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Parathyroid Hormone Actions on Bone and Kidney

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Hypoparathyroidism

Abstract

Parathyroid hormone (PTH) acts on the kidney and bone through one common receptor in each organ. These actions, separately and together, serve to raise the blood calcium concentration. In the kidney, actions on the proximal tubule serve to decrease reabsorption of phosphorus and to activate the 1α-hydroxylase that leads to formation of active vitamin D. In the distal tubule, PTH serves to increase the reabsorption of calcium. In addition, actions of PTH on multiple cell types in bone also serve to regulate the proliferation and differentiation of these cell types. Here we consider the actions of PTH on its multiple target cells in the kidney and bone.

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References

  1. Rhee Y, Bivi N, Farrow E, Lezcano V, Plotkin LI, White KE et al (2011) Parathyroid hormone receptor signaling in osteocytes increases the expression of fibroblast growth factor-23 in vitro and in vivo. Bone 49(4):636–643. doi:10.1016/j.bone.2011.06.025. Epub 2011/07/06. doi: S8756-3282(11)01066-0 [pii] PubMed PMID: 21726676; PubMed Central PMCID: PMC3167030

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Juppner H, Abou-Samra AB, Freeman M, Kong XF, Schipani E, Richards J et al (1991) A G protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide. Science 254(5034):1024–1026

    Article  CAS  PubMed  Google Scholar 

  3. Fermor B, Skerry TM (1995) PTH/PTHrP receptor expression on osteoblasts and osteocytes but not resorbing bone surfaces in growing rats. J Bone Miner Res 10(12):1935–1943. PubMed PMID: 8619374

    Article  CAS  PubMed  Google Scholar 

  4. Karaplis AC, Luz A, Glowacki J, Bronson RT, Tybulewicz VL, Kronenberg HM et al (1994) Lethal skeletal dysplasia from targeted disruption of the parathyroid hormone-related peptide gene. Genes Dev 8(3):277–289. Epub 1994/02/01. PubMed PMID: 8314082

    Article  CAS  PubMed  Google Scholar 

  5. Miao D, He B, Lanske B, Bai XY, Tong XK, Hendy GN et al (2004) Skeletal abnormalities in Pth-null mice are influenced by dietary calcium. Endocrinology 145(4):2046–2053. doi:10.1210/en.2003-1097. Epub 2004/01/01. en.2003-1097 [pii]. PubMed PMID: 14701672

    Article  CAS  PubMed  Google Scholar 

  6. Lanske B, Karaplis AC, Lee K, Luz A, Vortkamp A, Pirro A et al (1996) PTH/PTHrP receptor in early development and Indian hedgehog-regulated bone growth [see comments]. Science 273(5275):663–666

    Article  CAS  PubMed  Google Scholar 

  7. Jobert AS, Zhang P, Couvineau A, Bonaventure J, Roume J, Le Merrer M et al (1998) Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia. J Clin Invest 102(1):34–40. doi:10.1172/JCI2918. Epub 1998/07/03. PubMed PMID: 9649554; PubMed Central PMCID: PMC509062

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Zhang P, Jobert AS, Couvineau A, Silve C (1998) A homozygous inactivating mutation in the parathyroid hormone/parathyroid hormone-related peptide receptor causing Blomstrand chondrodysplasia. J Clin Endocrinol Metab 83(9):3365–3368. doi:10.1210/jcem.83.9.5243. Epub 1998/09/24. PubMed PMID: 9745456

    Article  CAS  PubMed  Google Scholar 

  9. Bellows CG, Ishida H, Aubin JE, Heersche JN (1990) Parathyroid hormone reversibly suppresses the differentiation of osteoprogenitor cells into functional osteoblasts. Endocrinology 127(6):3111–3116. doi:10.1210/endo-127-6-3111. Epub 1990/12/01. PubMed PMID: 2174346

    Article  CAS  PubMed  Google Scholar 

  10. Huang JC, Sakata T, Pfleger LL, Bencsik M, Halloran BP, Bikle DD et al (2004) PTH differentially regulates expression of RANKL and OPG. J Bone Miner Res 19(2):235–244. doi:10.1359/JBMR.0301226. Epub 2004/02/19. PubMed PMID: 14969393

    Article  CAS  PubMed  Google Scholar 

  11. Isogai Y et al (1996) Parathyroid hormone regulates osteoblast differentiation positively or negatively depending on the differentiation stages. J Bone Miner Res 11:1384–1393. PMID: 888983

    Google Scholar 

  12. Ishizuya et al (1997) Parathyroid hormone exerts disparate effects on osteoblast differentiation depending on exposure time in rat osteoblastic cells. J Clin Invest 99:2961–2970. PMID: 9185520

    Google Scholar 

  13. Mendez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, Macarthur BD, Lira SA et al (2010) Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 466(7308):829–834. PubMed PMID: 20703299

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Schipani E, Kruse K, Juppner H (1995) A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia. Science 268(5207):98–100. PubMed PMID: 7701349

    Article  CAS  PubMed  Google Scholar 

  15. O’Brien CA, Plotkin LI, Galli C, Goellner JJ, Gortazar AR, Allen MR et al (2008) Control of bone mass and remodeling by PTH receptor signaling in osteocytes. PLoS One 3(8):e2942. doi:10.1371/journal.pone.0002942. Epub 2008/08/14. PubMed PMID: 18698360; PubMed Central PMCID: PMC2491588

    Article  PubMed Central  PubMed  Google Scholar 

  16. Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC et al (2003) Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425(6960):841–846. doi:10.1038/nature02040. Epub 2003/10/24. nature02040 [pii]. PubMed PMID: 14574413

    Article  CAS  PubMed  Google Scholar 

  17. Calvi LM, Bromberg O, Rhee Y, Weber JM, Smith JN, Basil MJ et al (2012) Osteoblastic expansion induced by parathyroid hormone receptor signaling in murine osteocytes is not sufficient to increase hematopoietic stem cells. Blood 119(11):2489–2499. doi:10.1182/blood-2011-06-360933. Epub 2012/01/21. doi: blood-2011-06-360933 [pii]. PubMed PMID: 22262765; PubMed Central PMCID: PMC3311272

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Saini V, Marengi DJ, Barry KJ, Fulzele KS, Heiden E, Liu X et al (2013) Parathyroid hormone (PTH)/PTH-related peptide type 1 receptor (PPR) signaling in osteocytes regulates anabolic and catabolic skeletal responses to PTH. J Biol Chem. doi:10.1074/jbc.M112.441360. Epub 2013/06/05. doi: M112.441360 [pii] PubMed PMID: 23729679

    Google Scholar 

  19. Kim SW, Pajevic PD, Selig M, Barry KJ, Yang JY, Shin CS et al (2012) Intermittent PTH administration converts quiescent lining cells to active osteoblasts. J Bone Miner Res. doi:10.1002/jbmr.1665. Epub 2012/05/25. PubMed PMID: 22623172

    Google Scholar 

  20. Dobnig H, Turner RT (1995) Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells. Endocrinology 136(8):3632–3638

    CAS  PubMed  Google Scholar 

  21. Leaffer D, Sweeney M, Kellerman LA, Avnur Z, Krstenansky JL, Vickery BH et al (1995) Modulation of osteogenic cell ultrastructure by RS-23581, an analog of human parathyroid hormone (PTH)-related peptide-(1–34), and bovine PTH-(1–34). Endocrinology 136(8):3624–3631

    CAS  PubMed  Google Scholar 

  22. Tam CS, Heersche JNM, Murray TM, Parsons JA (1982) Parathyroid hormone stimulates the bone apposition rate independently of its resorptive action: differential effects of intermittent and continuous administration. Endocrinology 110:506–512

    Article  CAS  PubMed  Google Scholar 

  23. Lotinun S, Sibonga JD, Turner RT (2005) Evidence that the cells responsible for marrow fibrosis in a rat model for hyperparathyroidism are preosteoblasts. Endocrinology 146(9):4074–4081. PubMed PMID: 15947001

    Article  CAS  PubMed  Google Scholar 

  24. Ishizuya T, Yokose S, Hori M, Noda T, Suda T, Yoshiki S et al (1997) Parathyroid hormone exerts disparate effects on osteoblast differentiation depending on exposure time in rat osteoblastic cells. J Clin Invest 99(12):2961–2970. doi:10.1172/JCI119491. Epub 1997/06/15. PubMed PMID: 9185520; PubMed Central PMCID: PMC508148

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Bellido T, Ali AA, Plotkin LI, Fu Q, Gubrij I, Roberson PK et al (2003) Proteasomal degradation of Runx2 shortens parathyroid hormone-induced anti-apoptotic signaling in osteoblasts. A putative explanation for why intermittent administration is needed for bone anabolism. J Biol Chem 278(50):50259–50272. PubMed PMID: 14523023

    Article  CAS  PubMed  Google Scholar 

  26. Jilka RL, Weinstein RS, Bellido T, Roberson P, Parfitt AM, Manolagas SC (1999) Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. [see comments.]. J Clin Invest 104(4):439–446

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Nishida S, Yamaguchi A, Tanizawa T, Endo N, Mashiba T, Uchiyama Y et al (1994) Increased bone formation by intermittent parathyroid hormone administration is due to the stimulation of proliferation and differentiation of osteoprogenitor cells in bone marrow. Bone 15:717–723

    Article  CAS  PubMed  Google Scholar 

  28. Robey PG, Kuznetsov SA, Riminucci M, Bianco P (2014) Bone marrow stromal cell assays: in vitro and in vivo. Methods Mol Biol 1130:279–293. doi:10.1007/978-1-62703-989-5_21. PubMed PMID: 24482181

    Article  PubMed Central  PubMed  Google Scholar 

  29. Murray TM, Rao LG, Divieti P, Bringhurst FR (2005) Parathyroid hormone secretion and action: evidence for discrete receptors for the carboxyl-terminal region and related biological actions of carboxyl- terminal ligands. Endocr Rev 26:78–113. PubMed PMID: 15546922

    Article  CAS  PubMed  Google Scholar 

  30. Potts JT, Gardella TJ (2007) Progress, paradox, and potential: parathyroid hormone research over five decades. Ann N Y Acad Sci 1117:196–208. doi:10.1196/annals.1402.088. PubMed PMID: 18056044

    Article  CAS  PubMed  Google Scholar 

  31. Vilardaga JP, Gardella TJ, Wehbi VL, Feinstein TN (2012) Non-canonical signaling of the PTH receptor. Trends Pharmacol Sci 33(8):423–431. doi:10.1016/j.tips.2012.05.004. PubMed PMID: 22709554; PubMed Central PMCID: PMC3428041

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Guo J, Liu M, Yang D, Bouxsein ML, Thomas CC, Schipani E et al (2010) Phospholipase C signaling via the parathyroid hormone (PTH)/PTH-related peptide receptor is essential for normal bone responses to PTH. Endocrinology 151(8):3502–3513. PubMed PMID: 20501677

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Qin L, Qiu P, Wang L, Li X, Swarthout JT, Soteropoulos P et al (2003) Gene expression profiles and transcription factors involved in parathyroid hormone signaling in osteoblasts revealed by microarray and bioinformatics. J Biol Chem 278(22):19723–19731. PubMed PMID: 12644456

    Article  CAS  PubMed  Google Scholar 

  34. Horwood NJ, Elliott J, Martin TJ, Gillespie MT (1998) Osteotropic agents regulate the expression of osteoclast differentiation factor and osteoprotegerin in osteoblastic stromal cells. Endocrinology 139(11):4743–4746

    Article  CAS  PubMed  Google Scholar 

  35. Jilka RL, O’Brien CA, Bartell SM, Weinstein RS, Manolagas SC (2010) Continuous elevation of PTH increases the number of osteoblasts via both osteoclast-dependent and -independent mechanisms. J Bone Miner Res 25(11):2427–2437. doi:10.1002/jbmr.145. PubMed PMID: 20533302; PubMed Central PMCID: PMC3179285

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Tang Y, Wu X, Lei W, Pang L, Wan C, Shi Z et al (2009) TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat Med 15(7):757–765. PubMed PMID: 19584867

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Takeshita S, Fumoto T, Matsuoka K, Park KA, Aburatani H, Kato S et al (2013) Osteoclast-secreted CTHRC1 in the coupling of bone resorption to formation. J Clin Invest 123(9):3914–3924. doi:10.1172/JCI69493. PubMed PMID: 23908115; PubMed Central PMCID: PMC3754269

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Guo J, Liu M, Yang D, Bouxsein ML, Saito H, Galvin RJ et al (2010) Suppression of Wnt signaling by Dkk1 attenuates PTH-mediated stromal cell response and new bone formation. Cell Metab 11(2):161–171. PubMed PMID: 20142103

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Bellido T, Ali AA, Gubrij I, Plotkin LI, Fu Q, O’Brien CA et al (2005) Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. Endocrinology 146(11):4577–4583. PubMed PMID: 16081646

    Article  CAS  PubMed  Google Scholar 

  40. Keller H, Kneissel M (2005) SOST is a target gene for PTH in bone. Bone 37(2):148–158. PubMed PMID: 15946907

    Article  CAS  PubMed  Google Scholar 

  41. Kramer I, Loots GG, Studer A, Keller H, Kneissel M (2010) Parathyroid hormone (PTH)-induced bone gain is blunted in SOST overexpressing and deficient mice. J Bone Miner Res 25(2):178–189. doi:10.1359/jbmr.090730. PubMed PMID: 19594304; PubMed Central PMCID: PMC3153379

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Wan M, Yang C, Li J, Wu X, Yuan H, Ma H et al (2008) Parathyroid hormone signaling through low-density lipoprotein-related protein 6. Genes Dev 22(21):2968–2979. PubMed PMID: 18981475

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Romero G, Sneddon WB, Yang Y, Wheeler D, Blair HC, Friedman PA (2010) Parathyroid hormone receptor directly interacts with dishevelled to regulate beta-Catenin signaling and osteoclastogenesis. J Biol Chem 285(19):14756–14763. doi:10.1074/jbc.M110.102970. PubMed PMID: 20212039; PubMed Central PMCID: PMC2863183

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Canalis E, Centrella M, Burch W, McCarthy TL (1989) Insulin-like growth factor I mediates selective anabolic effects of parathyroid hormone in bone cultures. J Clin Invest 83(1):60–65. PubMed PMID: 2910920

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Pfeilschifter J, Laukhuf F, Muller-Beckmann B, Blum W, Pfister T, Ziegler R (1995) Parathyroid hormone increases the concentration of insulin-like growth factor-I and transforming growth factor beta 1 in rat bone. J Clin Invest 96:767–774

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Wang Y, Nishida S, Boudignon BM, Burghardt A, Elalieh HZ, Hamilton MM et al (2007) IGF-I receptor is required for the anabolic actions of parathyroid hormone on bone. J Bone Miner Res 22(9):1329–1337. PubMed PMID: 17539737

    Article  CAS  PubMed  Google Scholar 

  47. Hurley MM, Okada Y, Xiao L, Tanaka Y, Ito M, Okimoto N et al (2006) Impaired bone anabolic response to parathyroid hormone in Fgf2−/− and Fgf2+/− mice. Biochem Biophys Res Commun 341(4):989–994. PubMed PMID: 16455048

    Article  CAS  PubMed  Google Scholar 

  48. Bergwitz C, Juppner H (2010) Regulation of phosphate homeostasis by PTH, vitamin D, and FGF23. Annu Rev Med 61:91–104

    Article  CAS  PubMed  Google Scholar 

  49. Esbrit P et al (2001) Parathyroid hormone-related protein as a renal regulating factor. From vessels to glomeruli and tubular epithelium. Am J Nephrol 21(3):179–184

    Article  CAS  PubMed  Google Scholar 

  50. Garabedian M et al (1972) Control of 25-hydroxycholecalciferol metabolism by parathyroid glands. Proc Natl Acad Sci U S A 69(7):1673–1676

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Korkor AB et al (1987) Evidence that stimulation of 1,25(OH)2D3 production in primary cultures of mouse kidney cells by cyclic AMP requires new protein synthesis. J Bone Miner Res 2(6):517–524

    Article  CAS  PubMed  Google Scholar 

  52. Gensure RC, Gardella TJ, Juppner H (2005) Parathyroid hormone and parathyroid hormone-related peptide, and their receptors. Biochem Biophys Res Commun 328(3):666–678

    Article  CAS  PubMed  Google Scholar 

  53. Bringhurst FR et al (1993) Cloned, stably expressed parathyroid hormone (PTH)/PTH-related peptide receptors activate multiple messenger signals and biological responses in LLC-PK1 kidney cells. Endocrinology 132(5):2090–2098

    CAS  PubMed  Google Scholar 

  54. Janulis M, Tembe V, Favus MJ (1992) Role of protein kinase C in parathyroid hormone stimulation of renal 1,25-dihydroxyvitamin D3 secretion. J Clin Invest 90(6):2278–2283

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Henry HL (1985) Parathyroid hormone modulation of 25-hydroxyvitamin D3 metabolism by cultured chick kidney cells is mimicked and enhanced by forskolin. Endocrinology 116(2):503–510

    Article  CAS  PubMed  Google Scholar 

  56. Guo J et al (2002) The PTH/PTHrP receptor can delay chondrocyte hypertrophy in vivo without activating phospholipase C. Dev Cell 3(2):183–194

    Article  CAS  PubMed  Google Scholar 

  57. Guo J et al (2013) Activation of a non-cAMP/PKA signaling pathway downstream of the PTH/PTHrP receptor is essential for a sustained hypophosphatemic response to PTH infusion in male mice. Endocrinology 154(5):1680–1689

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Shinki T et al (1997) Cloning and expression of rat 25-hydroxyvitamin D3-1alpha-hydroxylase cDNA. Proc Natl Acad Sci U S A 94(24):12920–12925

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Takeyama K et al (1997) 25-Hydroxyvitamin D3 1alpha-hydroxylase and vitamin D synthesis. Science 277(5333):1827–1830

    Article  CAS  PubMed  Google Scholar 

  60. St-Arnaud R et al (1997) The 25-hydroxyvitamin D 1-alpha-hydroxylase gene maps to the pseudovitamin D-deficiency rickets (PDDR) disease locus. J Bone Miner Res 12(10):1552–1559

    Article  CAS  PubMed  Google Scholar 

  61. Brenza HL et al (1998) Parathyroid hormone activation of the 25-hydroxyvitamin D3-1alpha-hydroxylase gene promoter. Proc Natl Acad Sci U S A 95(4):1387–1391

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Murayama A et al (1998) The promoter of the human 25-hydroxyvitamin D3 1 alpha-hydroxylase gene confers positive and negative responsiveness to PTH, calcitonin, and 1 alpha,25(OH)2D3. Biochem Biophys Res Commun 249(1):11–16

    Article  CAS  PubMed  Google Scholar 

  63. Hendrix I et al (2005) Response of the 5′-flanking region of the human 25-hydroxyvitamin D 1alpha-hydroxylase gene to physiological stimuli using a transgenic mouse model. J Mol Endocrinol 34(1):237–245

    Article  CAS  PubMed  Google Scholar 

  64. Zierold C, Nehring JA, DeLuca HF (2007) Nuclear receptor 4A2 and C/EBPbeta regulate the parathyroid hormone-mediated transcriptional regulation of the 25-hydroxyvitamin D3-1alpha-hydroxylase. Arch Biochem Biophys 460(2):233–239

    Article  CAS  PubMed  Google Scholar 

  65. Gao XH et al (2002) Basal and parathyroid hormone induced expression of the human 25-hydroxyvitamin D 1alpha-hydroxylase gene promoter in kidney AOK-B50 cells: role of Sp1, Ets and CCAAT box protein binding sites. Int J Biochem Cell Biol 34(8):921–930

    Article  CAS  PubMed  Google Scholar 

  66. Murayama A et al (1999) Positive and negative regulations of the renal 25-hydroxyvitamin D3 1alpha-hydroxylase gene by parathyroid hormone, calcitonin, and 1alpha,25(OH)2D3 in intact animals. Endocrinology 140(5):2224–2231

    CAS  PubMed  Google Scholar 

  67. Murayama A et al (2004) Transrepression by a liganded nuclear receptor via a bHLH activator through co-regulator switching. EMBO J 23(7):1598–1608

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Anderson PH et al (2008) Co-expression of CYP27B1 enzyme with the 1.5 kb CYP27B1 promoter-luciferase transgene in the mouse. Mol Cell Endocrinol 285(1–2):1–9

    Article  CAS  PubMed  Google Scholar 

  69. Young MV et al (2004) The prostate 25-hydroxyvitamin D-1 alpha-hydroxylase is not influenced by parathyroid hormone and calcium: implications for prostate cancer chemoprevention by vitamin D. Carcinogenesis 25(6):967–971

    Article  CAS  PubMed  Google Scholar 

  70. Biber J et al (1996) Renal Na/Pi-cotransporters. Kidney Int 49(4):981–985

    Article  CAS  PubMed  Google Scholar 

  71. Pfister MF et al (1998) Parathyroid hormone leads to the lysosomal degradation of the renal type II Na/Pi cotransporter. Proc Natl Acad Sci U S A 95(4):1909–1914

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  72. Weinman EJ, Lederer ED (2012) PTH-mediated inhibition of the renal transport of phosphate. Exp Cell Res 318(9):1027–1032

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  73. Shenolikar S et al (2002) Targeted disruption of the mouse NHERF-1 gene promotes internalization of proximal tubule sodium-phosphate cotransporter type IIa and renal phosphate wasting. Proc Natl Acad Sci U S A 99(17):11470–11475

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  74. Hernando N et al (2002) PDZ-domain interactions and apical expression of type IIa Na/P(i) cotransporters. Proc Natl Acad Sci U S A 99(18):11957–11962

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  75. Karim Z et al (2008) NHERF1 mutations and responsiveness of renal parathyroid hormone. N Engl J Med 359(11):1128–1135

    Article  CAS  PubMed  Google Scholar 

  76. Cunningham R et al (2006) Adenoviral expression of NHERF-1 in NHERF-1 null mouse renal proximal tubule cells restores Npt2a regulation by low phosphate media and parathyroid hormone. Am J Physiol Renal Physiol 291(4):F896–F901

    Article  CAS  PubMed  Google Scholar 

  77. Weinman EJ et al (2007) Parathyroid hormone inhibits renal phosphate transport by phosphorylation of serine 77 of sodium-hydrogen exchanger regulatory factor-1. J Clin Invest 117(11):3412–3420

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  78. Mahon MJ et al (2002) Na(+)/H(+) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling. Nature 417(6891):858–861

    Article  CAS  PubMed  Google Scholar 

  79. Wang B et al (2012) Ezrin-anchored protein kinase A coordinates phosphorylation-dependent disassembly of a NHERF1 ternary complex to regulate hormone-sensitive phosphate transport. J Biol Chem 287(29):24148–24163

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  80. Guo J et al (2012) Fluorescent ligand-directed co-localization of the parathyroid hormone 1 receptor with the brush-border scaffold complex of the proximal tubule reveals hormone-dependent changes in ezrin immunoreactivity consistent with inactivation. Biochim Biophys Acta 1823(12):2243–2253

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  81. Nagai S et al (2011) Acute down-regulation of sodium-dependent phosphate transporter NPT2a involves predominantly the cAMP/PKA pathway as revealed by signaling-selective parathyroid hormone analogs. J Biol Chem 286(2):1618–1626

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  82. Lau K, Bourdeau JE (1995) Parathyroid hormone action in calcium transport in the distal nephron. Curr Opin Nephrol Hypertens 4(1):55–63

    Article  CAS  PubMed  Google Scholar 

  83. Bourdeau JE, Lau K (1989) Effects of parathyroid hormone on cytosolic free calcium concentration in individual rabbit connecting tubules. J Clin Invest 83(2):373–379

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  84. Lau K, Bourdeau JE (1989) Evidence for cAMP-dependent protein kinase in mediating the parathyroid hormone-stimulated rise in cytosolic free calcium in rabbit connecting tubules. J Biol Chem 264(7):4028–4032

    CAS  PubMed  Google Scholar 

  85. Hoenderop JG et al (2003) Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5. J Clin Invest 112(12):1906–1914

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  86. Hoenderop JG, Nilius B, Bindels RJ (2002) Molecular mechanism of active Ca2+ reabsorption in the distal nephron. Annu Rev Physiol 64:529–549

    Article  CAS  PubMed  Google Scholar 

  87. van Abel M et al (2005) Coordinated control of renal Ca(2+) transport proteins by parathyroid hormone. Kidney Int 68(4):1708–1721

    Article  PubMed  Google Scholar 

  88. Cha SK, Wu T, Huang CL (2008) Protein kinase C inhibits caveolae-mediated endocytosis of TRPV5. Am J Physiol Renal Physiol 294(5):F1212–F1221

    Article  CAS  PubMed  Google Scholar 

  89. de Groot T et al (2009) Parathyroid hormone activates TRPV5 via PKA-dependent phosphorylation. J Am Soc Nephrol 20(8):1693–1704

    Article  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, 50 Blossom St., Thier 1101, Boston, MA, 02114, USA

    Paola Divieti Pajevic, Marc N. Wein & Henry M. Kronenberg

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  1. Paola Divieti Pajevic
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  2. Marc N. Wein
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  3. Henry M. Kronenberg
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Correspondence to Henry M. Kronenberg .

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Editors and Affiliations

  1. Unit of Metabolic and Bone Diseases, University of Florence, Florence, Italy

    Maria Luisa Brandi

  2. Division of Endocrinology, Diabetes and Hypertension, Harvard Medical School and Brigham & Women's Hospital, Boston, Massachusetts, USA

    Edward Meigs Brown

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Pajevic, P.D., Wein, M.N., Kronenberg, H.M. (2015). Parathyroid Hormone Actions on Bone and Kidney. In: Brandi, M., Brown, E. (eds) Hypoparathyroidism. Springer, Milano. https://doi.org/10.1007/978-88-470-5376-2_11

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