Enterohepatic physiology of 1,25-dihydroxyvitamin D3.

Kumar, Rajiv; Nagubandi, Sreeramulu; Mattox, Vernon R.; Londowski, James M.

doi:10.1172/jci109669

Cited by 90 publications

(25 citation statements)

References 12 publications

(9 reference statements)

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“…Five-milliliter fractions of the eluate were collected, an aliquot of each fraction was transferred to a 5-ml scintillation vial and dried, and radioactivity was determined (20). After chromatography, the Sephadex LH-20 in the column was washed with methanol.…”

Section: Gray Et Al (5) Administeredmentioning

confidence: 99%

Do tissues other than the kidney produce 1,25-dihydroxyvitamin D3 in vivo? A reexamination.

Shultz¹,

Fox²,

Heath³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

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Recent experiments have shown that 1,25-dihydroxyvitamin D3-like material is produced in cultured nonrenal cells and may be present in the sera of anephric patients. We reexamined the question of whether 1,25-dihydroxyvitamin D3 can be synthesized extrarenally in the rat in vivo. To intact, sham-operated, ureter-ligated, or acutely nephrectomized vitamin D-deficient rats raised on a diet normal in calcium and phosphorus, we gave a physiologic dose of high-specific-activity 25-hydroxy-[3H]vitaminD3(3.6-3.81uCi; -25pmolper rat). Twenty-fourhours later we examined their tissues and plasma for the presence of radiolabeled 1,25-dihydroxyvitamin D3. Large amounts of radioactivity that behaved chromatographically as identical with authentic 1,25-dihydroxyvitamin D3 were present in the plasma, bone, and intestine of the intact, sham-operated, or ureter-ligated rats. However, no radioactivity eluting in a manner similar to 1,25-dihydroxyvitamin D3 was found in plasma, bone, or intestine of acutely nephrectomized rats. We conclude that, in the acutely nephrectomized living rat, 1,25-dihydroxyvitamin D3 is not present in plasma, bone, or intestine in quantities detectable by the sensitive techniques we have used. No conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 was observed during a 24-hr period after nephrectomy of vitamin D-deprived rats. This fact casts doubt upon the significance of the in vitro production of 1,25-dihydroxyvitamin D3 by nonrenal cells as an in vivo phenomenon. Gray et al. (3), found that radiolabeled 1,25(OH)2D3 was absent from the tissues and plasma of acutely nephrectomized rats that had received low-specific-activity radiolabeled vitamin D3 or 25(OH)D3 immediately after nephrectomy. In human anephric subjects given radiolabeled vitamin D3, Mawer et aL (4) failed to detect radioactive 1,25(OH)2D3. Gray et al. (5) administered 25(OH)[3H]D3to 10 anephric subjects; in none of the patients studied was radiolabeled 1,25(OH)2D3 detected. In these human studies, radiolabeled 1,25(OH)2D3 was clearly detectable in normal subjects (4, 5). Lambert et al. (6) found recently that a substance was present in the plasma ofanephric subjects that displaced 1,25(OH)2[3H]D3 from its receptor; additionally, samples processed in a similar manner displaced 45Ca from labeled fetal bone in a bioassay system for 1,25(OH)2D3. The authors concluded that 1,25(OH)2D3 was present in the plasma of anephric subjects. However, other investigators, using radioreceptor, radioimmune, and biological assays for 1,25(OH)2D3, have been unable to detect 1,25(OH)2D3 in anephric persons (7-12).In certain situations, however, 1,25(OH)2D3 may be synthesized extrarenally. For example, a report by Barbour et al. (13) showed that an anephric subject with sarcoidosis had detectable plasma 1,25(OH)2D3-like material at a time when he was hypercalcemic (13)

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Section: Gray Et Al (5) Administeredmentioning

confidence: 99%

Do tissues other than the kidney produce 1,25-dihydroxyvitamin D3 in vivo? A reexamination.

Shultz¹,

Fox²,

Heath³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

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“…The PTH antiserum employed, GP1I, reacts primarily with determinants in the 44-68 region of the PTH molecule (26) and is par-ticularly sensitive for detection of increased parathyroid gland fuinetion (27 (29). Radioactivity in 2-ml plasma samllples was determliineI by direct scintillation counting.…”

Section: Introductionmentioning

confidence: 99%

Production, degradation, and circulating levels of 1,25-dihydroxyvitamin D in health and in chronic glucocorticoid excess.

Kumar²,

et al. 1980

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A B S T R A C T The decreasedl intestinal absorption of calcium and accelerated l)one loss associate(l with chronic glucocorticoid excess may be mediated by changes in vitamin D metabolism, leading to dlecreased availability of circulating 1,25-dihydroxyvitamin D. This hypothesis was examined in 14 patients with either endogenous or exogenous glucocorticoid excess. Analysis of paired serum samples (mean ±SE) in 13 patients duiring euglucocorticoidlisml-and dutring hyperglucocorticoidism showed that glucocorticoid excess resulted in small decreases of plasma 25-hydroxyvitamin D concentrations (22+2-18±2 ng/ml; P < 0.05) lbut no significant chaniges in plasmiia 1,25-dihydroxyvitamini D (32 ± 8-23±+46 pg/ml) or serum immunoreactive parathyroi(l hormone (21±2-18±2 ,uleq/ml). Additionally, we studied plasmna kinetics of[3H] 1 ,25-dihydroxyvitamin D3 after intravenotus bolus administration in 10 hyperglucocorticoid patients and in 14 normal controls. Assessmiient with a threecompartment model showe(d no significant abnormalities in production rates (hyperglucocorticoid patients 1.2±0.3 ,g/d, controls 1.5±0.2 ,ugld) or metabolic clearance rates (hyperglucocorticoid patients, 32 ± 3 ml/ min; controls 31+3 ml/min). Moreover, there were no significant differences in ciumulative excretion of radioactivity in urine (hyperglutcocorticoid patieints 18±2%; controls, 14±2%) or f'eces (hyperglucocorticoid patients, 60±9%, controls, 54+6%). We conclude that glucocorticoid excess does not effect plasma levels, production, or degradation of 1,25(OH)2D in hunIans. Thus, other mechanisms mutst be postulated to explain satisfactorily the abnormialities of bone structure and intestinal calciumn absorption that maiy occur after chronic glucocoi-ticoidl therapy.

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“…Production of calcitroic acid in target tissues may be an important mechanism for inactivation of the biologically potent 1,25(OH)2D. In addition, 1,25(OH)2D undergoes an enterohepatic circulation, as shown in rat (9) and humans (10).…”

Section: Metabolism Of Vitamin Dmentioning

confidence: 99%