THE EFFECT OF CALCIUM AND DIBUTYRYL-cAMP ON THE SECRETION OF PARATHYROID HORMONE BY HUMAN PARATHYROID ADENOMAS IN ORGAN CULTURE

1977 ◽  
Vol 85 (3) ◽  
pp. 541-547 ◽  
Author(s):  
M. Dietel ◽  
G. Dorn ◽  
R. Montz ◽  
E. Altenähr

ABSTRACT The effect of different calcium concentrations as well as dibutyryl-cyclic adenosine 3′,5′-monophosphate (DB-cAMP) on the secretion of parathyroid hormone by human parathyroid adenomas taken from patients with primary hyperparathyroidism (pHPT) was studied in organ culture. Their influence on the release of hormone was determined. The tissue was incubated in culture medium for 4 h; the medium was changed hourly and analyzed for immunoreactive parathyroid hormone (PTH) by radioimmunoassay. The hormone secretion showed an inverse relationship to different calcium concentrations in the medium and could be stimulated independently of the calcium concentration by adding DB-cAMP. These results suggest that the examined parathyroid adenomas are sensitive to physiological stimuli.

1974 ◽  
Vol 75 (2) ◽  
pp. 286-296 ◽  
Author(s):  
J. H. Lockefeer ◽  
W. H. L. Hackeng ◽  
J. C. Birkenhäger

ABSTRACT In 22 of 28 cases of primary hyperparathyroidism (PHP) the rise in the serum immunoreactive parathyroid hormone (IRPTH or PTH) level observed in response to lowering of the serum calcium by EDTA, exceeded that obtained in 8 control subjects. In 5 of these 22 patients who were studied again after parathyroidectomy the supranormal response was abolished. Fifteen of these 22 hyper-responsive PHP patients had basal IRPTH levels not exceeding the highest level in the controls and that of other groups of patients investigated (idiopathic hypercalciuria, non-parathyroid hypercalcaemia, operated PHP). Fourteen of the 22 hyper-reactive patients with PHP did not show hypocalcaemia during the infusion of EDTA. The extent of the release of PTH elicited by EDTA in cases of PHP does not as yet allow a prediction of the amount of pathological parathyroid tissue present, although all the PHP patients showing a normal release of PTH had a relatively small mass of parathyroid tissue (up to about 1 g) subsequently removed. In 9 cases of nephrolithiasis (8 of whom had idiopathic hypercalciuria) and in 7 cases of non-parathyroid hypercalcaemia, a normal PTH release was found.


1977 ◽  
Vol 86 (3) ◽  
pp. 533-538 ◽  
Author(s):  
E. Altenähr ◽  
M. Dietel ◽  
G. Dorn ◽  
R. Montz

ABSTRACT The effect of 1,25-dihydroxycholecalciferol (1,25-(OH)2-D3) on parathyroid hormone secretion by porcine parathyroid glands and human parathyroid adenoma tissue was investigated by in vitro incubation. The addition of 100 nmoles 1,25-(OH)2-D3 to the medium inhibited significantly the release of immunoreactive parathyroid hormone by 63–65 %. This suppression was reversible when 1.25-(OH)2-D3 was removed again. The inhibition of parathyroid hormone release observed in human parathyroid adenoma tissue was similar to that in normal porcine parathyroid glands. This indicates that adenoma tissue is sensitive to regulatory influences. As well as calcium, 1,25-(OH)2-D3 may act as another feedback inhibitor of parathyroid hormone secretion.


1978 ◽  
Vol 88 (3) ◽  
pp. 528-534 ◽  
Author(s):  
C. Christiansen ◽  
P. C. Baastrup ◽  
P. Lindgreen ◽  
I. Transbøl

ABSTRACT Ninety-six manic-depressive patients were studied during long-term lithium treatment. Highly significant elevations were observed respecting the levels of serum immunoreactive parathyroid hormone (P < 0.001) as well as the protein-corrected levels of serum calcium (P < 0.001) and serum magnesium (P <0.001), thus indicating a state of 'primary' hyperparathyroidism. The patients as a group had normophosphataemia and normophosphatasia supporting the impression of a rather mild state of biochemical hyperparathyroidism.


1991 ◽  
Vol 260 (2) ◽  
pp. E220-E225 ◽  
Author(s):  
J. Fox

Plasma immunoreactive parathyroid hormone (irPTH) levels increase with aging. This study determined 1) whether NH2-terminal irPTH secretory responses to induced hypocalcemia differ between adult (6-mo-old) and aged (24- to 26-mo-old) male rats and 2) whether a higher set point for irPTH release by Ca is responsible for the elevated irPTH levels with aging. Basal irPTH levels were 68% higher and 1,25-dihydroxyvitamin D3 levels were 44% lower in aged rats. An acutely induced, constant hypocalcemic stimulus [0.32 mM decrement in ionized Ca (Ca2+) for 2 h] was developed in catheterized conscious adult and aged rats by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) infusion using the Ca clamp technique. The initial irPTH secretory response to acute hypocalcemia (5-10 min) was reduced in aged rats (1.9- vs. 3.1-fold increase), suggesting reduced hormone stores. However, higher sustained irPTH levels (30 min to 2 h) were maintained in aged rats, indicating increased irPTH synthesis and release. The EGTA infusion rate necessary to maintain constant hypocalcemia was less in aged rats, suggesting skeletal resistance to PTH. Slow EGTA and Ca infusions were used to determine irPTH secretion at plasma Ca2+ levels from 0.7 to 1.5 mM. In aged rats, irPTH levels were higher at all Ca2+ concentrations, but the set point for irPTH release by Ca2+ was the same as in adult rats. Thus the elevated irPTH secretion in aged rats is not caused by a change in the set point for irPTH release but does result in decreased irPTH stores.


2013 ◽  
Vol 29 (2) ◽  
pp. 282-289 ◽  
Author(s):  
M. E. Rodriguez-Ortiz ◽  
A. Canalejo ◽  
C. Herencia ◽  
J. M. Martinez-Moreno ◽  
A. Peralta-Ramirez ◽  
...  

2005 ◽  
Vol 153 (4) ◽  
pp. 587-594 ◽  
Author(s):  
Takehisa Kawata ◽  
Yasuo Imanishi ◽  
Keisuke Kobayashi ◽  
Takao Kenko ◽  
Michihito Wada ◽  
...  

Cinacalcet HCl, an allosteric modulator of the calcium-sensing receptor (CaR), has recently been approved for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis, due to its suppressive effect on parathyroid hormone (PTH) secretion. Although cinacalcet’s effects in patients with primary and secondary hyperparathyroidism have been reported, the crucial relationship between the effect of calcimimetics and CaR expression on the parathyroid glands requires better understanding. To investigate its suppressive effect on PTH secretion in primary hyperparathyroidism, in which hypercalcemia may already have stimulated considerable CaR activity, we investigated the effect of cinacalcet HCl on PTH-cyclin D1 transgenic mice (PC2 mice), a model of primary hyperparathyroidism with hypo-expression of CaR on their parathyroid glands. A single administration of 30 mg/kg body weight (BW) of cinacalcet HCl significantly suppressed serum calcium (Ca) levels 2 h after administration in 65- to 85-week-old PC2 mice with chronic biochemical hyperparathyroidism. The percentage reduction in serum PTH was significantly correlated with CaR hypo-expression in the parathyroid glands. In older PC2 mice (93–99 weeks old) with advanced hyperparathyroidism, serum Ca and PTH levels were not suppressed by 30 mg cinacalcet HCl/kg. However, serum Ca and PTH levels were significantly suppressed by 100 mg/kg of cinacalcet HCl, suggesting that higher doses of this compound could overcome severe hyperparathyroidism. To conclude, cinacalcet HCl demonstrated potency in a murine model of primary hyperparathyroidism in spite of any presumed endogenous CaR activation by hypercalcemia and hypo-expression of CaR in the parathyroid glands.


1986 ◽  
Vol 6 (12) ◽  
pp. 1057-1063 ◽  
Author(s):  
Peter Nygren

Monolayer culture of bovine parathyroid cells for 24 hours resulted in a right-shift of the dose-effect relationships for Ca2+-inhibition of parathyroid hormone (PTH) release and the dependence of the cytoplasmic Ca2+ concentration (Ca2+) on extracellular Ca2+ as well as in a less suppressible hormone release. After 4 days of culture, hormone secretion was almost non-suppressible and Cai2+ increased poorly in response to a rise in extracelluiar Ca2+. Ionomycin, a Ca2+ ionophore, raised Cai2+, but there was only a small inhibition of PTH release and the correlation between Cai2+ and secretion was weak. A deteriorated Cai2+ regulation and a decreased inhibitory action of cytoplasmic Ca2+ on PTH release were also found in ceils from human parathyroid adenomas. Functional dedifferentiation of the parathyroid cell thus results from both defective regulation and action of cytoplasmic Ca2+.


1992 ◽  
Vol 37 (6) ◽  
pp. 565-569
Author(s):  
Pinhas P. Schachter ◽  
Mark D. Christy ◽  
Itamar S. Avigad ◽  
Moshe Shabtay ◽  
George S. Leight

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