Osteoporosis International

, Volume 21, Issue 9, pp 1609–1616 | Cite as

Daidzein administration positively affects thyroid C cells and bone structure in orchidectomized middle-aged rats

  • B. Filipović
  • B. Šošić-Jurjević
  • V. Ajdžanović
  • D. Brkić
  • M. Manojlović-Stojanoski
  • V. Milošević
  • M. Sekulić
Original Article

Abstract

Summary

Thyroid C cells hormone, calcitonine, inhibits bone resorption. We have demonstrated that daidzein treatment of orchidectomized rats (model for osteoporosis) stimulated C cells and increased trabecular bone mass. These results suggest that, besides direct action, daidzein may also affect bone structure indirectly through enhancement of thyroid C cell activity.

Introduction

Thyroid C cells produce calcitonin (CT) which acts as an inhibitor of bone resorption. In this study, the influence of daidzein treatment on thyroid C cells, bone structure, and bone function in orchidectomized (Orx) middle-aged rats was investigated.

Methods

Sixteen-month-old Wistar rats were divided into Orx and sham-operated (SO) groups. Half the Orx rats were given subcutaneous injections of daidzein (30 mg/kg b.w./day) for 3 weeks. CT-immunopositive thyroid C cells were morphometrically analyzed. The metaphyseal region of the proximal tibia was measured histomorphometrically, and cancellous bone area (B.Ar), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp) were calculated. Serum samples were analyzed for CT and osteocalcin (OC), calcium (Ca) and phosphorus concentrations, and urine samples for Ca levels.

Results

Treatment of Orx animals with daidzein significantly increased volume of C cells compared to the Orx rats. Daidzein also enhanced B.Ar, Tb.Th, and Tb.N and reduced Tb.Sp. The serum OC and urinary Ca concentrations decreased significantly in comparison with the Orx group.

Conclusions

These findings indicate that daidzein treatment stimulates thyroid C cells, increase trabecular bone mass, and decrease bone turnover in Orx middle-aged rats, which is the model of male osteoporosis.

Keywords

Bone Daidzein Histomorphometry Immunohistochemistry Rats Thyroid C cells 

Notes

Acknowledgments

This work was supported by the Ministry for Science of Serbia, grant number 143007B. The authors wish to express their gratitude to Dr. Anna Nikolić, Ph.D. for language correction of the manuscript.

Conflicts of interest

None.

References

  1. 1.
    Siddiqui NA, Shetty KR, Duthie EH Jr (1999) Osteoporosis in older men: discovering when and how to treat it. Geriatrics 54:20–22 27-28, 30 passimPubMedGoogle Scholar
  2. 2.
    Vanderschueren D, Boonen S, Bouillon R (1998) Action of androgens versus estrogens in male skeletal homeostasis. Bone 23:391–394CrossRefPubMedGoogle Scholar
  3. 3.
    Khosla S, Melton LJ 3rd, Atkinson EJ, O’Fallon WM, Klee GG, Riggs BL (1998) Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. J Clin Endocrinol Metab 83:2266–2274CrossRefPubMedGoogle Scholar
  4. 4.
    Greendale GA, Edelstein S, Barrett-Connor E (1997) Endogenous sex steroids and bone mineral density in older women and men: the Rancho Bernardo Study. J Bone Miner Res 12:1833–1843CrossRefPubMedGoogle Scholar
  5. 5.
    Slemenda CW, Longcope C, Zhou L, Hui SL, Peacock M, Johnston CC (1997) Sex steroids and bone mass in older men. Positive associations with serum estrogens and negative associations with androgens. J Clin Invest 100:1755–1759CrossRefPubMedGoogle Scholar
  6. 6.
    Falahati-Nini A, Riggs BL, Atkinson EJ, O’Fallon WM, Eastell R, Khosla S (2000) Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J Clin Invest 106:1553–1560CrossRefPubMedGoogle Scholar
  7. 7.
    Hoff AO, Gagel RF (2005) Osteoporosis in breast and prostate cancer survivors. Oncology 19:651–658PubMedGoogle Scholar
  8. 8.
    Vanderschueren D, Van Herck E, Suiker AMH, Visser WJ, Schot LPC, Bouillon R (1992) Bone and mineral metabolism in aged male rats: short- and long-term effects of androgen deficiency. Endocrinology 130:2906–2916CrossRefPubMedGoogle Scholar
  9. 9.
    Ornoy A, Giron S, Aner R, Goldstein M, Boyan BD, Schwartz Z (1994) Gender dependent effects of testosterone and 17 beta-estradiol on bone growth and modelling in young mice. Bone Miner 24:43–58CrossRefPubMedGoogle Scholar
  10. 10.
    Tuukkanen J, Peng Z, Väänänen HK (1994) Effect of running exercise on the bone loss induced by orchidectomy in the rat. Calcif Tissue Int 55:33–37CrossRefPubMedGoogle Scholar
  11. 11.
    Filipović B, Šošić-Jurjević B, Ajdžanović V, Trifunović S, Mč M-S, Ristić N, Nestorović N, Milošević V, Sekulić M (2007) The effect of orchidectomy on thyroid C cells and bone histomorphometry in middle-aged rats. Histochem Cell Biol 128:153–159CrossRefPubMedGoogle Scholar
  12. 12.
    Chambers TJ, Magnus CJ (1982) Calcitonin alters behaviour of isolated osteoclasts. J Pathol 136:27–39CrossRefPubMedGoogle Scholar
  13. 13.
    Vandenput L, Boonen S, Van Herck E, Swinnen JV, Bouillon R, Vanderschueren D (2002) Evidence from the aged orchidectomized male rat model that 17beta-estradiol is a more effective bone-sparing and anabolic agent than 5alpha-dihydrotestosterone. J Bone Miner Res 17:2080–2086CrossRefPubMedGoogle Scholar
  14. 14.
    Setchell KD (2001) Soy isoflavones--benefits and risks from nature’s selective estrogen receptor modulators (SERMs). J Am Coll Nutr 20:354S–362S discussion 381S-383SPubMedGoogle Scholar
  15. 15.
    Anderson JJ, Anthony M, Messina M, Garne SC (1999) Effects of phyto-oestrogens on tissues. Nutr Res Rev 12:75–116CrossRefPubMedGoogle Scholar
  16. 16.
    Strom SS, Yamamura Y, Duphorne CM, Spitz MR, Babaian RJ, Pillow PC, Hursting SD (1999) Phytoestrogen intake and prostate cancer: a case-control study using a new database. Nutr Cancer 33:20–25CrossRefPubMedGoogle Scholar
  17. 17.
    Chrzan BG, Bradford PG (2007) Phytoestrogens activate estrogen receptor b1 and strogenic responses in human breast and bone cancer cell lines. Mol Nutr Food Res 51:171–177CrossRefPubMedGoogle Scholar
  18. 18.
    Krazeisen A, Breitling R, Möller G, Adamski J (2001) Phytoestrogens inhibit human 17β-hydroxysteroid dehydrogenase type 5. Mol Cell Endocrinol 171:151–162CrossRefPubMedGoogle Scholar
  19. 19.
    Khalil DA, Lucas EA, Smith BJ, Soung DY, Devareddy L, Juma S, Akhter MP, Recker R, Arjmandi BH (2005) Soy isoflavones may protect against orchidectomy-induced bone loss in aged male rats. Calcif Tissue Int 76:56–62CrossRefPubMedGoogle Scholar
  20. 20.
    Soung DY, Devareddy L, Khalil DA, Hooshmand S, Patade A, Lucas EA, Arjmandi BH (2006) Soy affects trabecular microarchitecture and favorably alters select bone-specific gene expressions in a male rat model of osteoporosis. Calcif Tissue Int 78:385–391CrossRefPubMedGoogle Scholar
  21. 21.
    Gao YH, Yamaguchi M (1999) Suppressive effect of genistein on rat bone osteoclasts: apoptosis is induced through Ca2+ signaling. Biol Pharm Bull 22:805–809PubMedGoogle Scholar
  22. 22.
    Rassi CM, Lieberherr M, Chaumaz G, Pointillart A, Cournot G (2002) Down-regulation of osteoclast differentiation by daidzein via caspase 3. J Bone Miner Res 17:630–638CrossRefPubMedGoogle Scholar
  23. 23.
    Dang Z, Löwik CW (2004) The balance between concurrent activation of ERs and PPARs determines daidzein-induced osteogenesis and adipogenesis. J Bone Miner Res 19:853–861CrossRefPubMedGoogle Scholar
  24. 24.
    Watanabe K, Takekoshi S, Kakudo K (1992) Effects of ipriflavone on calcitonin synthesis in C cells of the rat thyroid. Calcif Tissue Int 51:S27–S29CrossRefPubMedGoogle Scholar
  25. 25.
    Picherit C, Coxam V, Bennetau-Pelissero C, Kati-Coulibaly S, Davicco MJ, Lebeque P, Barlet JP (2000) Daidzein is more efficient than genistein in preventing ovariectomy­induced bone loss in rats. J Nutr 130:1675–1681PubMedGoogle Scholar
  26. 26.
    Sternberger LA, Hardy PH Jr, Cuculis JJ, Mayer HG (1970) The unlabeled antibody enzyme method of immunohistochemistry. Preparation and properties of soluble antigen–antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem 18:315–333PubMedGoogle Scholar
  27. 27.
    Sekulić M, Lovren M, Milošević V, Mićić M, Balint-Perić LJ (1998) Thyroid C cells of middle-aged rats treated with estradiol or calcium. Histochem Cell Biol 109:257–262CrossRefPubMedGoogle Scholar
  28. 28.
    Weibel ER (1979) Practical methods for biological morphometry. Stereological methods, vol 1. Academic, London, pp 1–415Google Scholar
  29. 29.
    Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJH, Ott SM, Recker RR (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. J Bone Miner Res 2:595–610CrossRefPubMedGoogle Scholar
  30. 30.
    Evans G, Bryant HU, Magee D, Sato M, Turner RT (1994) The effects of raloxifene on tibia histomorphometry in ovariectomized rats. Endocrinology 134:2283–2288CrossRefPubMedGoogle Scholar
  31. 31.
    Parfitt AM, Matthews CHE, Villanueva AR, Kleerekoper M, Frame B, Rao DS (1983) Relationship between surface, volume and thickness of iliac trabecular bone in again and in osteoporosis. Implications for the microanatomic and cellular mechanisms of bone loss. J Clin Invest 72:1396–1409CrossRefPubMedGoogle Scholar
  32. 32.
    Chappard D, Legrand E, Pascaretti C, Basle MF, Audran M (1999) Comparison of eighr histomorphometric methods for measuring trabecular bone architecture by image analysis on histological sections. Microsc Res Tech 45:303–312CrossRefPubMedGoogle Scholar
  33. 33.
    Weiner KX, Dias JA (1990) Protein synthesis is required for testosterone to decrease ornithine decarboxylase messenger RNA levels in rat Sertoli cells. Mol Endocrinol 4:1791–1798CrossRefPubMedGoogle Scholar
  34. 34.
    Naveh-Many T, Almogi G, Livni N, Silver J (1992) Estrogen receptors and biologic response in rat parathyroid tissue and C cells. J Clin Invest 90:2434–2438CrossRefPubMedGoogle Scholar
  35. 35.
    Blechet C, Lecomte P, De Calan L, Beutter P, Guyetant S (2007) Expression of sex steroid hormone receptors in C cell hyperplasia and medullary thyroid carcinoma. Virchows Arch 450:433–439CrossRefPubMedGoogle Scholar
  36. 36.
    Zhai QH, Ruebel K, Thompson GB, Lloyd RV (2003) Androgen receptor expression in C-cells and in medullary thyroid carcinoma. Endocr Pathol 14:159–165CrossRefPubMedGoogle Scholar
  37. 37.
    Filipović B, Šošić-Jurjević B, Nestorović N, Manojlović-Stojanoski M, Kostić N, Milošević V, Sekulić M (2003) The thyroid C cells of ovariectomized rats treated with estradiol. Histochem Cell Biol 120:409–414CrossRefPubMedGoogle Scholar
  38. 38.
    Takeuchi S, Takahashi T, Sawada Y, Iida M, Matsuda T, Kojima H (2009) Comparative study on the nuclear hormone receptor activity of various phytochemicals and their metabolites by reporter gene assays using Chinese hamster ovary cells. Biol Pharm Bull 32:195–202CrossRefPubMedGoogle Scholar
  39. 39.
    Ishimi Y, Yoshida M, Wakimoto S, Wu J, Chiba H, Wang X, Takeda K, Miyaura C (2002) Genistein, a soybean isoflavone, affects bone marrow lymphopoiesis and prevents bone loss in castrated male mice. Bone 31:180–185CrossRefPubMedGoogle Scholar
  40. 40.
    Nicholson CG, Mosley JM, Sexton PM, Mendelsohn FAO, Martin TJ (1986) Abundant calcitonin receptors in isolated rat osteoclasts. J Clin Invest 78:355–360CrossRefPubMedGoogle Scholar
  41. 41.
    Zaidi M, Datta HK, Moonga BS, MacIntyre I (1990) Evidence that the action of calcitonin on rat osteoclasts is mediated by two G proteins acting via separate post-receptor pathways. J Endocrinol 126:473–481CrossRefPubMedGoogle Scholar
  42. 42.
    Hunter SJ, Schraer H, Gay CV (1989) Characterization of the cytoskeleton of isolated chick osteoclasts: effect of calcitonin. J Histochem Cytochem 37:1529–1537PubMedGoogle Scholar
  43. 43.
    Farley J, Dimai HP, Stilt-Coffing B, Farley P, Pham T, Mohan S (2000) Calcitonin increases the concentration of insulin-like growth factors in serum-free cultures of human osteoblast-line cells. Calcif Tissue Int 67:247–254CrossRefPubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2009

Authors and Affiliations

  • B. Filipović
    • 1
    • 3
  • B. Šošić-Jurjević
    • 1
  • V. Ajdžanović
    • 1
  • D. Brkić
    • 2
  • M. Manojlović-Stojanoski
    • 1
  • V. Milošević
    • 1
  • M. Sekulić
    • 1
  1. 1.Institute for Biological ResearchBelgradeSerbia
  2. 2.Johnson and Johnson S.E. Inc.BelgradeSerbia
  3. 3.Institute for Biological ResearchBelgradeSerbia

Personalised recommendations