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Nitric oxide synthase in human parathyroid glands and parathyroid adenomas

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Abstract

Nitric oxide (NO) is a novel gaseous intercellular transmitter thought to play important physiological roles in the regulation of blood flow and hormone secretion in, for example, the pituitary, the thyroid, and the endocrine pancreas. Whether nitric oxide synthase (NOS) is present in the human parathyroid glands has not yet been demonstrated. In the present study, histologically normal, but functionally suppressed human parathyroid glands and parathyroid adenomas from patients with primary hyperparathyroidism were investigated by immunocytochemistry with antibodies against neuronal NOS and by reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry. We also used H&E to identify the NOS-immunoreactive cells. Immunocytochemistry demonstrated the presence of neuronal-type NOS in a subpopulation of glandular cells, identified as oxyphilic cells, in both normal parathyroid glands and adenomas. NADPH-diaphorase staining visualized NOS in the endothelium of blood vessels and in glandular cells, corresponding to those containing immunoreactive NOS. In addition, we found NADPH-diaphorase staining in many chief cells. Our results indicate that both glandular cells and vascular endothelium in human parathyroid glands and adenomas express NOS. There is thus a morphological substrate for locally produced NO that may be involved in the regulation of parathyroid blood flow and hormone secretion.

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References

  1. Moncada S. Thel-arginine: nitric oxide pathway. Acta Physiol Scand 145:201–227, 1992.

    Article  PubMed  CAS  Google Scholar 

  2. Nathan C, Qiao-Wen Xie. Nitric oxide synthases: roles, tools and controls. Cell 78:915–918, 1994.

    Article  PubMed  CAS  Google Scholar 

  3. Schmidt H, Walter U. NO at work. Cell 78:919–925, 1994.

    Article  PubMed  CAS  Google Scholar 

  4. Snyder SH, Bredt DS. Nitric oxide as a neuronal messenger. Trends Pharmacol Sci 12:125–128, 1991.

    Article  PubMed  CAS  Google Scholar 

  5. Förstermann U, Schmidt HHHW, Pollock JS, Sheng H, Mitchell JA, Warner TD, Nakane M, Murad F. Isoforms of nitric oxide synthase. Characterization and purification from different cell types. Biochem Pharmacol 42:1849–1857, 1991.

    Article  PubMed  Google Scholar 

  6. Ali Syed M, Leong S-K, Chan AS. Localization of NADPH-diaphorase reactivity in the chicken and mouse thyroid gland. Thyroid 4:475–478, 1994.

    Google Scholar 

  7. Dawson TM, Bredt DS, Fotuhi M, Hwang PM, Snyder SH. Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc Natl Acad Sci USA 88:7797–7891, 1991.

    Article  PubMed  CAS  Google Scholar 

  8. Ekblad E, Alm P, Sundler F. Distribution, origin and projections of nitric oxide synthase-containing neurons in gut and pancreas. Neuroscience 63:233–248, 1994.

    Article  PubMed  CAS  Google Scholar 

  9. Ekblad E, Mulder H, Uddman R, Sundler F. NOS-containing neurons in the rat gut and coeliac ganglia. Neuropharmacology 33: 1323–1331, 1994.

    Article  PubMed  CAS  Google Scholar 

  10. Hope BT, Michael GJ, Knigge KM, Vincent SR. Neuronal NADPH-diaphorase is a nitric oxide synthase. Proc Natl Acad Sci USA 88:2811–2814, 1991.

    Article  PubMed  CAS  Google Scholar 

  11. Lloyd RV, Jin L, Qian X, Zhang S, Scheithauer BW. Nitric oxide synthase in the human pituitary gland. Am J Pathol 146:86–94, 1995.

    PubMed  CAS  Google Scholar 

  12. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J 6:3051–3064, 1992.

    PubMed  CAS  Google Scholar 

  13. Schmidt HHHW, Gagne GG, Nakane M, Pollock JS, Miller MF, Murad P. Mapping of neuronal nitric oxide synthase in the rat suggest frequent co-localization with NADPH diaphorase but not with soluble guanylyl cyclase and novel paraneuronal functions for nitrinergic signal transduction. J Histochem Cytochem 40:1439–1456, 1992.

    PubMed  CAS  Google Scholar 

  14. Schmidt HHHW, Warner TD, Ishii K, Sheng H, Murad F. Insulin secretion from pancreatic B cells caused byl-arginine-derived nitrogen oxides. Science 255:721–723, 1992.

    Article  PubMed  CAS  Google Scholar 

  15. Wörl J, Wiesand M, Mayer B, Greskötter K-R, Neuhuber WL. Neuronal and endothelial nitric oxide synthase immunoreactivity and NADPH-diaphorase staining in rat and human pancreas: influence of fixation. Histochemistry 102:353–364, 1994.

    Article  PubMed  Google Scholar 

  16. Afework M, Tomlinson A, Belai A, Burnstock G. Colocalization of nitric oxide synthase and NADPH-diaphorase in rat adrenal gland. Neurochemistry 3:893–896, 1992.

    CAS  Google Scholar 

  17. Alm P, Larsson B, Ekblad E, Sundler F, Andersson K-E. Immunohistochemical localization of peripheral nitric oxide synthase-containing nerves using antibodies raised against synthesized C- and N-terminal fragments of cloned enzyme from rat brain. Acta Physiol Scand 148:421–429, 1993.

    PubMed  CAS  Google Scholar 

  18. Dun NJ, Dun SL, Wu SY, Förstermann V. Nitric oxide synthase immunoreactivity in rat superior cervical ganglia and adrenal glands. Neurosci Lett 158:51–54, 1993.

    Article  PubMed  CAS  Google Scholar 

  19. Ceccatelli S, Hulting A-L, Zhang X, Gustafsson L, Villar M, Hökfelt T. Nitric oxide synthase in the rat anterior pituitary gland and the role of nitric oxide in regulation of luteinizing hormone secretion. Proc Natl Acad Sci USA 90:11,292–11,296, 1993.

    Article  CAS  Google Scholar 

  20. Hökfelt T, Ceccatelli S, Gustafsson L, Hulting AL, Verge V, Villar M, Xu X-J, Xu ZQ, Wiesenfeld-Hallin Z, Zhang X. Plasticity of NO synthase expression in the nervous and endocrine systems. Neuropharmacology 33:1221–1227, 1994.

    Article  PubMed  Google Scholar 

  21. Panagiotidis G, Alm P, Lundquist I. Inhibition of islet nitric oxide synthase increases arginine-induced insulin release. Eur J Pharmacol 229:277, 278, 1992.

    Article  PubMed  CAS  Google Scholar 

  22. Eizirik DL, Leijerstam F. The inducible form of nitric oxide synthase (iNOS) in insulin-producing cells. Diabetes Metab 20:116–122, 1994.

    CAS  Google Scholar 

  23. Mundel P, Bachmann S, Bader M, Fischer A, Kummer W, Mayer B, Kriz W. Expression of nitric oxide synthase in kidney macula densa cells. Kidney Int 42:1017–1019, 1992.

    Article  PubMed  CAS  Google Scholar 

  24. Thorup PC, Sundler F, Ekblad E, Persson AEG. Resetting of the tubuloglomerular feedback mechanism by blockade of NO-synthase. Acta Physiol Scand 148:359–360, 1993.

    PubMed  CAS  Google Scholar 

  25. Wilcox CS, Welch WJ, Murad F, Gross SS, Taylor G, Levi R, Schmidt HHHW. Nitric oxide synthase in macula densa regulates glomerular capillary pressure. Proc Natl Acad Sci USA 89:11,993–11,997, 1992.

    CAS  Google Scholar 

  26. Esteves RZ, Van Sande J, Dumant JE. Nitric oxide as a signal in thyroid. Mol Cell Endocrinol 90:R1-R3, 1992.

    Article  PubMed  CAS  Google Scholar 

  27. Jones PM, Persaud SJ, Bjaaland T, Pearson JD, Howell SL. Nitric oxide is not involved in the initiation of insulin secretion from rat islets of Langerhans. Diabetologia 35:1020–1027, 1992.

    Article  PubMed  CAS  Google Scholar 

  28. Vincent SR, Schmidt HHHW, Warner TD, Ishii K, Sheng H, Murad F. Nitric oxide and arginine-evoked insulin secretion. Science 258:1376–1378, 1992.

    Article  PubMed  CAS  Google Scholar 

  29. Grimelius L, Åkerström G, Johansson H, Bergström R. Anatomy and histopathology of human parathyroid glands. In: Sommers SC, Rosen PP, eds. Pathology annual, vol. 16. Norwalk, CT: Appleton-Centory-Crofts. 1981; 1–24.

    Google Scholar 

  30. Grimelius L, Åkerström G, Bondesson L, Juhlin C, Johansson H, Ljunghall S, Rastad J. The role of the pathologist in diagnosis and surgical decision making in hyperparathyroidism. World J Surg 15: 698–705, 1991.

    Article  PubMed  CAS  Google Scholar 

  31. Bergenfelz A, Nordén N-E, Ahrén B. Intraoperative fall of plasma levels of intact parathyroid hormone after removal of one enlarged parathyroid gland in hyperparathyroid patients. Eur J Surg 157:109–112, 1991.

    PubMed  CAS  Google Scholar 

  32. Hope BT, Vincent SR. Histochemical characterization of neuronal NADPH-diaphorase. J Histochem Cytochem 37:653–661, 1989.

    PubMed  CAS  Google Scholar 

  33. Luts L, Bergenfelz A, Alumets J, Sundler F. Peptide-containing nerve fibers in normal human parathyroid glands and in human parathyroid adenomas. Eur J Endocrinol 133:543–551, 1995.

    PubMed  CAS  Google Scholar 

  34. Brown EM. Four-parameter model of sigmoidal relationship between parathyroid hormone release and extracellular calcium concentration in normal and abnormal parathyroid tissue. J. Clin. Endocrinol Metab 56:572–581, 1983.

    PubMed  CAS  Google Scholar 

  35. Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O, Sun A, Hediger MA, Lytton J, Hebert SC. Cloning and characterization of an extracellular Ca2+-sensing receptor from bovine parathyroid. Nature 366: 575–580, 1993.

    Article  PubMed  CAS  Google Scholar 

  36. Brown EM, Pollak M, Hebert SC. Molecular mechanism underlying the sensing of extracellular Ca2+ by parathyroid and kidney cells. Eur J Endocr 132:523–531, 1995.

    CAS  Google Scholar 

  37. Brown EM, Chen CJ, Kifor O, Leboff MS, El-Hajj G, Fajtova V, Rubin LT. Ca2+-sensing, second messengers and the control of parathyroid hormone secretion. Cell Calcium 11:333–337, 1990.

    Article  PubMed  CAS  Google Scholar 

  38. Pocotte SL, Ehrenstein G, Fitzpatrick LA. Regulation of parathyroid hormone secretion. Endocrine Rev 12:291–301, 1991.

    CAS  Google Scholar 

  39. Luts L, Sundler F: Peptide-containing nerve fibers in the parathyroid glands of different species. Regul Pept 50:147–158, 1994.

    Article  PubMed  CAS  Google Scholar 

  40. Drees BM, Rouse J, Johnson J, Hamilton JW. Bovine parathyroid glands secrete a 26-kDa N-terminal fragment of chromogranin-A which inhibits parathyroid cell secretion. Endocrinology 129:3381–3387, 1991.

    Article  PubMed  CAS  Google Scholar 

  41. Fasciotto BH, Gorr S-U, Bourdeau AM, Cohn DV. Autocrine regulation of parathyroid secretion: inhibition of secretion by chromogranin-A (secretory protein-1) and potentiation of secretion by chromogranin-A and pancreastatin antibodies. Endocrinology 127:1329–1335, 1990.

    PubMed  CAS  Google Scholar 

  42. Fujii Y, Moreira JE, Orlando C, Maggi M, Aurbach GD, Brandi ML, Sakaguchi K. Endothelin as an autocrine factor in the regulation of parathyroid cells. Proc Natl Acad Sci USA 88:4235–4239, 1991.

    Article  PubMed  CAS  Google Scholar 

  43. Tanini A, Failli P, Maggi M, Franceschelli F, Frediani U, Becherin L, Giotti A, Ruocco C, Brandi ML. Effects of endothelin-1 on bovine parathyroid cells. Biochem Biophys Res Commun 193:59–66, 1993.

    Article  PubMed  CAS  Google Scholar 

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Luts, L., Bergenfelz, A., Alumets, J. et al. Nitric oxide synthase in human parathyroid glands and parathyroid adenomas. Endocr Pathol 7, 207–213 (1996). https://doi.org/10.1007/BF02739923

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