide [Lys¹³ (&¹), Asp¹? (&²)]parathyroid hormone related peptide (PTHrP)(11-19)NH? (1) a truncated version of the ?-helical and potent parathyroid hormone receptor 1 agonist [Lys¹³ (&¹), Asp¹? (&²)]PTHrP(1-34)NH?, (2,3) N(?) -Ac-Lys-Gly-Lys(&¹)-Ser-Ile-Gln-Asp(&²)-Leu-Arg-NH?]. Systematic [1,2,3]triazolyl-containing bridge structure-conformation relationship studies in hexafluoroacetone/water mixture included incorporation of bridges varied in size and position and orientation of the triazolyl ring within the bridge. These studies revealed that the size of methylene bridge flanking triazolyl moiety is critical to reproduce in the heterodetic cyclo-nonapeptides. The conformational features of the analogues cyclo-nonapeptide in which Lys¹³ and Asp¹? are bridged by the isosteric lactam. Here, we extend our conformational analysis to dimethyl sulfoxide/water mixture in an effort to characterize inherent conformational properties of the heterodetic cyclopeptides that are solvent independent. Our present study shows that the physicochemical properties of the structure-supporting solvent cannot override the effect of the size of methylene bridge to form helical mimetic structures. Moreover, we prove that [1,2,3]triazolyl ring is not a simple bioisostere of lactam bond, but it affects the secondary structure of the peptide, in relation to its positioning orientation. PMID:23203759

Scrima, Mario; Grimaldi, Manuela; Di Marino, Sara; Testa, Chiara; Rovero, Paolo; Papini, Anna Maria; Chorev, Michael; D'Ursi, Anna Maria



Association of high vitamin d status with low circulating thyroid-stimulating hormone independent of thyroid hormone levels in middle-aged and elderly males.  


Background. A recent study has reported that high circulating 25-hydroxyvitamin D [25(OH)D] is associated with low circulating thyroid-stimulating hormone (TSH) levels, but only in younger individuals. The goal of the present study was to explore the relationship between vitamin D status and circulating TSH levels with thyroid autoimmunity and thyroid hormone levels taken into consideration in a population-based health survey of middle-aged and elderly individuals. Methods. A total of 1,424 Chinese adults, aged 41-78?years, were enrolled in this cross-sectional study. Serum levels of 25(OH)D, TSH, thyroid hormones, and thyroid autoantibodies were measured. Results. The prevalence of vitamin D insufficiency was 94.29% in males and 97.22% in females, and the prevalence of vitamin D deficiency was 55.61% in males and 69.64% in females. Vitamin D status was not associated with positive thyroid autoantibodies after controlling for age, gender, body mass index, and smoking status. Higher 25(OH)D levels were associated with lower TSH levels after controlling for age, FT4 and FT3 levels, thyroid volume, the presence of thyroid nodule(s), and smoking status in males. Conclusion. High vitamin D status in middle-aged and elderly males was associated with low circulating TSH levels independent of thyroid hormone levels. PMID:24693286

Zhang, Qingqing; Wang, Zhixiao; Sun, Min; Cao, Mengdie; Zhu, Zhenxin; Fu, Qi; Gao, Yuan; Mao, Jia; Li, Yanyun; Shi, Yun; Yang, Fan; Zheng, Shuai; Tang, Wei; Duan, Yu; Huang, Xiaoping; He, Wei; Yang, Tao



Phenytoin induced vitamin d deficiency presenting as proximal muscle weakness  

Microsoft Academic Search

A 6-year-old girl presented with proximal muscle weakness of lower limbs. She was receiving phenytoin for epilepsy for 2 years.\\u000a Serum phenytoin level was within therapeutic range. Serum 25(OH) vitamin D was low (5ng\\/mL) and serum parathyroid hormone\\u000a level was high. After administration of oral vitamin D, muscle weakness improved and vitamin D level increased to 39.11ng\\/mL.\\u000a Proximal muscle weakness

M. M. A. Faridi; Anju Aggarwal



[Essential parathyroid cysts: a misleading lesion].  


Though a rare lesion, non-functioning parathyroid cyst is of clinical significance because it usually mimics a thyroid nodule. The cyst can be ectopic in location and therefore constitutes a differential diagnosis to a bronchial or thymic cyst. Two recent cases of non-functioning parathyroid assay are reported. Needle puncture with estimation of the level of parathyroid hormone in the aspirate allows the diagnosis to be made before surgery. PMID:11109882

Braccini, F; Epron, J P; Roux, C; Gabert, K; Richard-Vitton, T; Korchia, D; Dessi, P; Thomassin, J M




PubMed Central

There is growing recognition that traumatic brain injury (TBI) is a highly variable and complex systemic disorder that is refractory to therapies that target individual mechanisms. It is even more complex in the elderly, in whom frailty, prior comorbidities, altered metabolism, and a long history of medication use are likely to complicate the secondary effects of brain trauma. Progesterone, one of the few neuroprotective agents that has shown promise for the treatment of acute brain injury, is now in national and international Phase III multi-center trial. New findings show that vitamin D hormone (VDH) and vitamin D deficiency in aging (and across the developmental spectrum) may interact with progesterone and TBI treatment. This paper reviews the use of progesterone and VDH as biologics based therapies and recent studies showing that the combination of progesterone and VDH may promote better functional outcomes than either treatment independently.

Stein, Donald G.; Cekic, Milos M.



Vitamin D-Binding Protein and Vitamin D Status of Black Americans and White Americans  

PubMed Central

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

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



Parathyroid Cancer  

PubMed Central

Parathyroid cancer is an uncommon malignancy and rare cause of primary hyperparathyroidism with a high morbidity and patient death in advanced cases usually resulting from intractable hypercalcemia. Inactivation of the HRPT2/CDC73 gene, encoding the putative tumor suppressor protein parafibromin and discovered in the context of the hyperparathyroidism-jaw tumor syndrome (HPT-JT), is a common, somatic genetic event in most parathyroid cancers. Some 25% of patients with apparently sporadic parathyroid cancer carry germline HRPT2/CDC73 mutation. Germline DNA analysis for HRPT2/CDC73 mutation is recommended in all patients with parathyroid cancer because of the potential benefit for offspring and other first-degree relatives. The histopathologic diagnosis of parathyroid cancer is non-specific unless vascular, lymphatic, capsular or soft tissue invasion are seen, or metastases are clinically evident. Immunohistochemical analysis of parathyroid tumors for loss of parafibromin expression offers promise as a diagnostic tool. En bloc tumor resection offers the highest chance of cure in patients with suspected parathyroid carcinoma. No adjuvant chemotherapy regimen has yet proven effective, and the role of local adjuvant radiotherapy is being evaluated. Metastatic disease can be palliated with surgical debulking. Medical therapy with the calcimimetic cinacalcet and bisphosphonates can ameliorate hypercalcemia in patients with inoperable disease.

Sharretts, John M.; Kebebew, Electron



Long-term evaluation of patients with primary parathyroid hyperplasia managed by total parathyroidectomy and heterotopic autotransplantation.  

PubMed Central

Since 1973, we have performed total parathyroidectomy and forearm parathyroid autotransplantation in 36 patients with generalized (four gland) primary parathyroid hyperplasia. Twenty (56%) patients had nonfamilial parathyroid hyperplasia (NFPH) and 16 (44%) patients had familial parathyroid hyperplasia (FPH). Twenty-one patients (Group A) were undergoing operation for the first time and 15 (Group B) were having either second, third or fourth re-explorations for persistent hyperparathyroidism. All patients in Group A and nine patients in Group B had parathyroid resection and immediate autotransplantation as a single procedure. Six Group B patients had hyperfunctioning parathyroid tissue resected, cryopreserved, and subsequently grafted when it was evident that they had been rendered aparathyroid. A sustained differential elevation (13.7 fold +/- 2.7) of parathyroid hormone was detected in the antecubital vein of the grafted compared to the nongrafted arm in 35 (97%) patients. Two (5.6%) of the 36 patients (both with FPH; one Group A and one Group B) required permanent oral calcium and vitamin D replacement therapy and one (3%) patient (NFPH: Group A) had persistent hypercalcemia postoperatively, presumably due to a supernumerary gland. The remaining 33 (92%) patients became normocalcemia after surgery and 23 (70%) of them remained so. Ten (30%) of the 33 patients developed recurrent graft dependent hyperparathyroidism. Eight patients were from the group with FPH (8/14, 57%) and two were from the group with NFPH (2/19, 11%)(FPH vs. NFPH, p < 0.005). Because of symptoms of hypercalcemia or a serum calcium concentration exceeding 11 mg/dl, partial graft resection was performed in five patients and four became normocalcemic. Patients with generalized primary parathyroid hyperplasia may be difficult to cure, especially if the disease is familial. The technique of total parathyroidectomy and heterotopic autotransplantation of fresh or cryopreserved parathyroid tissue offers distinct advantages over alternative techniques.

Wells, S A; Farndon, J R; Dale, J K; Leight, G S; Dilley, W G



Conflicting actions of parathyroid hormone-related protein and serum calcium as regulators of 25-hydroxyvitamin D(3)-1 alpha-hydroxylase expression in a nude rat model of humoral hypercalcemia of malignancy.  


In patients with humoral hypercalcemia of malignancy (HHM), serum levels of 1,25-dihydroxyvitamin D (1,25(OH)(2)D) are generally low, although the pathophysiology of the impaired vitamin D metabolism is not fully understood. In the present study, we have investigated vitamin D metabolism in our newly developed rat model of HHM in which a human infantile fibrosarcoma producing parathyroid hormone-related protein (PTHrP), named OMC-1, was inoculated s.c. into athymic nude rats. In OMC-1-bearing rats, the serum concentration of 1,25(OH)(2)D was markedly reduced when the animals exhibited severe hypercalcemia (Ca > or =15 mg/dl), while it was rather elevated in those with mild hypercalcemia. To further examine whether serum Ca levels affect 1,25(OH)(2)D concentration, we administered bisphosphonate YM529 to OMC-1-bearing rats when they exhibited severe hypercalcemia. The restoration of the serum Ca level by administration of YM529 was accompanied by a marked increase in the 1,25(OH)(2)D level, suggesting that the serum Ca level itself plays an important role in the regulation of the 1,25(OH)(2)D level in these rats. On the other hand, when the OMC-1-bearing rats were treated with a neutralizing antibody against PTHrP, serum 1,25(OH)(2)D levels remained low despite the reduction in serum Ca levels. Expression of 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase) in kidney was decreased in OMC-1-bearing rats with severe hypercalcemia, and markedly enhanced after treatment with bisphosphonate. This enhancement in 1 alpha-hydroxylase expression was not observed after treatment with the antibody against PTHrP. These results suggest that PTHrP was responsible for the enhanced expression of 1 alpha-hydroxylase in YM529-treated rats, and that hypercalcemia played a role in reducing the serum 1,25(OH)(2)D level in OMC-1-bearing rats by suppressing the PTHrP-induced expression of the 1 alpha-hydroxylase gene. PMID:11691644

Michigami, T; Yamato, H; Suzuki, H; Nagai-Itagaki, Y; Sato, K; Ozono, K



Effects of Treatment of Ovariectomized Adult Rhesus Monkeys with Parathyroid Hormone 1-84 for 16 Months on Trabecular and Cortical Bone Structure and Biomechanical Properties of the Proximal Femur  

Microsoft Academic Search

Treatment of monkeys and humans with parathyroid hormone (PTH) 1-84 stimulates skeletal remodeling, which increases trabecular\\u000a (Tb) bone mineral density (BMD) but decreases cortical (Ct) BMD at locations where these bone types predominate. We report\\u000a the effects of daily PTH treatment (5, 10, or 25 ?g\\/kg) of ovariectomized (OVX) rhesus monkeys for 16 months on bone structure\\u000a and biomechanical properties

J. Fox; M. A. Miller; R. R. Recker; C. H. Turner; S. Y. Smith



Doxercalciferol, a pro-hormone of Vitamin D, prevents the development of cardiac hypertrophy in rats  

PubMed Central

Background Activated vitamin D analog, paricalcitol, has been shown to attenuate the development of cardiac hypertrophy in Dahl salt sensitive (DSS) rats. To determine whether an anti-hypertrophic effect is class specific, we tested if doxercalciferol (a pro-hormone vitamin D2 analog) could also attenuate the development of cardiac hypertrophy in DSS rats. Methods and Results Male DSS rats were fed a high salt (HS) diet for 6 weeks beginning at 6 weeks of age. Doxercalciferol was administered intraperitoneally (i.p.) at 150ng, 3 times a week (Mon, Wed, Fri) for six weeks. Pathological and echocardiographic findings demonstrated that rats on HS diet with doxercalciferol administration had significant decrease in cardiac hypertrophy and improved cardiac function compared to the HS + vehicle. In addition, there was a significant decrease in plasma brain natriuretic peptide (BNP) level and tissue atrial natriuretic factor (ANF) mRNA level with doxercalciferol treatment. Doxercalciferol also significantly reduced the level of protein kinase C-? (PKC?) suggesting that PKC-mediated cardiac hypertrophy may be associated with vitamin D deficiency. Conclusions Administration of doxercalciferol attenuated the development of HS diet induced cardiac hypertrophy and cardiac dysfunction in DSS rats.

Choi, Jun H.; Ke, Qingen; Bae, Soochan; Lee, Ji Yoo; Kim, Yu Jin; Kim, Ui Kyoung; Arbeeny, Cynthia; Thadhani, Ravi; Kang, Peter M.




PubMed Central

Parathyroid hormone receptor 2 (PTH2R) and its ligand, tuberoinfundibular peptide of 39 residues (TIP39) constitute a neuromodulator system implicated in endocrine and nociceptive regulations. We now describe the presence and distribution of the PTH2R and TIP39 in the brain of primates using a range of tissues and ages from macaque and human brain. In situ hybridization histochemistry of TIP39 mRNA, studied in young macaque brain, due to its possible decline beyond late postnatal ages, was present only in the thalamic subparafascicular area and the pontine medial paralemniscal nucleus. In contrast in situ hybridization histochemistry in macaque identified high levels of PTH2R expression in the central amygdaloid nucleus, medial preoptic area, hypothalamic paraventricular and periventricular nuclei, medial geniculate, and the pontine tegmentum. PTH2R mRNA was also detected in several human brain areas by RT-PCR. The distribution of PTH2R-immunoreactive fibers in human, determined by immunocytochemistry, was similar to that in rodents including dense fiber networks in the medial preoptic area, hypothalamic paraventricular, periventricular and infundibular (arcuate) nuclei, lateral hypothalamic area, median eminence, thalamic paraventricular nucleus, periaqueductal gray, lateral parabrachial nucleus, nucleus of the solitary tract, sensory trigeminal nuclei, medullary dorsal reticular nucleus, and dorsal horn of the spinal cord. Co-localization suggested that PTH2R fibers are glutamatergic, and that TIP39 may directly influence hypophysiotropic somatostatin containing and indirectly influence corticotropin releasing-hormone containing neurons. The results demonstrate that TIP39 and the PTH2R are expressed in the brain of primates in locations that suggest involvement in regulation of fear, anxiety, reproductive behaviors, release of pituitary hormones, and nociception.

Bago, Attila G.; Dimitrov, Eugene; Saunders, Richard; Seress, Laszlo; Palkovits, Miklos; Usdin, Ted B.; Dobolyi, Arpad



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.

Mishra, Ankur; Newman, David





... vitamins D and K. People who eat a vegetarian diet may need to take a vitamin B12 supplement. Each vitamin has specific jobs. If you have low levels of certain vitamins, you may get health problems. For example, if you don't get ...


Intrathyroidal parathyroid hyperplasia in tertiary hyperparathyroidism.  


We report herein a case of intrathyroidal parathyroid hyperplasia in a patient with tertiary hyperparathyroidism. The patient was recommended for parathyroidectomy due to sustained hypercalcemia after kidney transplantation. Preoperative radiologic evaluations showed a benign-looking thyroid mass and three enlarged parathyroid glands. Intraoperative intact parathyroid hormone (iPTH) level and frozen biopsy results indicated a missed parathyroid gland after immediate subtotal parathyroidectomy. Then, a secondary partial resection of thyroid including the thyroid nodule was performed. An excised intrathyroid nodule was diagnosed to be parathyroid hyperplasia by frozen biopsy, and intraoperative iPTH level abruptly decreased. A benign-looking thyroidal mass in patients with secondary or tertiary hyperparathyroidism should be carefully evaluated considering the possibility of an intrathyroidal parathyroid hyperplasia. PMID:24964443

Kim, Byung Seup; Ryu, Han Suk; Kang, Kyung Ho; Park, Sung Jun



Vitamin D supplementation has no effect on insulin resistance assessment in women with polycystic ovary syndrome and vitamin D deficiency.  


Insulin resistance is one of the most common features of polycystic ovary syndrome (PCOS). Some studies suggest that vitamin D deficiency may have a role in insulin resistance; thus, the aim of the current study was to determine the effect of vitamin D supplementation on insulin resistance in women with PCOS and a vitamin D deficiency. We hypothesized that vitamin D supplementation would lower the glucose level and insulin resistance in women with PCOS and a vitamin D deficiency. The current study was a randomized, placebo-controlled, double-blinded trial with 50 women with PCOS and a vitamin D deficiency, 20 to 40 years old, assigned to receive 3 oral treatments consisting of 50,000 IU of vitamin D? or a placebo (1 every 20 days) for 2 months (vitamin D, n = 24; placebo, n = 26). The fasting blood glucose, insulin, 25-hydroxyvitamin D, and parathyroid hormone levels, as well as the homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were measured at baseline and after treatment. In the vitamin D group, the serum level of 25-hydroxyvitamin D increased (6.9 ± 2.8 to 23.4 ± 6.1 ng/mL, P < .0001), and the parathyroid hormone level decreased (70.02 ± 43.04 to 50.33 ± 21.99 ? IU/mL, P = .02). There were no significant changes in the placebo group. There was a significant increase in insulin secretion in the vitamin D group (P = .01), but this was not significant compared with the placebo group. The fasting serum insulin and glucose levels and the insulin sensitivity and homeostasis model assessment of insulin resistance did not change significantly by the end of the study. We were not able to demonstrate the effect of vitamin D supplementation on insulin sensitivity and insulin resistance in women with PCOS and vitamin D deficiency. PMID:22464806

Ardabili, Hania R; Gargari, Bahram P; Farzadi, Laya



Substernal oxyphil parathyroid adenoma producing PTHrP with hypercalcemia and normal PTH level  

PubMed Central

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. Functioning oxyphil parathyroid adenoma is an uncommon histological form, seldom causing primary hyperparathyroidism. Parathyroid adenoma with hypercalcemia exhibiting normal parathyroid hormone level is rare. An incidence of 5% to 33% has been documented in the literature; no etiologic explanation has been given. In 1987, parathyroid-hormone-related peptide was isolated as a causative factor of humeral hypercalcemia of malignancy. The presence of parathyroid-hormone-related peptide in parathyroid tissue under normal and pathological conditions has been described in the literature; however, its role in causing hyperparathyroidism has not yet been defined. Case presentation We present a case of persistent hypercalcemia with a normal level of intact-parathyroid hormone due to a substernal parathyroid adenoma, treated with radioguided parathyroidectomy. The final histological diagnosis was oxyphil adenoma, positive for parathyroid-hormone-related peptide antigens. Conclusion In clinical practice, this atypical biochemical presentation of primary hyperparathyroidism should be considered in the differential diagnosis of hypercalcemia. The parathyroid-hormone-related peptide should be considered not only in the presence of malignancy.

Gurrado, Angela; Marzullo, Andrea; Lissidini, Germana; Lippolis, Agostino; Rubini, Domenico; Lastilla, Gaetano; Testini, Mario



Parathyroid Hormone-Related Protein (PTHrP): A Key Regulator of Life/Death Decisions by Tumor Cells with Potential Clinical Applications  

PubMed Central

Parathyroid hormone-related protein (PTHrP), classically regarded as the mediator of the humoral hypercalcemia of malignancy syndrome, is a polyhormone that undergoes proteolytic processing into smaller bioactive forms. These bioactive forms comprise an N-terminal-as well as midregion-and C-terminal peptides, which have been shown to regulate various biological events, such as survival, proliferation and differentiation, in diverse cell model systems, both normal and pathological. A number of experimental data have demonstrated that PTHrP is also able to modulate tumor-relevant phenotypic expressions, thereby playing a role in early and advanced tumorigenesis, and in the response to treatment. In particular, interest has mainly been focused on the effects of PTHrP on cell proliferation/apoptosis, migration and invasion, which are the main roles involved in cancer development in vivo. The objective of this review is to discuss collectively the literature data on the molecular and biochemical basis of the mechanisms underlying the different, and sometimes opposite, effects exerted by PTHrP on various neoplastic cytotypes, with some final comments on both present and potential utilization of PTHrP as a target for anti-cancer therapy.

Luparello, Claudio



Calcium mass balance and behavior of intact immunoreactive parathyroid hormone in acetate-free biofiltration: acute and one-year evaluation.  


The present study evaluated calcium mass balance (MB) during acetate-free biofiltration (AFB) with a dialysate calcium concentration of 2 mmol/l and different ultrafiltration rates (UF; 42.5 ml/min in schedule 1 and 48.5 ml/min in schedule 3), and with a calcium concentration of 1.75 mmol/l but an UF of 43 ml/min (schedule 2). We also examined the effects of these schedules on the behavior of intact parathyroid hormone (I-PTH). AFB according to schedule 1 and 3 achieve a positive calcium MB (8.49 +/- 1.56 and 5.59 +/- 1.06 mmol, respectively), while in schedule 2 calcium MB merely balanced (0.07 +/- 2.29 mmol/l). A significant acute intradialytic I-PTH decrease was observed with all schedules; after 1 month, however, predialytic PTH values were unchanged in schedules 1 and 3, but worsening was noted in schedule 2. Subsequently, AFB was performed for 12 months employing a dialytic schedule (No. 1) involving a positive calcium balance. A year later I-PTH was significantly lower, thus proving that AFB may play an additional part in controlling secondary hyperparathyroidism. PMID:7826579

de Vincenzi, A; Bellazzi, R; Santagostino, M; Romanini, D; Nai, M; Gazo, A; Bacchella, L; Gini, A



Effectors of cyclic adenosine 5'-monophosphate up-regulating-oxytocin receptors in rabbit amnion cells: isoproterenol, parathyroid hormone-related protein, and potentiation by cortisol.  


Forskolin (FSK; an activator of adenylyl cyclase) and cortisol synergistically increase the concentration of oxytocin receptors (OTRs) in rabbit amnion cells. The aims of this study were to characterize potential physiological regulators of OTR concentrations acting through adenylyl cyclase and to clarify the mechanisms of potentiation by cAMP and cortisol. Both isoproterenol (ISO) and parathyroid hormone-related protein (PTHrP) elevated amnion cell cAMP levels and OTR concentrations. The effects of ISO and PTHrP on OTR were potentiated by cortisol. Cortisol had no effect on the ability of ISO or PTHrP to stimulate adenylyl cyclase activity, and cAMP did not affect the number or affinity of glucocorticoid receptors in whole cells or in cytosol. Adenylyl cyclase activation, however, caused conversion of mifepristone (RU486) from a glucocorticoid antagonist to agonist. Thus, mifepristone elevated OTR receptor concentrations in the presence of FSK. In contrast, a structurally related glucocorticoid antagonist, onapristone (ZK98 299), was unaffected by cAMP. Because glucocorticoid receptors bound to mifepristone are capable of interacting with DNA, whereas onapristone-occupied receptors are not, we conclude that cAMP affects glucocoticoid receptor-DNA interactions, accounting for the synergistic effects of cAMP and cortisol on OTRs. PMID:8527507

Jeng, Y J; Hinko, A; Soloff, M S



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


Excess parathyroid hormone (PTH) has long been considered detrimental to the health of patients with end-stage renal disease. PTH has been implicated as a multisystem uremic toxin, and hyperparathyroidism can be a debilitating complication in dialyzed patients. We have studied prospectively the relationship of enrollment serum intact PTH and various demographic characteristics and other biochemical parameters to all-cause mortality in 345 hemodialysis (HD) and 277 peritoneal dialysis (PD) patients. We monitored the patients for 14 years. Observed survival and survival after adjustment for age, race, gender, months on dialysis at enrollment, diabetic status, and nutritional markers were significantly better for patients with enrollment PTH greater than 200 pg/mL than for patients with PTH 65 to 199 pg/mL and patients with PTH less than 65 pg/mL. Enrollment serum PTH was an independent predictor of survival in HD and PD patients. For HD patients, age and months on HD at enrollment were associated inversely with PTH level, whereas black race, creatinine, and phosphorus were associated directly with PTH. For PD patients, age, diabetes, and months on PD at enrollment were inverse predictors, whereas black race, albumin, creatinine, and phosphorus were associated positively with PTH. Lower than expected levels of PTH in uremic patients is associated with increased mortality. We hypothesize that inadequate protein intake or phosphorus intake or both result in impaired development of the expected secondary hyperparathyroidism and in the excess mortality risk inherent with malnutrition. PMID:11728974

Avram, M M; Mittman, N; Myint, M M; Fein, P



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

SciTech Connect

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

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



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

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



Inhibition of Sca-1-Positve Skeletal Stem Cell Recruitment by Alendronate Blunts the Anabolic Effects of Parathyroid Hormone on Bone Remodeling  

PubMed Central

SUMMARY The anabolic effects of parathyroid hormone (PTH) on bone formation are impaired by concurrent use of anti-resorptive drugs. We found that the release of active transforming growth factor (TGF)-?1 during osteoclastic bone resorption is inhibited by alendronate. We showed that mouse Sca-1-positive (Sca-1+) bone marrow stromal cells are a skeletal stem cell subset, which are recruited to bone remodeling sites by active TGF-?1 in response to bone resorption. Alendronate inhibits the release of active TGF-?1 and the recruitment of Sca-1+ skeletal stem cells for the bone formation. The observation was validated in a Tgfb1?/? mouse model, in which the anabolic effects of PTH on bone formation are diminished. The PTH-stimulated recruitment of injected mouse Sca-1+ cells to the resorptive sites was inhibited by alendronate. Thus, inhibition of active TGF-?1 release by alendronate reduces the recruitment of Sca-1+ skeletal stem cells and impairs the anabolic action of PTH in bone.

Wu, Xiangwei; Pang, Lijuan; Lei, Weiqi; Lu, William; Li, Jun; Li, Zhaoyang; Frassica, Frank J.; Chen, Xueling; Wan, Mei; Cao, Xu



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.

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



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

PubMed Central

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



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


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



Interaction of a farnesylated protein with renal type IIa Na/Pi co-transporter in response to parathyroid hormone and dietary phosphate.  

PubMed Central

Treatment with PTH (parathyroid hormone) or a high-P(i) diet causes internalization of the type IIa sodium-dependent phosphate (Na/P(i) IIa) co-transporter from the apical membrane and its degradation in the lysosome. A dibasic amino acid motif (KR) in the third intracellular loop of the co-transporter is essential for protein's PTH-induced retrieval. To elucidate the mechanism of internalization of Na/P(i) IIa, we identified the interacting protein for the endocytic motif by yeast two-hybrid screening. We found a strong interaction of the Na/P(i) IIa co-transporter with a small protein known as the PEX19 (human peroxisomal farnesylated protein; PxF, Pex19p). PEX19 can bind to the KR motif, but not to a mutant with this motif replaced with NI residues. PEX19 is highly expressed in mouse and rat kidney. Western blot analysis indicates that PEX19 is located in the cytosolic and brush-border membrane fractions (microvilli and the subapical component). Overexpression of PEX19 stimulated the endocytosis of the Na/P(i) IIa co-transporter in opossum kidney cells in the absence of PTH. In conclusion, the present study indicates that PEX19 may be actively involved in controlling the internalization and trafficking of the Na/P(i) IIa co-transporter.

Ito, Mikiko; Iidawa, Sachi; Izuka, Michiyo; Haito, Sakiko; Segawa, Hiroko; Kuwahata, Masashi; Ohkido, Ichiro; Ohno, Hiroshi; Miyamoto, Ken-Ichi



Vitamin D and African Americans.  


Vitamin D insufficiency is more prevalent among African Americans (blacks) than other Americans and, in North America, most young, healthy blacks do not achieve optimal 25-hydroxyvitamin D [25(OH)D] concentrations at any time of year. This is primarily due to the fact that pigmentation reduces vitamin D production in the skin. Also, from about puberty and onward, median vitamin D intakes of American blacks are below recommended intakes in every age group, with or without the inclusion of vitamin D from supplements. Despite their low 25(OH)D levels, blacks have lower rates of osteoporotic fractures. This may result in part from bone-protective adaptations that include an intestinal resistance to the actions of 1,25(OH)2D and a skeletal resistance to the actions of parathyroid hormone (PTH). However, these mechanisms may not fully mitigate the harmful skeletal effects of low 25(OH)D and elevated PTH in blacks, at least among older individuals. Furthermore, it is becoming increasingly apparent that vitamin D protects against other chronic conditions, including cardiovascular disease, diabetes, and some cancers, all of which are as prevalent or more prevalent among blacks than whites. Clinicians and educators should be encouraged to promote improved vitamin D status among blacks (and others) because of the low risk and low cost of vitamin D supplementation and its potentially broad health benefits. PMID:16549493

Harris, Susan S



Improvement of calcium balance by Fructus Ligustri Lucidi extract in mature female rats was associated with the induction of serum parathyroid hormone levels.  


Fructus Ligustri Lucidi (FLL) is a commonly prescribed herb in many kidney-tonifying Traditional Chinese Medicinal formulae for the treatment of osteoporosis. The present study aimed to identify the active fractions in FLL and to characterise its effects on Ca balance, calciotropic hormone levels as well as bone properties in mature female rats fed diets containing different levels of Ca. In the present study, 4-month-old Sprague-Dawley female rats were treated with either FLL ethanol extract (EE), ethyl acetate-soluble fraction of EE (EAF), water-soluble fraction of EE (WF) or their vehicle for 12 weeks on a medium-Ca diet (MCD, 0·6 % Ca, 0·65 % P). Then, the Sprague-Dawley female rats treated with WF or its vehicle for 12 weeks were fed diets containing different levels of dietary Ca (low-Ca diet (LCD), 0·1 % Ca, 0·65 % P; MCD; high-Ca diet (HCD), 1·2 % Ca, 0·65 % P). The results demonstrated that WF from EE but not EAF exerted a prominent effect on Ca balance by inhibiting urinary and faecal Ca excretion. WF significantly increased Ca balance in rats fed MCD or HCD with an associated increase in serum parathyroid hormone (PTH) levels. WF did not alter bone mineral density or bone mineral content of the tibia in all the rats fed with different levels of dietary Ca. In conclusion, WF was responsible for the positive actions of FLL on Ca absorption and balance. The regulation of Ca balance by WF might involve its action in stimulating PTH production in the mature female rats. PMID:22018100

Dong, Xiao-Li; Zhao, Ming; Wong, Kwun-Kit; Che, Chun-Tao; Wong, Man-Sau



Parathyroid Hormone Signaling via G?s Is Selectively Inhibited by an NH2-Terminally Truncated G?s: Implications for Pseudohypoparathyroidism  

PubMed Central

Pseudohypoparathyroid patients have resistance predominantly to parathyroid hormone (PTH), and here we have examined the ability of an alternative G?s-related protein to inhibit G?s activity in a hormone-selective manner. We tested whether the G/VAS exon A/B-derived NH2-terminally truncated (Tr) ?s protein alters stimulation of adenylate cyclase by the PTH receptor (PTHR1), the thyroid-stimulating hormone (TSH) receptor (TSHR), the ?2-adrenergic receptor (?2AR), or the AVP receptor (V2R). HEK293 cells cotransfected with receptor and full-length (FL) G?s±Tr ±s protein expression vectors were stimulated with agonists (PTH [10?7 to 10?9 M], TSH [1 to 100 mU], isoproterenol [10?6 to 10?8M], or AVP [10?6 to 10?8M]). Following PTH stimulation, HEK293 cells cotransfected with PTHR1 + FL G?s + Tr ?s had a significantly lower cAMP response than those transfected with only PTHR1 + FL G?s. Tr ?s also exerted an inhibitory effect on the cAMP levels stimulated by TSH via the TSHR but had little or no effect on isoproterenol or AVP acting via ?2AR or V2R, respectively. These differences mimic the spectrum of hormone resistance in pseudohypoparathyroidism type 1a (PHP-1a) and type 1b (PHP-1b) patients. In opossum kidney (OK) cells, endogenously expressing the PTHR1 and ?2AR, the exogenous expression of Tr ?s at a level similar to endogenous FL G?s resulted in blunting of the cAMP response to PTH, whereas that to isoproterenol was unaltered. A pseudopseudohypoparathyroid patient with Albright hereditary osteodystrophy harbored a de novo paternally inherited M1l G?s mutation. Similar maternally inherited mutations at the initiation codon have been identified previously in PHP-1a patients. The M1l ?s mutant (lacking the first 59 amino acids of G?s) blunted the increase in cAMP levels stimulated via the PTHR1 in both HEK293 and OK cells similar to the Tr ?s protein. Thus NH2-terminally truncated forms of G?s may contribute to the pathogenesis of pseudohypoparathyroidism by inhibiting the activity of G?s itself in a GPCR selective manner.

Puzhko, Svetlana; Goodyer, Cynthia Gates; Kerachian, Mohammad Amin; Canaff, Lucie; Misra, Madhusmita; Juppner, Harald; Bastepe, Murat; Hendy, Geoffrey N



Nuclear medicine imaging in a case of hyperfunctioning parathyroid carcinoma associated with a parathyroid adenoma.  


This report describes a rare case of parathyroid carcinoma associated with an adenoma. Nuclear imaging provided the most specific information about localization of the primary carcinoma and cervical metastasis, but failed to demonstrate evidence of a parathyroid adenoma. This could be explained by a partial inhibition of hormonal biosynthesis due to the high level of circulating parathormone produced by the carcinoma. PMID:8521661

Ceriani, L; Giovanella, L C; Salvadore, M; Roncari, G



Parathyroid carcinoma.  


Parathyroid carcinoma is a rare cause of hypercalcaemia due to primary hyperparathyroidism. Ninety five percent of parathyroid carcinomas are functional tumours. Surgery is the only potential curative treatment. This is a case of a 53 years lady, who presented with pathological fracture of femur, hypercalcaemia, deranged renal functions, change in voice, difficulty in swallowing and markedly raised parathormone levels. Doppler ultrasound localized an irregular mass at right lower gland. SESTAMIBI scan showed probability of adenoma in the region of right lower thyroid pole. Intra-operatively, tumour was found stuck to esophagus and right recurrent laryngeal nerve passing through it. Enlarged parathyroid gland was removed in toto along with the recurrent laryngeal nerve, right thyroid lobe and its isthmus. PMID:23217487

Gauhar, Tooba Mahmud; Shahzad, Noman; Mahmud, Tayyaba; Khwaja, Muhammad Azim



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

PubMed Central

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

Luong, Khanh vinh quoc; Nguyen, Lan Thi Hoang



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


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

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



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

PubMed Central

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

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



Mechanical stimulation and intermittent parathyroid hormone treatment induce disproportional osteogenic, geometric, and biomechanical effects in growing mouse bone  

PubMed Central

Mechanical loading and intermittent parathyroid (iPTH) treatment are both osteoanabolic stimuli, and are regulated by partially overlapping cellular signaling pathways. iPTH has been shown clinically to be effective in increasing bone mass and reducing fracture risk. Likewise, mechanical stimulation can significantly enhance bone apposition and prevent bone loss, but its clinical effects on fracture susceptibility are less certain. Many of the osteogenic effects of iPTH are localized to biomechanically suboptimal bone surfaces, whereas mechanical loading directs new bone formation to high-stress areas and not to strain-neutral areas. These differences in localization in new tissue, resulting from load-induced vs iPTH-induced bone accumulation, should affect the relation between bone mass and bone strength, or “tissue economy.” We investigated the changes in bone mass and strength induced by 6 wks mechanical loading, and compared them to changes induced by 6 wks iPTH treatment. Loading and iPTH both increased ulnar bone accrual, as measured by bone mineral density and content, and fluorochrome-derived bone formation. iPTH induced a significantly greater increase in bone mass than loading, but ulnar bone strength was increased approximately the same amount by both treatments. Mechanical loading during growth can spatially optimize new bone formation to improve structural integrity with a minimal increase in mass, thereby increasing tissue economy i.e., the amount of strength returned per unit bone mass added. Furthermore, exercise studies in which only small changes in bone mass are detected might be more beneficial to bone health and fracture resistance than has commonly been presumed.

McAteer, Maureen E.; Niziolek, Paul J.; Ellis, Shana N.; Alge, Daniel L.; Robling, Alexander G.



Decreased serum concentrations of 1,25(OH) 2-vitamin D 3 in patients with gout  

Microsoft Academic Search

We measured serum concentrations of 1,25(OH)2-vitamin D3, 25(OH)-vitamin D3, parathyroid hormone (PTH), and uric acid in 113 male patients with primary gout and 51 normal male control subjects. Serum 1,25(OH)2-vitamin D3 was significantly lower in patients with gout compared with control subjects (38.4 ± 11.9 v 44.4 ± 11.0 pg\\/mL, P < .005), whereas no differences were observed between the

Sumio Takahashi; Tetsuya Yamamoto; Yuji Moriwaki; Zenta Tsutsumi; Jun-ichi Yamakita; Kazuya Higashino



Parathyroid hormone (PTH) secretion: stimulation of PTH secretion by a peptide derived from the adenosine diphosphate-ribosylation factor.  


Using preparations of dispersed bovine parathyroid cells, we have investigated the effect of a 16-residue synthetic peptide, ARF-16, which corresponds to the N-terminus of the ADP-ribosylation factor, on the secretion of PTH. We find it to be a very effective secretagogue for PTH secretion, acting in a dose- and time-dependent manner. At concentrations in the range of 15-25 microM, the ARF peptide stimulated PTH secretion to a greater degree than low extracellular calcium, and at 25 microM was more effective than isoproterenol. The stimulatory effect of ARF was not dependent on the extracellular calcium concentration over the range of 0.5-3 mM. Upon testing other synthetic peptides of similar size we found no effect on PTH secretion, indicating that the ARF-16 effect is specific. In an attempt to define the structural elements of ARF that are required for activity, we tested several analogs of ARF with amino acids deleted from the N- and C-terminus. Deletion of the 2 N-terminal residues yielded a peptide with substantially reduced activity. Further deletions from the N-terminus yielded an inactive peptide. Similarly, a peptide with deletions of 3 residues from the C-terminus was inactive. Thus, the activity of ARF-16 requires both the N- and C-terminal sequence, suggesting that the 16-residue peptide is the minimal sequence required for full activity. Measurements of cAMP concentrations indicate that the stimulatory effect is not mediated via this second messenger. The ARF peptide does not alter intracellular calcium, suggesting that its effect is not mediated by calcium. Although cells incubated with ARF are vigorously stimulated to secrete PTH, this effect is reversible, as demonstrated by washing cells free of ARF, whereupon PTH secretion returns to basal levels. These results indicate that the peptide is not entering the cells, but is effecting secretion through a low affinity interaction at the cell surface. Other experiments, in which the capacity for ARF stimulation was abolished after a brief exposure of the cells to trypsin, support this conclusion. Characteristics of the ARF stimulatory effect, such as dose dependency and reversibility, lead us to conclude that the peptide is probably acting on the regulated secretory pathway. As the effect is not dependent on extracellular calcium levels and is not mediated via cAMP, we believe that this peptide will be a useful additional tool for future studies of the mechanisms of PTH secretion. PMID:8033805

Newman, L; Drees, B; Forte, L; Hamilton, J



The use of sestamibi imaging in parathyroid hyperplasia.  


The authors describe a 42-year-old man with parathyroid hyperplasia secondary to chronic renal failure. Parathyroidectomy was indicated because of persistent hypercalcemia and an increasing parathyroid hormone level despite medical management. A parathyroid sestamibi scan was performed immediately before operation and a gamma-detecting probe was used during operation. Six parathyroid glands weighing nearly 21 g were present. Without the use of the gamma-detecting probe during operation, one of the glands would have been missed. The efficacy of sestamibi scanning with parathyroid hyperplasia is discussed. PMID:12607864

Fernandez, Kristen L; Turer, Paul; Spiegler, Ethan J; Singer, John A



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

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.