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Long-term administration of vitamin D3 metabolites alters PTH-responsive osteoblastic adenylate cyclase in rats

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Summary

We have examined the effect of induced hyper D3 vitaminosis on bone-related variables in the rat with special reference to the parathyroid (PTH)-sensitive adenylate cyclase (AC) in rat calvariae. Subcutaneous injections three times a week of doses theoretically corresponding to about 10 times the average physiological serum levels of either 25 hydroxyvitamin D3 (25OHD3), 1,25 dihydroxyvitamin D3 (1,25(OH)2D3), or 24,25 dihydroxyvitamin D3 (24,25(OH)2D3) for 12 weeks gave the following results: At 12 weeks of treatment, 24,25(OH)2D3 levels in the groups receiving 25OHD3 or 24,25(OH)2D3 increased significantly, whereas 1,25(OH)2D3 levels remained unaffected. Correspondingly, PTH-sensitive AC activities in crude calvarial membrane fractions from 25OHD3-and 24,25(OH)2D3-treated animals were obliterated. This effect was apparent after 4 weeks of treatment. In the group receiving 25OHD3, both basal, plus Gpp(NH)p-, and forskolin-sensitive AC activities were significantly reduced after 4 weeks of treatment. Similar effects in crude kidney membrane fractions were, however, not observed. Liver membranes from 25OHD3- or 24,25(OH)2D3-treated animals showed insignificant changes in the isoprenalin-, PGE1-, Gpp(NH)p-, or forskolin-sensitive AC activities. Finally, the significance of reduced PTH-sensitive bone AC activity has been assessed. 25OHD3 treatment yielded normocalcemic and hypercalciuric rats, whereas 1,25(OH)2D3 enhanced both serum and urine Ca2+ levels. 24,25(OH)2D3-treated and control animals were undiscernible in this respect. However, the 24,25-(OH)2D3 treatment caused reductions in both serum alkaline phosphatase levels and urinary hydroxyproline/creatinine ratio. These results indicate that administration of vitamin D3 metabolites which increase serum 24,25(OH)2D3 levels without affecting renal handling of Ca2+, obliterates the PTH-sensitive AC in bone, thereby altering bone turnover.

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References

  1. Endo H, Kiyoki M, Kawashima K, Naruchi T, Hashimoto Y (1980) Vitamin D3 metabolites and PTH synergistically stimulate bone formation of chick embryonic femur in vitro. Nature 286:262–264

    Article  PubMed  CAS  Google Scholar 

  2. Van Diemen-Steenvoorde R, Donckerwolcke RA, Bosch R, Visser WJ, Raymakers JA, Duursma SA (1985) Treatment of renal osteodystrophy in children with dihydrotachysterol and 24,25-dihydroxyvitamin D3. Clin Nephrology 24(6):292–299

    Google Scholar 

  3. Dickson I (1987) New approaches to vitamin D. Nature 325:18

    Article  PubMed  CAS  Google Scholar 

  4. Martin CR (1985) Functions of calcium, phosphorus, and calciferols. Endocrine physiology. Oxford University Press, New York, pp 409–462

    Google Scholar 

  5. Manolagas SC, Deftos LJ (1981) Comparison of 1,25-, 25-, and 24,25-hydroxylated vitamin D3 binding in fetal rat calvariae and osteogenic sarcoma cells. Calcif Tissue Int 33:655–661

    Article  PubMed  CAS  Google Scholar 

  6. Lidor C, Atkin I, Ornoy A, Dekel S, Edelstein S (1987) Healing of rachitic lesions in chicks by 24R,25-dihydroxycholecalciferol administered locally into bone. J Bone Min Res 2:91–98

    CAS  Google Scholar 

  7. Gordeladze JO, Gautvik KM (1986) Hydroxycholecalciferols modulate parathyroid hormone and calcitonin sensitive adenylyl cyclase in bone and kidney of rats. Biochem Pharm 35(6):899–902

    Article  PubMed  CAS  Google Scholar 

  8. Klem KH, Jablonski G, Sæther O, Jarosz G, Gautvik KM, Gordeladze JO (1990) Immediate and long term effects of vitamin-D3 metabolites on parathormone (PTH) sensitive adenylate cyclase activity and alkaline phosphatase secretion of osteoblastic cells. Biochim Biophys Acta (in press)

  9. Jablonski G, Klem KH, Nordal K, Halse J, Dahl E, Aksnes L, Gautvik KM, Gordeladze JO (1990) PTH-stimulated adenylate cyclase activity in iliac crest biopsies, bone histomorphometry and clinical chemistry determine the evaluation of uremic patients: a pilot study with the use of artifical intelligence. Scand J Clin Lab Invest (in press)

  10. Chan Y-L, Mason RS, Parmentier M, Savdie E, Lissner D, Posen S (1983) Vitamin D metabolism in nephrotic rats. Kidney Int 24:336–341

    PubMed  CAS  Google Scholar 

  11. Aksnes L (1980) Quantitation of the main metabolites of vitamin D in a single serum sample. I. Extraction, separation and purification of metabolites. Clin Chim Acta 104:133–146

    Article  PubMed  CAS  Google Scholar 

  12. Aksnes L (1980) Quantitation of the main metabolites of vitamin D in a single serum sample. II. Determination by UV-absorption and competitive protein binding assays. Clin Chim Acta 104:147–159

    Article  PubMed  CAS  Google Scholar 

  13. Kastrup EK, Boyd JR, Olin BR, Hunsaker LM (1985) Drug facts and comparisons. Lippincott Company, Philadelphia, pp 9–13

    Google Scholar 

  14. Catherwood BD (1985) 1,25-dihydroxycholecalciferol and glucocorticosteroid regulation of adenylate cyclase in an osteoblast-like cell line. J Biol Chem 260:736–743

    PubMed  CAS  Google Scholar 

  15. Gautvik KM, Gordeladze JO, Jahnsen T, Haug E, Hansson V, Lystad E (1983) Thyroliberin receptor binding and adenylyl cyclase activation in cultured prolactin-producing rat pituitary tumor cells (GH cells). J Biol Chem 258:10304–10311

    PubMed  CAS  Google Scholar 

  16. Gautvik KM, Gordeladze JO, Moxheim E, Gautvik VT (1984) Peripheral metabolism of parathyroid hormone in patients with primary hyperparathyroidism as judged by immunological and biological studies. Eur Surg Res 16:41–54

    PubMed  CAS  Google Scholar 

  17. Birnbaumer L, Yang P-C, Hunzicker-Dunn M, Bockaert J, Duran JM (1976) Adenylyl cyclase activities in ovarian tissues. I. Homogenization and conditions of assay in Graafian follicles and corpora lutea of rabbits, rats and pigs: regulation by ATP, and some comparative properties. Endocrinology 99:163–184

    PubMed  CAS  Google Scholar 

  18. Gautvik KM, Teig V, Halvorsen JF, Arnesen E, Myhre L, Heimann P, Tollmann R (1979) Development of sequence-specific radioimmunoassay of human parathyroid hormone and its use in the diagnosis of hyperparathyroidism. Scand J Clin Lab Invest 39:469–478

    PubMed  CAS  Google Scholar 

  19. Gordeladze JO, Halse J, Djøseland O, Haugen HN (1978) A simple procedure for the determination of hydroxyproline in urine and bone. Biochem Med 20:23–30

    Article  PubMed  CAS  Google Scholar 

  20. Chen TL, Feldman D (1984) Modulation of PTH-stimulated cyclic AMP in cultured rodent bone cells: the effects of 1,25(OH)2 vitamin D3 and its interaction with glucocorticoids. Calcif Tissue Int 36:580–585

    Article  PubMed  CAS  Google Scholar 

  21. Wong GL, Luben RA, Cohn DV (1977) 1,25-dihydroxycholecalciferol and parathormone: effects on isolated osteoclast-like and osteoblast-like cells. Science 197:663–665.

    Article  PubMed  CAS  Google Scholar 

  22. Kent GN, Jilka RL, Cohn DV (1980) Homologous and heterologous control of bone cell adenosine 3′5′-monophosphate response to hormones by parathormone, prostaglandin E2, calcitonin, and 1,25-dihydroxycholecalciferol. Endocrinology 107:1474–1481

    PubMed  CAS  Google Scholar 

  23. Marcus R, Orner FB, Brickmann AS (1980) Effects of vivo of vitamin D metabolites and 17-beta-estradiol on parathyroid hormone-dependent formation of adenosine 3′,5′-monophosphate in rat bone. Endocrinology 107:1593–1599

    PubMed  CAS  Google Scholar 

  24. Majeska RJ, Rodan GA (1982) The effect of 1,25(OH)2D3 on alkaline phosphatase in osteoblastic osteosarcoma cells. J Biol Chem 257:3362–3365

    PubMed  CAS  Google Scholar 

  25. Bradbeer JN, Mehdizadeh S, Fraher LJ, Loveridge N (1988) Certain vitamin D metabolites potentiate the expression of parathyroid hormone bioactivity. J Bone Min Res 3(1):47–52

    Article  CAS  Google Scholar 

  26. Maghoub A, Sheppard H (1975) Early effect of 25-hydroxycholecalciferols (25-OH-D3) and 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) on the ability of parathyroid hormone (PTH) to elevate cyclic AMP of intact bone cells. Biochem Biophys Res Commun 62:901–907

    Article  Google Scholar 

  27. Gordeladze JO, Mortensen B, Nordal K, Halse J, Dahl E, Aksnes L, Gautvik KM (1987) The effect of parathyroid hormone (PTH) and 24,25-dihydroxy-vitamin D3 on adenylyl cyclase of iliac crest biopsies: diagnostic and prognostic tool for evaluation and treatment of uremic patients. Scand J Clin Lab Invest 47 (suppl 186):13–20

    Article  Google Scholar 

  28. Halloran BP, Bikle DB, Castro ME (1987) 1,25 dihydroxy-vitamin D administration increases the metabolic clearance rates of 1,25(OH)2D and 24,25(OH)2D. J Bone Min Res 2 (suppl 1) [abstract 442]

    Google Scholar 

  29. Matsumoto T, Yamamoto H, Fukumoto S, Morita K, Ogata E (1987) Effect of 24,25-dihydroxyvitamin D3 on metabolic clearance of 1,25-dihydroxyvitamin D3 in rats. J Bone Min Res 2 (suppl 1) [abstract 437]

    Google Scholar 

  30. Fritsch J, Grosse B, Lieberherr M, Balsan S (1985) 1,25-dihydroxyvitamin D3 is required for growth-independent expression of alkaline phosphatase in cultured rat osteoblasts. Calcif Tissue Int 37:639–645

    Article  PubMed  CAS  Google Scholar 

  31. Halse J, Gordeladze JO (1978) Urinary hydroxyproline excretion in acromegaly. Acta Endocrinol (Copenh) 89:483–491

    CAS  Google Scholar 

  32. Halse J, Gordeladze JO (1981) Total and non-dialyzable urinary hydroxyproline in acromegalics and control subjects. Acta Endocrinol (Copenh) 96:451–457

    CAS  Google Scholar 

  33. Schwartz Z, Schlader DL, Swain LD, Boyan BD (1988) Direct effects of 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 on growth zone and resting zone chondrocyte membrane alkaline phosphatase and phospholipase-A2 specific activities. Endocrinology 123(6):2878–2884

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Medical Biochemistry, University of Oslo, Oslo, Norway

    Berit Mortensen, Jan O. Gordeladze & Kaare M. Gautvik

  2. Department of Pediatrics, University of Bergen, Haukeland Hospital, Bergen, Norway

    Lage Aksnes

  3. Institute for Surgical Research, The National Hospital, 0027, Oslo 1, Norway

    Berit Mortensen, Jan O. Gordeladze & Kaare M. Gautvik

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  1. Berit Mortensen
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  4. Kaare M. Gautvik
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Mortensen, B., Gordeladze, J.O., Aksnes, L. et al. Long-term administration of vitamin D3 metabolites alters PTH-responsive osteoblastic adenylate cyclase in rats. Calcif Tissue Int 46, 339–345 (1990). https://doi.org/10.1007/BF02563826

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  • DOI: https://doi.org/10.1007/BF02563826

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