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Biomedical subjects

R W Gray

Publications and source records attributed to R W Gray.

16 recordsLinked to original sources

The calciuria of increased fixed acid production in humans: evidence against a role for parathyroid hormone and 1,25(OH)2-vitamin D.

We measured mineral and acid balances, serum iPTH, urinary cAMP/creatinine, and plasma concentrations of 25OHD and 1,25(OH)2D in 7 healthy adults during control conditions and during increased fixed acid production achieved either by the administration of NH4Cl (N = 3) or by increased dietary protein intake (N = 4). When acid production was increased, the subjects were in positive acid balance and negative Ca balance because of increased urinary Ca excretion. Serum iPTH fell slightly but urinary cAMP and the plasma levels of vitamin D metabolites did not change. W conclude that the accelerated skeletal and urinary losses of Ca that occur when fixed acid production is increased are not contributed to nor compensated for by the parathyroid-vitamin D endocrine systems.

Acids

Plasma 1,25-(OH)2-vitamin D concentrations and net intestinal calcium, phosphate, and magnesium absorption in humans.

We evaluated the relationship between plasma concentrations of the renal hormone 1,25-(OH)2-vitamin D and net intestinal absorption of Ca, PO4, and Mg in vitamin D-replete patients eating similar diets, who had undetectable, normal or elevated plasma 1,25-(OH)2-D levels, Net intestinal Ca absorption was positively correlated to plasma 1,25-(OH)2-D concentrations: percentage dietary Ca absorbed = 10 + 0.17 x plasma total 1,25-(OH)2-3, pmole/liter, r = + 0.58; P less than 0.001. By contrast, there was no significant correlation between PO4 or Mg absorption and plasma 1,25-(OH)2-D concentrations. Moreover, significant quantities of PO4 and Mg were absorbed in the absence of detectable plasma 1,25-(OH)2-D. We conclude that net intestinal Ca absorption is critically dependent upon the availability of the renal hormone 1,25-(OH)2-D in vitamin D-replete humans when dietary Ca intake is normal. By contrast, other factors must play a dominant role in regulating net intestinal PO4 and Mg absorption.

Adult

The interrelationships among prolactin, 1,25-dihydroxyvitamin D, and parathyroid hormone in humans.

Serum PRL, parathyroid hormone (PTH), and plasma 1,25-dihydroxyvitamin D [1,25(OH)2D]concentrations were measured in 6 women and 2 men with hyperprolactinemia, 6 normal men and 7 normal women, 4 men and 4 women with primary hyperparathyroidism, and 16 men and 4 women with Ca nephrolithiasis. Plasma 1,25(OH)2D and serum parathyroid hormone (PTH) concentrations were normal in the women and men with hyperprolactinemia. In patients with primary hyperparathyroidism and elevated serum PTH, plasma 1,25(OH)2D concentrations were elevated but serum PRL levels were normal. Likewise, serum PRL levels were normal in patients with Ca nephrolithiasis who had significantly elevated plasma, 1,25(OH)2D concentrations and normal serum PTH concentrations. Thus, hyperprolactinemia due to pituitary adenoma or idiopathic hypersecretion is not accompanied but elevated plasma concentrations of 1,25(OH)2D.

Adenoma

The effects of dihydrotachysterol therapy on the measurement of plasma 1,25-(OH)2-vitamin D in humans.

Anephric patients have undetectable plasma concentrations of 1,25-(OH)2-D, but when anephric patients are treated with DHT2 (Hytakerol), their plasma contains a substance that is co-purified with and displaces authentic 3H-1,25(OH)2-D3 from its intestinal cytoplasmic receptor. The concentration of this substance in the plasma of anephric patients taking DHT2 is proportional to the administered daily dose of DHT2 per kilogram body weight. When DHT2 therapy is discontinued, the substance disappears from plasma with an average t 1/2 of about 8 days.

Dihydrotachysterol

Metabolism and excretion of 3H-1,25-(OH)2-vitamin D3 in healthy adults.

The synthesis of very high specific activity 25-OH-vitamin D3 (78 Ci/mmol) has made possible the study of the metabolism and plasma disappearance of 3H after a single dose of 3H-1,25-(OH)2-D3 in quantities that are only 10-20% of the endogenous plasma pool. We studied seven healthy adults who were given doses of 1,25-(OH)2-D3 ranging from 30-2300 pmol. Plasma disappearance was rapid with only 14 +/- 2% of administered 3H remaining in the plasma pool 4 h after labeling. Plasma metabolite profiles during the first 4 h showed only 1,25-(OH)2-D3. Thereafter, significant amounts of other metabolites were detected. The 6-day cumulative excretion of 3H in urine and feces (virtually all associated with metabolites of 1,25-(OH)2-D3) averaged 16 +/- 3% and 49 +/- 11% of the dose, respectively. Compartmental analysis of the isotope data for two subjects who received the smallest doses of 1,25-(OH)2-D3 indicated that endogenous renal 1,25-(OH)2-D3 synthesis rates approximate 0.8-2.4 nmol/day (0.3-1.0 microgram/day).

Adult

The importance of phosphate in regulating plasma 1,25-(OH)2-vitamin D levels in humans: studies in healthy subjects in calcium-stone formers and in patients with primary hyperparathyroidism.

We observed that plasma 1,25-(OH)2-D concentrations average 87 +/- 30 SD pmol/l in 48 healthy adults without a personal or family history of kidney stones. Plasma 1,25-(OH)2-D concentrations were significantly elevated among 26 patients with recurrent calcium-containing renal stones and hypophosphatemia: 150 +/- 74 pmol/l; P less than 0.001, and among 9 patients with proven parathyroid adenoma and hypophosphatemia: 200 +/- 54 pmol/l; P less than 0.001. Plasma 1,25-(OH)2-D levels in these 3 groups were inversely correlated with serum phosphate concentration: plasma 1,25-(OH)2-D, pmol/l = 282 - 141 X serum PO4, mmol/l; r = 0.51; P less than 0.001. During dietary PO4 deprivation lasting 11 to 16 days in 10 healthy women, serum PO4 fell and plasma 1,25-(OH)2-D concentrations rose whereas in 8 healthy men neither serum PO4 nor 1,25-(OH)2-D concentrations changed. The change from control in plasma 1,25-(OH)2-D levels were correlated with the change from control in serum PO4 concentrations: delta1,25-(OH)2-D, pmol/l = 1 - 82 X delta serum PO4 mmol/l; r = 0.59; P less than 0.01. We conclude that reductions in serum PO4 concentrations, either directly or indirectly, stimulate renal synthesis of 1,25-(OH)2-D in humans.

Adult

The lack of effect of chronic metabolic acidosis on 25-OH-vitamin D metabolism and serum parathyroid hormone in humans.

We evaluated the turnover of the plasma 25-OH-vitamin D pool, acid, and mineral balances in paired balance studies of 6 normal subjects during normal acid base conditions and during stable chronic metabolic acidosis induced by NH4Cl. Positive acid balances and negative Ca balances due to hypercalciuria were observed as previously reported. Plasma 25-OH-D pool turnover averaged 6.1+/-0.4 nmol/day during control and did not change during acidosis (6.5 +/- 0.5 nmol/day) nor were any significant increments in net intestinal absorption of Ca, PO4, or Mg, the physiological expression of vitamin D action, observed during acidosis. In 3 other subjects, repetitive measurements of serum iPTH during 7 control days and 24 days of stable NH4Cl acidosis showed no changes. We interpret the data to support the hypothesis that neither PTH nor vitamin D and its metabolites mediates the increase in net bone resorption that must accompany chronic metabolic acidosis.

Acidosis

Dietary phosphate deprivation in women and men: effects on mineral and acid balances, parathyroid hormone and the metabolism of 25-OH-vitamin D.

We evaluated the effects of dietary PO4 restriction on 25-OH-Vitamin D3 metabolism, serum iPTH levels, and mineral balances in healthy women and men. PO4 balances were progressively negative because of fecal losses without sex difference. Turnover of the plasma 25-OH-D pool was increased from 5.8 +/- 0.4 to 12 +/- 1.2 nmol/day; P less than 0.001, despite a fall in serum iPTH of -1.1 +/- 0.3 mulEq/ml; P less than 0.01. In both sexes, net intestinal calcium and magnesium absorption increased in proportion to a more rapid turnover of the plasma 25-OH-D pool, implying increased renal 1,25-(OH)2-D3 production. By contrast, there was a striking sex difference in the response of serum PO4 to dietary PO4 deprivation; the levels falling progressively in women, but remaining at control levels in men. Women demonstrated progressive hypercalciuria and negative Ca balances while in men the increments in intestinal Ca absorption were approximately matched by the increments in urinary Ca excretion so that Ca balances were not different from zero.

Adolescent