Adaptation of vitamin D metabolism to calcium challenge: is it dependent on parathyroid hormone?

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-dihydroxycholecalciferol [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)D3 <2.5 nmol/l (10 ng/ml)], serum labelled 1,25-(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 in vitamin D-replete individuals, who appeared 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, immuno-reactive parathyroid hormone, calcium or Pi. Production of labelled 24,25-(OH)2D3 was inappropriately high for the prevailing nutritional state. 6. The indirectly estimated molar 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.

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Role of prolactin in vitamin D metabolism and calcium absorption during lactation in the rat

Journal of Endocrinology ◽

10.1677/joe.0.0940443 ◽

1982 ◽

Vol 94 (3) ◽

pp. 443-453 ◽

Cited By ~ 53

Author(s):

C. J. Robinson ◽

E. Spanos ◽

M. F. James ◽

J. W. Pike ◽

M. R. Haussler ◽

...

Keyword(s):

Vitamin D ◽

Alkaline Phosphatase ◽

Parathyroid Hormone ◽

Alkaline Phosphatase Activity ◽

Plasma Levels ◽

Calcium Absorption ◽

High Plasma ◽

Intestinal Calcium Absorption ◽

Vitamin D Metabolism

Intestinal calcium absorption and plasma levels of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) were measured in lactating and non-lactating rats and the effects of bromocriptine and exogenous prolactin treatment were evaluated. In lactating rats calcium absorption and plasma levels of parathyroid hormone, 1,25(OH)2D3 and alkaline phosphatase activity were significantly increased. Bromocriptine treatment significantly reduced the enhanced calcium absorption and levels of plasma 1,25(OH)2D3 and alkaline phosphatase but had no significant effect on plasma levels of parathyroid hormone. Prolactin administered with bromocriptine to lactating animals prevented all the changes observed with bromocriptine treatment alone. It was concluded that the increased plasma levels of prolactin during lactation lead to high plasma levels of 1,25(OH)2D3 which are responsible for the enhanced intestinal calcium absorption.

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Acute Effects of Parathyroid Hormone on Vitamin D Metabolism in Patients with the Bone Loss of Aging

Obstetrical & Gynecological Survey ◽

10.1097/00006254-198303000-00017 ◽

1983 ◽

Vol 38 (3) ◽

pp. 165-167

Author(s):

O. HELMER SØRENSEN ◽

B O LUMHOLTZ ◽

BIRGER LUND ◽

BJARNE LUND ◽

INGE L. HJELMSTRAND ◽

...

Keyword(s):

Vitamin D ◽

Parathyroid Hormone ◽

Bone Loss ◽

Acute Effects ◽

Vitamin D Metabolism

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Pathophysiology of chronic kidney disease-mineral and bone disorder

10.1093/med/9780199592548.003.0117 ◽

2015 ◽

Author(s):

Alexandra Voinescu ◽

Nadia Wasi Iqbal ◽

Kevin J. Martin

Keyword(s):

Chronic Kidney Disease ◽

Vitamin D ◽

Parathyroid Hormone ◽

Kidney Disease ◽

Fibroblast Growth Factor 23 ◽

Serum Levels ◽

Mineral And Bone Disorder ◽

Vitamin D Metabolism ◽

Bone Disorder ◽

Calcium Phosphorus

Chronic kidney disease is associated with the inability to control normal mineral homeostasis, resulting in abnormalities in serum levels of calcium, phosphorus, parathyroid hormone, fibroblast growth factor 23 (FGF23) and vitamin D metabolism. These disturbances lead to the development of secondary hyperparathyroidism, skeletal abnormalities, vascular calcifications, and other systemic manifestations. Traditionally, mineral and bone abnormalities seen in chronic kidney disease were included in the term ‘renal osteodystrophy’. More recently, the term chronic kidney disease-mineral and bone disorder was introduced to define the biochemical abnormalities of phosphorus, parathyroid hormone, FGF23, calcium, or vitamin D metabolism, abnormalities in bone remodelling and mineralization, and vascular or other soft tissue calcifications.

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Effects of parathyroid hormone rhPTH(1–84) on phosphate homeostasis and vitamin D metabolism in hypoparathyroidism: REPLACE phase 3 study

Endocrine ◽

10.1007/s12020-016-1141-0 ◽

2016 ◽

Vol 55 (1) ◽

pp. 273-282 ◽

Cited By ~ 19

Author(s):

Bart L. Clarke ◽

Tamara J. Vokes ◽

John P. Bilezikian ◽

Dolores M. Shoback ◽

Hjalmar Lagast ◽

...

Keyword(s):

Vitamin D ◽

Parathyroid Hormone ◽

Phosphate Homeostasis ◽

Phase 3 ◽

Vitamin D Metabolism

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The Lack of Effect of Chronic Metabolic Acidosis on 25-OH-Vitamin D Metabolism and Serum Parathyroid Hormone in Humans*†

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem-43-5-1047 ◽

1976 ◽

Vol 43 (5) ◽

pp. 1047-1055 ◽

Cited By ~ 74

Author(s):

HUGO P. WEBER ◽

RICHARD W. GRAY ◽

JESUS H. DOMINGUEZ ◽

JACOB LEMANN

Keyword(s):

Vitamin D ◽

Parathyroid Hormone ◽

Metabolic Acidosis ◽

Serum Parathyroid Hormone ◽

Vitamin D Metabolism ◽

Chronic Metabolic Acidosis ◽

25 Oh Vitamin D

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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

Journal of Endocrinology ◽

10.1677/joe.0.1710249 ◽

2001 ◽

Vol 171 (2) ◽

pp. 249-257 ◽

Cited By ~ 13

Author(s):

T Michigami ◽

H Yamato ◽

H Suzuki ◽

Y Nagai-Itagaki ◽

K Sato ◽

...

Keyword(s):

Vitamin D ◽

Parathyroid Hormone ◽

Related Protein ◽

Humoral Hypercalcemia Of Malignancy ◽

Vitamin D Metabolism ◽

Hydroxyvitamin D ◽

Humoral Hypercalcemia ◽

Parathyroid Hormone Related Protein ◽

Severe Hypercalcemia ◽

25 Hydroxyvitamin D

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.

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