The effect of 1,25 dihydroxycholecalciferol on parathyroid hormone secretion by monolayer cultures of bovine parathyroid cells

Chan, Yuk–Luen; McKay, Catriona; Dye, Evelyn S.; Slatopolsky, Eduardo

doi:10.1007/bf02556591

Cited by 109 publications

(30 citation statements)

References 29 publications

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“…An alternative explanation for the increase in PTH with age might stem from findings that altered vitamin D metabolism could modulate iPTH levels. It was reported that parathyroid cells exposed to 1,25-dihydroxycholecalciferol had a significantly decreased rate of PTH secretion due to declines in the steady state level of prepro-PTH mRNA and the rate of PTH gene transcription (60)(61)(62). Decreased suppression would be consistent with previous findings of a lower concentration of the vitamin D metabolite in aged rats (63) and a decreased renal 1-a hydroxylase activity in mitochondria from the 24 mo animal (64).…”

Section: Discussionsupporting

confidence: 85%

Desensitization to parathyroid hormone in renal cells from aged rats is associated with alterations in G-protein activity.

Hanai

Liang²,

Cheng³

et al. 1989

J. Clin. Invest.

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Parathyroid hormone (PTH)-stimulated Na+/Ca2" exchange activity, but not forskolin-sensitive Na'-dependent Ca2+ efflux, was blunted in renal cortical cells from aged rats. PTH-sensitive adenylate cyclase activity in renal membranes from senescent rats also declined, but forskolin-stimulated activity did not change. In addition, cholera toxin-and pertussis toxin-stimulated Na'-dependent Ca2" efflux and cAMP formation were blunted in cells from aged animals. Further, cells from aged rats had decreased G5-a and G1-a proteins, as detected by ADP-ribosylation. These findings would be consistent with the proposal of an age-associated heterologous desensitization that involved the G-proteins. Serum concentrations of iPTH were increased in the old rat, suggesting that the desensitization to PTH in the aging rat represented an adaptive response to prolonged stimulation by the hormone. This hypothesis was supported by the findings that the attenuated PTH-sensitive Na+/ Ca2" exchange activity, cAMP formation, and adenylate cyclase activity in cells from old rats could be reversed by parathyroidectomy. The decreased label in cholera toxin-catalyzed ADP-ribosylated G.-a and pertussis toxin catalyzed ADP-ribosylated Gj-a found in cells from aged rats was also largely negated by the surgery. In conclusion, the results suggest that the age-related blunting in the responses of renal cells to PTH was associated with a deficit in G-protein function and that this alteration could be reversed by removal of the parathyroid gland.

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Section: Discussionsupporting

confidence: 85%

Desensitization to parathyroid hormone in renal cells from aged rats is associated with alterations in G-protein activity.

Hanai

Liang²,

Cheng³

et al. 1989

J. Clin. Invest.

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“…According to the results shown in Fig. 1 Several studies suggest that 1 ,25(OH)2D3 directly inhibits the secretion of PTHfrom the parathyroid glands (22)(23)(24)(25) and also suppresses the production of PTHmRNA in parathyroid glands, independent of the concentration of ionized Ca (26)(27)(28). In the present study, the weekly administration of 8.0 |Ug of 1,25(OH)2D3 suppressed the PTH level without elevating the serum Ca.…”

Section: Discussionsupporting

confidence: 64%

Suppression of Secondary Hyperparathyroidism in Chronic Dialysis Patients by Single Oral Weekly Dose of 1,25-Dihydroxycholecalciferol.

et al. 1993

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Eleven hemodialysis patients who developed refractory secondary hyperparathyroidism, despite conventional vitamin D therapy, were treated with large oral doses of 1,25-dihydroxycholecalciferol [1,25(OH)2D3]. Therapeutic regimen was a single oral dose of up to 8.0 jug administered once weekly following hemodialysis. A maximum serum level of 1,25(OH)2D occurred four hours after the 8.0 jig dose. A positive correlation (Y=84.3X-22.1: P<0.01) was found between the maximal serum 1,25(OH)2D concentration (Cmax) and the dose of 1,25(OH)2D3 when plotted on a logarithmic scale. Forty-eight hours after the administration of the 8.0 jag dose, the parathyroid hormone (PTH) level and the alkaline phosphatase activity (ALP) were markedly decreased without evidence of hypercalcemia. A significant inverse relationship was found between the Cmax of 1,25(OH)2D and the percent change in the PTH level measured after 48 hours, either with carboxy-terminal (C-PTH) or the highly sensitive mid-portion assay (HS-PTH). From these results, the level of serum 1,25(OH)2D required to blunt the rise in serum PTH was 168 pg/ml and 203 pg/ml, respectively; these serum levels were achieved by the oral administration of doses of 6.0-8.0 |LLg or higher. There were no adverse effects of treatment. Following this study, one patient was continuously treated with 8.0 jig of 1,25(OH)2D3 orally once a week for 18 months. There was a therapeutic effect (as evidenced by PTHsuppression, ALPsuppression and the disappearance of subjective complaints) without the development of severe hypercalcemia or hyperphosphatemia. This treatment may help to prevent or treat secondary hyperparathyroidism in patients receiving long-term dialysis.

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“…[Ca ion ] may fall because increased phosphate will decrease the physicochemical driving forces for bone mineral dissolution (21) and favor ectopic precipitation of Ca phosphate complexes (90). In addition, phosphate retention will directly decrease serum 1,25(OH) 2 (99,(102)(103)(104)(105). In addition, during renal failure, there is decreased binding of 1,25(OH) 2 D 3 to the parathyroid cells (106).…”

Section: Ckd In Patients Who Are Not On Dialysismentioning

confidence: 99%

Contribution of Intestine, Bone, Kidney, and Dialysis to Extracellular Fluid Calcium Content

Bushinsky

2010

Clinical Journal of the American Society of Nephrology

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Calcium (Ca) balance is the net of Ca intake and output from the body over a period of time. The concept of Ca balance does not consider the redistribution of Ca that often occurs in patients with chronic kidney disease (CKD), especially those who are on dialysis, which is often in the form of soft tissue and/or vascular calcification. In this article, we consider movement of Ca with respect to the extracellular fluid (ECF) and develop a mathematical formulation for Ca homeostasis with respect to the ECF that includes input and output from the diet, the bone, the kidney, and dialysis. We consider calcium homeostasis in healthy individuals and in patients with excess parathyroid hormone, excess 1,25-dihydroxyvitamin D 3 , and metabolic acidosis; patients who have CKD and are not on dialysis; and, finally, patients who have CKD and are on dialysis. On the basis of a number of assumptions, dialysis patients with a daily intake of >37.5 mmol of elemental Ca (1.5 g) have movement of Ca into the ECF even without supplemental activated vitamin D. Addition of activated vitamin D, which increases intestinal Ca absorption and can increase resorption of Ca from bone, leads to the movement of Ca into the ECF at virtually all levels of intake; however, there are numerous unanswered questions regarding Ca homeostasis in patients with CKD, including how much of the Ca, administered as a phosphate binder, is absorbed and what is the fate of this absorbed Ca. Until these pressing questions are answered with well-designed experiments, we do not know whether we are doing more harm than good for our dialysis patients by administering additional Ca as a phosphate binder, especially when they also receive activated vitamin D.

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The effect of 1,25 dihydroxycholecalciferol on parathyroid hormone secretion by monolayer cultures of bovine parathyroid cells

Cited by 109 publications

References 29 publications

Desensitization to parathyroid hormone in renal cells from aged rats is associated with alterations in G-protein activity.

Desensitization to parathyroid hormone in renal cells from aged rats is associated with alterations in G-protein activity.

Suppression of Secondary Hyperparathyroidism in Chronic Dialysis Patients by Single Oral Weekly Dose of 1,25-Dihydroxycholecalciferol.

Contribution of Intestine, Bone, Kidney, and Dialysis to Extracellular Fluid Calcium Content

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