Skip to main content

Advertisement

SpringerLink
Log in

Inositol(s) in thyroid function, growth and autoimmunity

  • Published:
Reviews in Endocrine and Metabolic Disorders Aims and scope Submit manuscript

Abstract

Myo-inositol and phosphatidylinositol(s) play a pivotal function in many metabolic pathways that, if impaired, impact unfavorably on human health. This review analyzes several experimental and clinical investigations regarding the involvement of this class of molecules in physiological and pathological situations, with a major focus on thyroid. Central issues are the relationship between phosphatidylinositol and thyrotropin (TSH) signaling on one hand, and phosphatydylinositol and autoimmunity on the other hand. Other issues are the consequences of malfunction of some receptors, such as those ones for TSH (TSHR), insulin (IR) and insulin-like growth factor-1 (IGF-1R), or the connection between serum TSH concentrations and insulin resistance. Also covered are insulin resistance, metabolic syndrome and their allied disorders (diabetes, polycystic ovary syndrome [PCOS]), autoimmunity and certain malignancies, with their reciprocal links. Myoinositol has promising therapeutic potential. Appreciation of the inositol pathways involved in certain disorders, as mentioned in this review, may stimulate researchers to envisage additional therapeutic applications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Murthy PP. Structure and nomenclature of inositol phosphates, Phosphoinositides, and Glycosylphosphatidylinositols. Subcell Biochem. 2006;39:1–19.

    Article  PubMed  Google Scholar 

  2. Kompanje EJ, Jansen TC, van der Hoven B, Bakker J. The first demonstration of lactic acid in human blood in shock by Johann Joseph Scherer (1814-1869) in January 1843. Intensive Care Med. 2007;33:1967–1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Buttner J. Johann Joseph von Scherer (1814-69). The early history of clinical chemistry. J Clin Chem Clin Biochem. 1978;16:478–83.

    CAS  PubMed  Google Scholar 

  4. Hartig T. Über das Klebermehl Botanische Zeitung. 1855;13:881–2.

    Google Scholar 

  5. Clements Jr RS, Darnell B. Myo-inositol content of common foods: development of a high-myo-inositol diet. Am J Clin Nutr. 1980;33:1954–67.

    CAS  PubMed  Google Scholar 

  6. Hooper NM. Glycosyl-phosphatidylinositol anchored membrane enzymes. Clin Chim Acta. 1997;266:3–12.

    Article  CAS  PubMed  Google Scholar 

  7. Di Paolo G, De Camilli P. Phosphoinositides in cell regulation and membrane dynamics. Nature. 2006;443:651–7.

    Article  PubMed  Google Scholar 

  8. Berridge MJ. Inositol trisphosphate and diacylglycerol as second messengers. Biochem J. 1984;220:345–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Downes CP. Twenty-fifth Colworth medal lecture. The cellular functions of myo-inositol. Biochem Soc Trans. 1989;17:259–68.

    Article  CAS  PubMed  Google Scholar 

  10. Downes CP, Macphee CH. Myo-inositol metabolites as cellular signals. Eur J Biochem. 1990;193:1–18.

    Article  CAS  PubMed  Google Scholar 

  11. Kopp P. Thyroid hormone synthesis. In: Braverman LE, Cooper DS, editors. Werner and Ingbar’s The Thyroid: a fundamental and clinical text. Philadelphia: Wolters Kluwer Lippincott Williams & Wilkins, 10th edition, 2013. pp. 48–74.

  12. Corvilain B, Laurent E, Lecomte M, Vansande J, Dumont JE. Role of the cyclic adenosine 3′,5′-monophosphate and the phosphatidylinositol-Ca2+ cascades in mediating the effects of thyrotropin and iodide on hormone synthesis and secretion in human thyroid slices. J Clin Endocrinol Metab. 1994;79:152–9.

    CAS  PubMed  Google Scholar 

  13. Song Y, Driessens N, Costa M, De Deken X, Detours V, Corvilain B, Maenhaut C, Miot F, Van Sande J, Many MC, Dumont JE. Roles of hydrogen peroxide in thyroid physiology and disease. J Clin Endocrinol Metab. 2007;92:3764–73.

    Article  CAS  PubMed  Google Scholar 

  14. Grasberger H, Van Sande J, Hag-Dahood Mahameed A, Tenenbaum-Rakover Y, Refetoff S. Brief report: a familial thyrotropin (TSH) receptor mutation provides in vivo evidence that the inositol phosphates/Ca2+ cascade mediates TSH action on thyroid hormone synthesis. J Clin Endocrinol Metab. 2007;92:2816–20.

  15. Field JB, Ealey PA, Marshall NJ, Cockcroft S. Thyroid-stimulating hormone stimulates increases in inositol phosphates as well as cyclic AMP in the FRTL-5 rat thyroid cell line. Biochem J. 1987;247:519–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. de Oliveira M, Luvizotto Rde A, Olimpio RM, De Sibio MT, Conde SJ. Biz Rodrigues Silva C, Moretto FC, Nogueira CR. Triiodothyronine increases mRNA and protein leptin levels in short time in 3 T3-L1 adipocytes by PI3K pathway activation. PLoS ONE. 2013;8:e74856.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Spaulding SW. Biological actions of thyrotropin. In: Braverman LE, Cooper DS, editors. Werner and Ingbar’s The Thyroid: a fundamental and clinical text. Philadelphia: Wolters Kluwer Lippincott Williams & Wilkins, 10th edition, 2013. pp. 183–97.

  18. Ruggeri RM, Vitarelli E, Barresi G, Trimarchi F, Benvenga S, Trovato M. The tyrosine kinase receptor c-met, its cognate ligand HGF and the tyrosine kinase receptor trasducers STAT3, PI3K and RHO in thyroid nodules associated with Hashimoto’s thyroiditis: an immunohistochemical characterization. Eur J Histochem. 2010;54:e24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ruggeri RM, Vitarelli E, Barresi G, Trimarchi F, Benvenga S, Trovato M. HGF/C-MET system pathways in benign and malignant histotypes of thyroid nodules: an immunohistochemical characterization. Histol Histopathol. 2012;27:113–21.

    CAS  PubMed  Google Scholar 

  20. Sarlis NJ, Benvenga S. Molecular signaling in thyroid cancer. Cancer Treat Res. 2004;122:237–64.

    Article  PubMed  Google Scholar 

  21. Benvenga S. Update on thyroid cancer. Horm Metab Res. 2008;40:323–8.

    Article  CAS  PubMed  Google Scholar 

  22. Ciampolillo A, De Tullio C, Giorgino F. The IGF-I/IGF-I receptor pathway: implications in the pathophysiology of thyroid cancer. Curr Med Chem. 2005;12:2881–91.

    Article  CAS  PubMed  Google Scholar 

  23. Maiorano E, Ciampolillo A, Viale G, Maisonneuve P, Ambrosi A, Triggiani V, Marra E, Perlino E. Insulin-like growth factor 1 expression in thyroid tumors. Appl Immunohistochem Mol Morphol. 2000;8:110–9.

    CAS  PubMed  Google Scholar 

  24. Malaguarnera R, Frasca F, Garozzo A, Gianì F, Pandini G, Vella V, Vigneri R, Belfiore A. Insulin receptor isoforms and insulin-like growth factor receptor in human follicular cell precursors from papillary thyroid cancer and normal thyroid. J Clin Endocrinol Metab. 2011;96:766–74.

    Article  CAS  PubMed  Google Scholar 

  25. Poulaki V, Mitsiades CS, McMullan C, Sykoutri D, Fanourakis G, Kotoula V, Tseleni-Balafouta S, Koutras DA, Mitsiades N. Regulation of vascular endothelial growth factor expression by insulin-like growth factor I in thyroid carcinomas. J Clin Endocrinol Metab. 2003;88:5392–8.

    Article  CAS  PubMed  Google Scholar 

  26. Belfiore A, Malaguarnera R. Insulin receptor and cancer. Endocr Relat Cancer. 2011;18:R125–47.

    Article  CAS  PubMed  Google Scholar 

  27. Ben-Shmuel S, Rostoker R, Scheinman EJ, LeRoith D. Metabolic syndrome, type 2 diabetes, and cancer: epidemiology and potential mechanisms. Handb Exp Pharmacol. 2016;233:355–72.

    Article  PubMed  Google Scholar 

  28. Hanefeld M, Pistrosch F, Bornstein SR, Birkenfeld AL. The metabolic vascular syndrome - guide to an individualized treatment. Rev Endocr Metab Disord. 2016;17:5–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Rezzonico J, Rezzonico M, Pusiol E, Pitoia F, Niepomniszcze H. Introducing the thyroid gland as another victim of the insulin resistance syndrome. Thyroid. 2008;18:461–4.

    Article  CAS  PubMed  Google Scholar 

  30. Rezzonico J, Rezzonico M, Pusiol E, Pitoia F, Niepomniszcze H. Metformin treatment for small benign thyroid nodules in patients with insulin resistance. Metab Syndr Relat Disord. 2011;9:69–75.

    Article  CAS  PubMed  Google Scholar 

  31. Rezzonico JN, Rezzonico M, Pusiol E, Pitoia F, Niepomniszcze H. Increased prevalence of insulin resistance in patients with differentiated thyroid carcinoma. Metab Syndr Relat Disord. 2009;7:375–80.

    Article  CAS  PubMed  Google Scholar 

  32. Yasar HY, Ertuğrul O, Ertuğrul B, Ertuğrul D, Sahin M. Insulin resistance in nodular thyroid disease. Endocr Res. 2011;36:167–74.

    Article  CAS  PubMed  Google Scholar 

  33. Chen G, Xu S, Renko K, Derwahl M. Metformin inhibits growth of thyroid carcinoma cells, suppresses self-renewal of derived cancer stem cells, and potentiates the effect of chemotherapeutic agents. J Clin Endocrinol Metab. 2012;97:E510–20.

    Article  CAS  PubMed  Google Scholar 

  34. Oh JY, Sung YA, Lee HJ. Elevated thyroid stimulating hormone levels are associated with metabolic syndrome in euthyroid young women. Korean J Intern Med. 2013;28:180–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Park HT, Cho GJ, Ahn KH, Shin JH, Hong SC, Kim T, Hur JY, Kim YT, Lee KW, Kim SH. Thyroid stimulating hormone is associated with metabolic syndrome in euthyroid postmenopausal women. Maturitas. 2009;62:301–5.

    Article  CAS  PubMed  Google Scholar 

  36. Garduño-Garcia Jde J, Alvirde-Garcia U, López-Carrasco G, Padilla Mendoza ME, Mehta R, Arellano-Campos O, Choza R, Sauque L, Garay-Sevilla ME, Malacara JM, Gomez-Perez FJ, Aguilar-Salinas CA. TSH and free thyroxine concentrations are associated with differing metabolic markers in euthyroid subjects. Eur J Endocrinol. 2010;163:273–8.

    Article  PubMed  Google Scholar 

  37. Roos A, Bakker SJ, Links TP, Gans RO, Wolffenbuttel BH. Thyroid function is associated with components of the metabolic syndrome in euthyroid subjects. J Clin Endocrinol Metab. 2007;92:491–6.

    Article  CAS  PubMed  Google Scholar 

  38. Lin SY, Wang WY, Liu PH, Lai WA, Sheu WH. Lower serum free thyroxine levels are associated with the metabolic syndrome. Metabolism. 2005;54:1524–8.

    Article  CAS  PubMed  Google Scholar 

  39. Uzunlulu M, Yorulmaz E, Oguz A. Prevalence of subclinical hypothyroidism in patients with metabolic syndrome. Endocr J. 2007;54:71–6.

    Article  CAS  PubMed  Google Scholar 

  40. Shantha GP, Kumar AA, Jeyachandran V, Rajamanickam D, Rajkumar K, Salim S, Subramanian KK, Natesan S. Association between primary hypothyroidism and metabolic syndrome and the role of C reactive protein: a cross-sectional study from South India. Thyroid Res. 2009;2:2.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Giandalia A, Russo GT, Romeo EL, Alibrandi A, Villari P, Mirto AA, Armentano G, Benvenga S, Cucinotta D. Influence of high-normal serum TSH levels on major cardiovascular risk factors and visceral adiposity index in euthyroid type 2 diabetic subjects. Endocrine. 2014;47:152–60.

    Article  CAS  PubMed  Google Scholar 

  42. El-Eshmawy MM, Abd El-Hafez HA, El Shabrawy WO, Abdel Aal IA. Subclinical hypothyroidism is independently associated with microalbuminuria in a cohort of prediabetic Egyptian adults. Diabetes Metab J. 2013;37:450–7.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Al Sayed A, Al Ali N, Bo Abbas Y, Alfadhli E. Subclinical hypothyroidism is associated with early insulin resistance in Kuwaiti women. Endocr J. 2006;53:653–7.

    Article  PubMed  Google Scholar 

  44. Billic-Komarica E, Becirag A, Junuzovic D. The importance of HBA1c control in patients with subclinical hypothyroidism. Mater Sociomed. 2012;24:212–9.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Wang C. The relationship between type 2 diabetes mellitus and related thyroid diseases. J Diabetes Res. 2013;2013:390534.

    PubMed  PubMed Central  Google Scholar 

  46. Brenta G. Why can insulin resistance be a natural consequence of thyroid dysfunction? J Thyroid Res. 2011;2011:152850.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Chidakel A, Mentuccia D, Celi FS. Peripheral metabolism of thyroid hormone and glucose homeostasis. Thyroid. 2005;15:899–903.

    Article  CAS  PubMed  Google Scholar 

  48. Benvenga S, Pintaudi B, Vita R, Di Vieste G, Di Benedetto A. Serum thyroid hormone autoantibodies in type 1 diabetes mellitus. J Clin Endocrinol Metab. 2015;100:1870–8.

    Article  CAS  PubMed  Google Scholar 

  49. Nordio M, Pajalich R. Combined treatment with myo-inositol and selenium ensures euthyroidism in subclinical hypothyroidism patients with autoimmune thyroiditis. J Thyr Research. 2013;2013:424163.

    Google Scholar 

  50. Duntas LH, Benvenga S. Selenium: an element for life. Endocrine. 2015;48:756–75.

    Article  CAS  PubMed  Google Scholar 

  51. Koch CA, Diamanti-Kandarakis E. Introduction to endocrine disrupting chemicals - is it time to act? Rev Endocr Metab Disord. 2015;16:269–70.

    Article  PubMed  Google Scholar 

  52. Duntas LH, Mantzou E, Koutras DA. Effects of a six month treatment with selenomethionine in patients with autoimmune thyroiditis. Eur J Endocrinol. 2003;148:389–93.

    Article  CAS  PubMed  Google Scholar 

  53. Mazokopakis EE, Papadakis JA, Papadomanolaki MG, Batistakis AG, Giannakopoulos TG, Protopapadakis EE, Ganotakis ES. Effects of 12 months treatment with L-selenomethionine on serum anti-TPO levels in patients with Hashimoto’s thyroiditis. Thyroid. 2007;17:609–12.

    Article  CAS  PubMed  Google Scholar 

  54. Balázs C. The effect of selenium therapy on autoimmune thyroiditis. Orv Hetil. 2008;149:1227–32.

    Article  PubMed  Google Scholar 

  55. Zhu L, Bai X, Teng WP, Shan ZY, Wang WW, Fan CL, Wang H, Zhang HM. Effects of selenium supplementation on antibodies of autoimmune thyroiditis. Zhonghua Yi Xue Za Zhi. 2012;92:2256–60.

    CAS  PubMed  Google Scholar 

  56. Negro R, Greek G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol Metab. 2007;92:1263–8.

    Article  CAS  PubMed  Google Scholar 

  57. Gumbleton M, Kerr WG. Role of inositol phospholipid signaling in natural killer cell biology. Front Immunol. 2013;4:47.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Fruman DA, Bismuth G. Fine tuning the immune response with PI3K. Immunol Rev. 2009;228:253–72.

    Article  CAS  PubMed  Google Scholar 

  59. Kashiwada M, Lu P, Rothman PB. PIP3 pathway in regulatory T cells and autoimmunity. Immunol Res. 2007;39:194–224.

    Article  CAS  PubMed  Google Scholar 

  60. Séïté JF, Goutsmedt C, Youinou P, Pers JO, Hillion S. Intravenous immunoglobulin induces a functional silencing program similar to anergy in human B cells. J Allergy Clin Immunol. 2014;133:181–8–e1–9.

    Article  Google Scholar 

  61. Tsubata T. Role of inhibitory BCR co-receptors in immunity. Infect Disord Drug Targets. 2012;12:181–90.

    Article  CAS  PubMed  Google Scholar 

  62. Srivastava N, Sudan R, Kerr WG. Role of inositol poly-phosphatases and their targets in T cell biology. Front Immunol. 2013;4:288.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Pouillon V, Maréchal Y, Frippiat C, Erneux C, Schurmans S. Inositol 1,4,5-trisphosphate 3-kinase B (Itpkb) controls survival, proliferation and cytokine production in mouse peripheral T cells. Adv Biol Regul. 2013;53:39–50.

    Article  CAS  PubMed  Google Scholar 

  64. Wang Y, Murakami Y, Yasui T, Wakana S, Kikutani H, Kinoshita T, Maeda Y. Significance of glycosylphosphatidylinositol-anchored protein enrichment in lipid rafts for the control of autoimmunity. J Biol Chem. 2013;288:25490–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Suneel M, Belilos E, Carsons S. Antiphospholipid syndrome. http://emedicine.medscape.com/article/333221-overview. Updated 24 Mar 2015. Accessed 29–02-2016.

  66. Janssen OE, Mehlmauer N, Hahn S, Offner AH, Gartner R. High prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome. Eur J Endocrinol. 2004;150:363–9.

    Article  CAS  PubMed  Google Scholar 

  67. Garelli S, Masiero S, Plebani M, Chen S, Furmaniak J, Armanini D, Betterle C. High prevalence of chronic thyroiditis in patients with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2013;169:248–51.

    Article  CAS  PubMed  Google Scholar 

  68. Du D, Li X. The relationship between thyroiditis and polycystic ovary syndrome: a meta-analysis. Int J Clin Exp Med. 2013;6:880–9.

    PubMed  PubMed Central  Google Scholar 

  69. Ott J, Aust S, Kurz C, Kurz C, Nouri K, Wirth S, Huber JC, Mayerhofer K. Elevated antithyroid peroxidase antibodies indicating Hashimoto’s thyroiditis are associated with the treatment response in infertile women with polycystic ovary syndrome. Fertil Steril. 2010;94:2895–7.

    Article  CAS  PubMed  Google Scholar 

  70. Sinha U, Sinharay K, Saha S, Longkumer TA, Baul SN, Pal SK. Thyroid disorders in polycystic ovarian syndrome subjects: a tertiary hospital based cross-sectional study from eastern India. Indian J Endocrinol Metab. 2013;17:304–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Palioura E, Diamanti-Kandarakis E. Polycystic ovary syndrome (PCOS) and endocrine disrupting chemicals (EDCs). Rev Endocr Metab Disord. 2015;16:365–71.

    Article  CAS  PubMed  Google Scholar 

  72. Mutinati M, Desantis S, Rizzo A, Zizza S, Ventriglia G, Pantaleo M, Sciorsci RL. Localization of thyrotropin receptor and thyroglobulin in the bovine corpus luteum. Anim Reprod Sci. 2010;118:1–6.

    Article  CAS  PubMed  Google Scholar 

  73. Katulande P, Kariyawasam SS, Senanayake HM, Weerakkodi M. Multicystic ovaries and pituitary pseudo-adenoma associated with primary hypothyroidism. J Obstet Gynaecol. 2013;33:17–9.

    Article  CAS  PubMed  Google Scholar 

  74. Li Q, Yang G, Wang Y, Zhang X, Sang Q, Wang H, Zhao X, Xing Q, He L, Wang L. Common genetic variation in the 3′-untranslated region of gonadotropin-releasing hormone receptor regulates gene expression in cella and is associated with thyroid function, insulin secretion as well as insulin sensitivity in polycystic ovary syndrome patients. Hum Genet. 2011;129:553–61.

    Article  CAS  PubMed  Google Scholar 

  75. Zou S, Sang Q, Wang H, Feng R, Li Q, Zhao X, Xing Q, Jin L, He L, Wang L. Common genetic variation in CYP1B1 is associated with concentrations of T4, FT3 and FT4 in the sera of polycystic ovary syndrome patients. Mol Biol Rep. 2013;40:3315–20.

    Article  CAS  PubMed  Google Scholar 

  76. Ghosh S, Kabir SN, Pakrashi A, Chatterjee S, Chakravarty B. Subclinical hypothyroidism: a determinant of polycystic ovary syndrome. Horm Res. 1993;39:61–6.

    Article  CAS  PubMed  Google Scholar 

  77. Muderris II, Boztosun A, Oner G, Bayram F. Effect of thyroid hormone replacement therapy on ovarian volume and androgen hormones in patients with untreated primary hypothyroidism. Ann Saudi Med. 2011;31:145–51.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Ganie MA, Marwaha RK, Aggarwal R, Singh S. High prevalence of polycystic ovary syndrome characteristics in girls with euthyroid chronic lymphocytic thyroiditis: a case-control study. Eur J Endocrinol. 2010;162:1117–22.

    Article  CAS  PubMed  Google Scholar 

  79. Romagnani S. The Th1/Th2 paradigm and allergic disorders. Allergy. 1998;53(Supp 46):12–5.

    Article  CAS  PubMed  Google Scholar 

  80. Orgiazzi J. Thyroid autoimmunity. Presse Med. 2012;41:e611–25.

    Article  PubMed  Google Scholar 

  81. Antonelli A, Fallahi P, Ferrari SM, Pupilli C, d’Annunzio G, Lorini R, Vanelli M, Ferrannini E. Serum Th1 (CXCL10) and Th2 (CCL2) chemokine levels in children with newly diagnosed type 1 diabetes: a longitudinal study. Diabet Med. 2008;25:1349–53.

    CAS  PubMed  Google Scholar 

  82. Antonelli A, Ferri C, Fallahi P, Cazzato M, Ferrari SM, Sebastiani M, Ferrannini E. Clinical and subclinical autoimmune thyroid disorders in systemic sclerosis. Eur J Endocrinol. 2007;156:431–7.

    Article  CAS  PubMed  Google Scholar 

  83. Antonelli A, Ferri C, Fallahi P, Ferrari SM, Frascerra S, Carpi A, Nicolini A, Ferrannini E. Alpha-chemokine CXCL10 and beta-chemokine CCL2 serum levels in patients with hepatitis C-associated cryoglobulinemia in the presence or absence of autoimmune thyroiditis. Metabolism. 2008;57:1270–7.

    Article  CAS  PubMed  Google Scholar 

  84. Antonelli A, Ferrari SM, Giuggioli D, Ferrannini E, Ferri C, Fallahi P. Chemokine (C-X-C motif) ligand (CXCL)10 in autoimmune diseases. Autoimmun Rev. 2014;13:272–80.

    Article  CAS  PubMed  Google Scholar 

  85. Kung AW, Lau KS, Wong NS. Interferon-gamma increases intracellular calcium and inositol phosphates in primary human thyroid cell culture. Endocrinology. 1995;136:5028–33.

    CAS  PubMed  Google Scholar 

  86. Kung AW, Lau KS. Gamma-interferon activates a nuclear protein that binds to the gamma-interferon activation site of the thyroglobulin gene. J Mol Endocrinol. 1998;20:293–8.

    Article  CAS  PubMed  Google Scholar 

  87. Makhsida N, Shah J, Yan G, Fisch H, Shabsigh R. Hypogonadism and metabolic syndrome: implications for testosterone therapy. J Urol. 2005;174:827–34.

    Article  CAS  PubMed  Google Scholar 

  88. Morrison CD, Brannigan RE. Metabolic syndrome and infertility in men. Best Pract Res Clin Obstet Gynaecol. 2015;29:507–15.

    Article  PubMed  Google Scholar 

  89. Traish AM, Zitzmann M. The complex and multifactorial relationship between testosterone deficiency (TD), obesity and vascular disease. Rev Endocr Metab Disord. 2015;16:249–68.

    Article  CAS  PubMed  Google Scholar 

  90. Ullah MI, Washington T, Kazi M, Tamanna S, Koch CA. Testosterone deficiency as a risk factor for cardiovascular disease. Horm Metab Res. 2011;43:153–64.

    Article  CAS  PubMed  Google Scholar 

  91. Costa RR, Varanda WA, Franci CR. A calcium-induced calcium release mechanism supports luteinizing hormone-induced testosterone secretion in mouse Leydig cells. Am J Physiol Cell Physiol. 2010;299:C316–23.

    Article  CAS  PubMed  Google Scholar 

  92. Rothschild G, Sottas CM, Kissel H, Agosti V, Manova K, Hardy MP, Besmer P. A role for kit receptor signaling in Leydig cell steroidogenesis. Biol Reprod. 2003;69:925–32.

    Article  CAS  PubMed  Google Scholar 

  93. Blume-Jensen P, Jiang G, Hyman R, Lee KF, O’Gorman S, Hunter T. Kit/stem cell factor receptor-induced activation of phosphatidylinositol 3′-kinase is essential for male fertility. Nat Genet. 2000;24:157–62.

    Article  CAS  PubMed  Google Scholar 

  94. Casulari LA, Caldas AD. Domingues Casulari Motta L. Lofrano-Porto A Effects of metformin and short-term lifestyle modification on the improvement of male hypogonadism associated with metabolic syndrome Minerva Endocrinol. 2010;35:145–51.

    CAS  PubMed  Google Scholar 

  95. Bevilacqua A, Carlomagno G, Gerli S, Montanino Oliva M, Devroey P, Lanzone A, Soulange C, Facchinetti F, Carlo Di Renzo G, Bizzarri M, Hod M, Cavalli P, D’Anna R, Benvenga S, Chiu TT, Kamenov ZA. Results from the international consensus conference on myo-inositol and D-chiro-inositol in obstetrics and gynecology. Gynecol Endocrinol. 2015;31:441–6.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Messina School of Medicine, via Consolare Valeria, 1, 98125, Messina, Italy

    Salvatore Benvenga

  2. Master Program of Childhood, Adolescence and Women’s Endocrine Health, University of Messina School of Medicine, via Consolare Valeria, 1, 98125, Messina, Italy

    Salvatore Benvenga

  3. Interdepartmental Program of Molecular & Clinical Endocrinology, and Women’s Endocrine Health, University hospital, Padiglione H, 4 piano, Policlinico G. Martino, 98125, Messina, Italy

    Salvatore Benvenga

  4. Department of Clinical and Experimental Medicine, University of Pisa, 56126, Pisa, Italy

    Alessandro Antonelli

Authors
  1. Salvatore Benvenga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alessandro Antonelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Salvatore Benvenga.

Ethics declarations

Funding

The authors have nothing to declare.

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Benvenga, S., Antonelli, A. Inositol(s) in thyroid function, growth and autoimmunity. Rev Endocr Metab Disord 17, 471–484 (2016). https://doi.org/10.1007/s11154-016-9370-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11154-016-9370-3

Keywords

Search

Navigation