Parathormone
Hormones

Author: Gianpiero Pescarmona
Date: 12/08/2007

Description

PTH and Gastrin

Evaluation of serum parathyroid hormone-related peptide in hyperthyroid patients, 2010

Abstract

Background Hypercalcemia occurs in 10–20% of patients with hyperthyroidism, but its pathogenesis is still unclear.

Aim To evaluate changes in parathyroid hormone-related peptide (PTH-rP) concentration in hyperthyroid patients compared with healthy controls.

Methods We studied PTH-rP, parathormone (PTH) and ionized calcium levels in 153 hyperthyroid patients, and 89 control subjects. These variables were revaluated after attainment of euthyroidism with the antithyroid drug carbimazole for 6 months in a subgroup of 47 patients.

Results Pretreatment PTH-rP and ionized calcium level were significantly higher in hyperthyroid patients than in controls, whereas an opposite trend occurred for PTH. All parameters normalized after carbimazole therapy.

Conclusion Untreated hyperthyroid patients exhibited a significant elevation in serum ionized calcium and PTH-rP and a significant reduction in serum PTH levels when compared with healthy controls. Our data favoured the hypothesis of a direct involvement of PTH-rP in the pathogenesis of hypercalcemia in hyperthyroid patients.

The cells of the parathyroid glands have surface G-protein-coupled receptors that bind Ca2+ (the same type of receptor is found on the calcitonin-secreting cells of the thyroid and on the calcium absorbing cells of the kidneys). Binding of Ca2+ to this receptor depresses the secretion of PTH and thus leads to a lowering of the concentration of Ca2+ in the blood. Two classes of inherited disorders involving mutant genes encoding the Ca2+ receptor occur:

defective PTH release can be asssociated to insuline defective release?

Calcium and phosphorus metabolism disturbances after renal transplantation.

Serum parathyroid hormone concentrations in senile dementia (Alzheimer's disease).
Shore D, Wills MR, Savory J, Wyatt RJ.

The accumulation of aluminum in the cerebral cortex has been implicated as a factor in the pathogenesis of Alzheimer type senile dementia (SD) and in the dialysis dementia found in patients with chronic renal failure on long-term intermittent hemodialysis treatment. In animal studies, parathyroid hormone (PTH) produces increased absorption of aluminum from the gastrointestinal tract and elevations of aluminum in the cerebral cortex. It has been proposed that PTH elevations may increase tissue aluminum loads in patients with senile dementia. The present study was undertaken to investigate the status of circulating PTH in patients with SD and age/sex matched controls. No significant differences were found between these groups. Elevated PTH (when it did occur) seemed to be related to the degree of renal impairment rather than dementia. Differences in the distribution of aluminum in patients with dialysis dementia and SD are discussed.

High prevalence of vitamin D deficiency and reduced bone mass in elderly women with Alzheimer's disease. 1998

Biosynthesis and function of all-trans- and 9-cis-retinoic acid in parathyroid cells. 1996

Chicken parathyroid hormone gene expression in response to gastrin, omeprazole, ergocalciferol, and restricted food intake, 1997

  • Abstract
    Treatment with omeprazole, a long-acting proton pump inhibitor of acid secretion, induces hypergastrinemia. In chickens, omeprazole induces growth not only of the acid-producing mucosa (probably reflecting the trophic action of gastrin), but also of the parathyroid glands (hypertrophy + hyperplasia), while suppressing bone density and body weight gain without affecting blood calcium. The first part of the present study was concerned with the effect of omeprazole, ergocalciferol (vitamin D2), and restricted food intake on the gene expression of parathyroid hormone (PTH) in the parathyroid glands of the chicken. Chickens were treated with omeprazole (400 micromol/kg/day, I.M.), food restriction, omeprazole + food restriction, ergocalciferol (250 000 IU/kg/day, S.C.), or ergocalciferol + omeprazole for 5 weeks. The weight gain of the chickens was monitored, and the weights of the parathyroid glands and femurs were determined at sacrifice. PTH mRNA in the parathyroid glands was analyzed by Northern blot. The second part of the study examined the effect of 3 weeks of continuous gastrin infusion (chicken gastrin 20-36, 5 nmol/kg/hour, S.C.) on the expression of PTH mRNA in the parathyroid glands. Omeprazole reduced the body weight and femur density (ash weight per volume) while greatly increasing the weight of the parathyroid glands and the PTH gene expression. Food restriction alone and ergocalciferol alone (at a dose that raised blood Ca2+) were without effect, but food restriction greatly enhanced the omeprazole-evoked increase in parathyroid gland weight and PTH gene expression. Gastrin increased the weight of the parathyroid glands and reproduced the effect of omeprazole on PTH gene expression. Hence, it seems likely that the effect of omeprazole reflects the ensuing hypergastrinemia.

Parathyroid Disease - Yale School of Medicine

Drugs increasing PTH release

Endocrine functions of bone in mineral metabolism regulation 2008
fulltext

PTH targets

Regulation of the PT cell Na+-Pi cotransporter Npt2a by PTH

Changes in plasma electrolytes during acclimatization at high altitude. 1996
Khan DA, Aslam M, Khan ZU.
J Pak Med Assoc. 1996 Jun;46(6):128-31.

The effects on plasma electrolytes and related hormones were determined in non-acclimatized low lander males, exposed for 96 hours to an altitude of 4424 meters. Twenty healthy soldiers aged 18-34 years travelled by road from an altitude of 2303 meters to 4424 meters over a period of 10 hours. Plasma sodium levels (142.09 +/- 1.14 mmol/1) and aldosterone (16.61 +/- 5.70 ng/ml) decreased to 139.69 mmol/1 and 11.6 +/- 4.60 ug/ml respectively after 96 hours of acute exposure to high altitude (p < 0.05). The plasma potassium and chloride levels did not show significant change, while, plasma HCO3 decreased gradually from 21.06 +/- 1.38 mmol/1 to 18.55 +/- 0.82 mmol/1 after 96 hours exposure to this altitude (p < 0.01). The plasma ionized calcium and plasma phosphate concentration decreased from 1.32 +/- 0.11 mmol/1 and 1.58 +/- 1.3 mmol/1 to 1.20 +/- 0.05 mmol/1 and 1.47 +/- 0.99 mmol/1 respectively (p < 0.05). Plasma parathyroid hormone (PTH) level increased from 4.54 +/- 2.1 ng/ml to 11.19 +/- 4.31 ng/ml after 48 hours with subsequent decline to 2.52 +/- 1.7 ng/ml after 96 hours exposure to high altitude. It may be concluded that the process of acclimatization to sudden exposure to high altitude is characterised by fall in plasma aldosterone and PTH with subsequent decrease of related electrolytes.

PTH and fgf-23 overexpression

PTH receptors

Identification of a retinoic acid-inducible element in the murine PTH/PTHrP (parathyroid hormone/parathyroid hormone-related peptide) receptor gene. 1999

PTH retinoic

PTH and atrial fibrillation

cAMP+and+atrial+fibrillation

PTH and PSA

pth+and+psa

Comments
2010-02-21T23:47:20 - Paolo Pescarmona

Potential Role of Parathyroid Hormone (PTH) in Fracture Repair

Stimulation of Fracture-Healing with Systemic Intermittent Parathyroid Hormone Treatment 2008

PTH is a major systemic regulator of the concentrations of calcium, phosphate, and active vitamin-D metabolites in blood and cellular activity in bone. PTH is naturally produced as an 84 amino-acid peptide. However, it has been determined that the N-terminal fragment, PTH 1-34 (teriparatide), can reproduce the major biological actions attributed to full-length PTH, including activation of adenylyl cyclase in bone and kidney cells, increased urinary excretion of cyclic adenosine monophosphate and phosphate in rats, and elevation of blood calcium in rats, dogs. Intermittently administered PTH and amino-terminal PTH peptide fragments or analogs also augment bone mass and currently are being introduced into clinical practice as therapies for osteoporosis.
There are two primary areas of PTH research with regard to fractures — fracture prevention and the use of PTH to enhance bone repair after fracture.
In a study, 270 male rats underwent standard closed femoral fractures, were divided into three groups that were administered daily subcutaneous injections of 5 mg/kg or 30 mg/kg of PTH (1-34) or vehicle (saline solution). Fractured bones were harvested twenty-one, thirty-five, or eighty-four days after fracture and analyzed with use of microquantitative computed tomography and mechanical testing (Enhancement of Experimental Fracture-Healing by Systemic Administration of Recombinant Human Parathyroid Hormone (PTH 1-34) 2005)

Fig. 1

Representative microquantitative computed tomographic images of fracture calluses from the three experimental groups on days 21, 35, and 84 after fracture. Radiodensity is increased in both the 5-mg/kg and the 30-mg/kg groups at each of the three time-points.
Older animals would respond to PTH as robustly as younger animals?
PTH treatment of healing fractures in these older rats led to both increased callus formation and increased mechanical strength by twenty-one days after fracture. The primary difference noted between fracture repair in old and young control rats was the rate at which maximum callus volume was achieved. Younger rats reached maximum callus volume by twenty days after fracture, while older control rats had little callus volume at twenty-one days and continued to accrue callus volume until finally peaking at fifty-six days after fracture. In contrast, both old and young PTH-treated animals had achieved maximum callus volumes by day 21 after fracture, demonstrating that PTH was able to enhance the rate of callus formation in older rats. PTH treatment also enhanced the ultimate load of the fractures by 160% at twenty-one days of healing and by 270% at fifty-six days in comparison with controls. These results demonstrate that PTH treatment can increase the rate of callus formation and restore bone strength even in older animals with diminished callus formation.
Cellular Mechanisms of PTH Action
The current consensus in this area is that PTH treatment increases bone mineral density and reduces fracture risk through the induction of an overall increase in coupled remodelling.
Several studies have noted that both osteoclas mediated bone resorption and osteoblast-mediated new bone formation are enhanced in response to intermittent PTH treatment. One crucial observation consistent among all of the fracture studies on PTH, is the increased callus volume.
PTH preferentially enhances chondrocyte recruitment and the rate of chondrocyte maturation in the fracture callus of mice. Both high-resolution radiographs (Faxitron X-Ray, Wheeling, Illinois) and microquantitative computed tomographic imaging demonstrate that PTH-treated fractures generate larger total callus volumes in this murine closed femoral fracture model (Fig. 2)

Fig. 2

A: Faxitron high-resolution radiographic images showing vehicle-treated versus PTH (1-34)-treated fractures at fourteen and twenty-one days after fracture.
B: Histological images of vehicle-treated versus PTH (1-34)-treated fractures at five and ten days after fracture (original magnification, •4). All sections were stained with safranin-O and fast green, which stains chondrogenic cells red. Note the increased cartilage volume at day 5 and day 10.
C through F: Graphic presentations of selected quantitative data from the microquantitative computed tomographic analysis of
fracture-healing. The results of a two-factor analysis of variance with a Tukey post hoc assessment are given on each plot. (If no differences were found, then there are no letter annotations or footnotes.)
C: Total callus volume, effect of treatment (p = 0.0016) and time (day 14 > day 28, p = 0.0043).
D: Callus length a not equal to b, effect of treatment (p = 0. 0001).
E: Bone volume, effect of treatment (p = 0.0318) and time (day 14, day 21 > day 10, p = 0.0001).
F: Average mineral density; groups not connected by the same horizontal line are significantly different. Effect over time (day 28 > day 21 > day 14 > day 10, p < 0.0001). Each group contains n = 5 bones. (Enhanced chondrogenesis and Wnt-signaling in parathyroid hormone treated fractures. J Bone Miner Res., published online August 6, 2007; doi10.1359/JBMR.070724.)

The actions of PTH and PTHrP are mediated by a G protein coupled receptor, referred to as PTH receptor 1 (PTHR1). Ligand binding to PTHR1 stimulates Gαs-mediated activation of adenylyl cyclase which stimulates cAMP production, and subsequent activation of protein kinase (PKA). PTHR1 also stimulates Gαq-mediated activation of protein kinase C (PKC). In addition, PTH activates β-arrestin-mediated activation of extracellular regulated kinase (ERK) signaling. β-arrestin A is also involved in desensitization of cAMP signaling by PTHR1 (Distinct β-Arrestin- and G Protein-dependent Pathways for Parathyroid Hormone Receptor-stimulated ERK1/2 Activation 2006).
In vitro and in vivo evidence indicates that transient activation of the PTHR1 activates multiple interconnected pathways leading to increased survival signaling, decreased replication of osteoblast progenitors, increased differentiation, and the production and/or activation of osteogenic growth factors. The result of these actions is an increase in osteoblast number beyond that needed to refill the resorption cavity created by osteoclasts. The relative importance of prodifferentiating and pro-survival pathways to the ability of intermittent PTH to increase osteoblast number remains to be determined, as does the potential contribution of pro-survival signaling in osteoblast progenitors, in both animals and humans.
All current research clearly demonstrates that systemic PTH treatment can enhance both endochondral and intramembranous bone repair. The published studies demonstrate that systemic PTH treatment leads to increased callus volumes, rates of new bone formation, and restoration of mechanical competence in models of both normal and impaired fracture repair. These studies also show that PTH affects both chondrogenic and osteogenic events during bone repair, suggesting that PTH treatment may be effective in a number of different defect sites and fracture types.

Zmau Isabela

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