Blood levels of ionized calcium, inorganic phosphorus, 1,25-dihydroxycholecalciferol and gonadal hormones in hens laying hard-shelled or shell-less eggs.

The production of shell-less eggs was induced in hens to measure the effects of the high demands made by shell formation on the blood minerals and hormones whose concentrations change during egg formation. In control hens laying hard-shelled eggs, the concentration of ionized calcium in plasma decreased at the onset of shell formation, but no change was found in hens laying shell-less eggs. Total calcium concentrations in plasma decreased slightly throughout the ovulation cycle in both groups. Concentrations of inorganic phosphorus in the plasma were increased in the control group during the period of shell formation and decreased when calcification was suppressed. Finally, the concentrations of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) in plasma were significantly increased 16 and 20 h following an ovulation compared with 4 h after ovulation, or compared with the concentrations observed in hens laying shell-less eggs. The variations in the plasma concentrations of ionized calcium, inorganic phosphorus and 1,25-(OH)2D3 associated with egg formation were therefore absent in hens laying shell-less eggs demonstrating their direct link with shell calcification. On the other hand, suppression of shell production had no influence on the changes in the plasma concentrations of progesterone, oestradiol and testosterone which are associated with the normal ovulatory cycle. It is concluded that the increases in intestinal and uterine calcium transport and in 1,25-(OH)2D3 production which occur at the onset of egg production in hens are mainly controlled by factors involved in maintaining calcium homeostasis rather than by gonadal hormones.

Involvement of 1,25-dihydroxycholecalciferol in the short- and long-term increase of intestinal calcium absorption in laying hens: stimulation by gonadal hormones is partly independent of 1,25-dihydroxycholecalciferol.

The short- and long-term effects of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and its interactions with sexual steroids on Ca absorption were studied in hens. A single injection of 375 ng 1,25(OH)2D3 did not increase intestinal calcium transport in D-repleted hens within 24 hr of administration. However, five daily injections of 1 alpha-(OH)D3(0.5 micrograms/kg), a low Ca intake, or oestrogen-testosterone (O.T) did increase calcium absorption in D-repleted immature pullets (measured by in vivo perfusion), mainly by increasing the diffusional component of Ca transport. O.T. further increased the stimulation by 1 alpha-(OH)D3 of calcium absorption and of duodenal CaBP concentration. At higher doses the stimulation by 1 alpha-(OH)D3 of calcium transport estimated by in situ ligated loop procedure was dose dependent and was not saturable at daily doses of less than 3 micrograms/kg. When Ca transport was stimulated by 2 micrograms/kg of 1 alpha-(OH)D3, an additional effect of O.T. was observed again without any increase in plasma levels of 1,25(OH)2D3. Both oestrogen and testosterone were necessary for this effect on Ca transport. This is evidence for an indirect effect on Ca transport, as both steroids are also necessary to induce medullary bone. It is concluded that O.T. increased intestinal absorption of calcium, first by stimulating 25(OH)D3 1 alpha-hydroxylase activity but also by another mechanism which is independent of 1,25(OH)2D3 metabolism.

Possible link between changes in plasma 24,25-dihydroxyvitamin D and healing of bone resorption in dialysis osteodystrophy.

Histomorphometric studies of bone biopsies were performed on 12 hemodialyzed patients before and after six months of treatment with 25-(OH) and 1 alpha-(OH) vitamin D3. Patients could be classified into three groups according to bone resorption: Group I with normal bone resorption; Group II with elevated initial bone resorption unresponsive to vitamin D treatment; group III with elevated initial bone resorption sensitive to vitamin D treatment. None of the patients had histological signs of osteomalacia. In Group I, plasma concentrations of 24,25-(OH)2D and the ratio of 24,25-(OH)2D to 25-(OH) D remained in the normal range throughout the study; in Group II these parameters were subnormal initially and did not increase above normal except in one case; in Group III, plasma concentrations of 24,25-(OH)2D were high before or at the beginning of vitamin D administration and normal at the time of the second biopsy and wide variations were observed in the ratio of 24,25-(OH)2D to 25-(OH)D. No difference was found between these last two groups with regard to the cumulative dose of vitamin D derivatives administered or the changes in plasma PTH, CT, calcium and phosphate. These observations suggest a specific regulation of plasma 24,25-(OH)2D concentrations in hemodialyzed patients and a possible link (independent of circulating PTH, CT, or phosphate) between this regulation and healing of bone resorption. However, no correlation was found between plasma 24,25-(OH)2D and either one of the simultaneously measured biochemical or histological parameters.

[Measurements of plasma concentrations of active vitamin D metabolites in children: interest and limit (author's transl)]. / Mesure des taux circulants des métabolites actifs de la vitamine D chez l'enfant. Intérêt et limites.

This study of the three main vitamin D metabolites namely 25-(OH) D, 24, 25-(OH) 2D and 1, 25-(OH) 2D includes (1) a summary of the usual assay techniques, (2) a discussion about the concentrations and the role of these metabolites during the neonatal and childhood periods, (3) a report of the results obtained during the past seven years in our laboratory with comments on the interest and limits of these assays for the diagnosis of different types of rickets.

The in vitro production and activity of 24, 25-dihydroxycholecalciferol in cartilage and calvarium.

Previously reported results from our laboratory have indicated that 24, 25-dihydroxycholecalciferol can be formed in vitro during incubations of cartilage tissue or cartilage cells with 25-hydroxycholecalcified. They have also demonstrated the high potency of this dihydroxymetabolite of vitamin D3 in stimulating in vitro the sulfate incorporation into proteoglycans of cartilage cells in culture and in decreasing in vitro the parathyroid hormone action on rat calvarium phosphatases activities. The present report shows that 24, 25-)OH)2 D3 can also be produced during rat calvarium incubations with 25-hydroxycholecalciferol and that therefore calvarium as well as cartilage might be both a site of formation and a site of action for 24, 25-(OH)2 D3. The review of recent experimental and clinical investigations strongly suggests that this metabolite has a physiological significance and may be specifically active on some parameters of bone mineralization. Further studies on the cartilage and calvarium abilities to convert 25-hydroxycholecalciferol into 24, 25-(OH)2 D3 shows that this transformation occurs in the mitochondrial fraction but that it does not seem modified by factors known to control the 25-hydroxycholecalciferol metabolism in the kidney. Finally the analysis of experimental and clinical results published so far does not yet bring enough information to understand the significance of this extrarenal metabolism of 25-hydroxycholecalciferol.