A link between hypothyroidism, obesity and male reproduction

References

1. Mullur R, Liu YY, Brent GA. Thyroid hormone regulation of metabolism. Physiol Rev 2014;94:355–82.10.1152/physrev.00030.2013Search in Google Scholar

2. Gronich N, Deftereos SN, Lavi I, Persidis AS, Abernethy DR, Rennert G. Hypothyroidism is a risk factor for new-onset diabetes: a cohort study. Diabetes Care 2015;38:1657–64.10.2337/dc14-2515Search in Google Scholar

3. Gierach M, Gierach J, Junik R. Insulin resistance and thyroid disorders. Endokrynol Pol 2014;65:70–6.10.5603/EP.2014.0010Search in Google Scholar

4. Longhi S, Radetti G. Thyroid function and obesity. J Clin Res Pediatr Endocrinol 2013;5:Suppl 1:40–4.Search in Google Scholar

5. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 1998;395:763–70.10.1038/27376Search in Google Scholar

6. Bluher S, Mantzoros CS. Leptin in reproduction. Curr Opin Endocrinol Diabetes Obes 2007;14:458–64.10.1097/MED.0b013e3282f1cfdcSearch in Google Scholar

7. Fugassa E, Palmero S, Gallo G. Triiodothyronine decreases the production of androgen binding protein by rat Sertoli cells. Biochem Bioph Res Co 1987;143:241–7.10.1016/0006-291X(87)90656-5Search in Google Scholar

8. Palmero S, de Marchis M, Leone M, Fugassa E. [Effect of the administration of triiodothyronine on the metabolism of Sertoli cells in rats]. B Soc Ital Biol Sper 1987;63:415–20.Search in Google Scholar

9. Tena-Sempere M, Barreiro ML. Leptin in male reproduction: the testis paradigm. Mol Cell Endocrinol 2002;188:9–13.10.1016/S0303-7207(02)00008-4Search in Google Scholar

10. Bates JM, St Germain DL, Galton VA. Expression profiles of the three iodothyronine deiodinases, D1, D2, and D3, in the developing rat. Endocrinology 1999;140:844–51.10.1210/endo.140.2.6537Search in Google Scholar PubMed

11. Wajner SM, dos Santos Wagner M, Melo RC, Parreira GG, Chiarini-Garcia H, Bianco AC, Fekete C, Sanchez E, Lechan RM, Maia AL. Type 2 iodothyronine deiodinase is highly expressed in germ cells of adult rat testis. J Endocrinol 2007;194:47–54.10.1677/JOE-07-0106Search in Google Scholar PubMed

12. Galton VA, Schneider MJ, Clark AS, St Germain DL. Life without thyroxine to 3,5,3′-triiodothyronine conversion: studies in mice devoid of the 5′-deiodinases. Endocrinology 2009;150:2957–63.10.1210/en.2008-1572Search in Google Scholar PubMed PubMed Central

13. Schneider MJ, Fiering SN, Pallud SE, Parlow AF, St Germain DL, Galton VA. Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4. Mol Endocrinol 2001;15:2137–48.10.1210/mend.15.12.0740Search in Google Scholar

14. Schneider MJ, Fiering SN, Thai B, Wu SY, St Germain E, Parlow AF, St Germain DL, Galton VA. Targeted disruption of the type 1 selenodeiodinase gene (Dio1) results in marked changes in thyroid hormone economy in mice. Endocrinology 2006;147:580–9.10.1210/en.2005-0739Search in Google Scholar

15. Hernandez A, Martinez ME, Fiering S, Galton VA, St Germain D. Type 3 deiodinase is critical for the maturation and function of the thyroid axis. J Clin Invest 2006;116:476–84.10.1172/JCI26240Search in Google Scholar

16. Arambepola NK, Bunick D, Cooke PS. Thyroid hormone and follicle-stimulating hormone regulate Mullerian-inhibiting substance messenger ribonucleic acid expression in cultured neonatal rat Sertoli cells. Endocrinology 1998;139:4489–95.10.1210/endo.139.11.6315Search in Google Scholar

17. Jannini EA, Crescenzi A, Rucci N, Screponi E, Carosa E, de Matteis A, Macchia E, d’Amati G, D’Armiento M. Ontogenetic pattern of thyroid hormone receptor expression in the human testis. J Clin Endocr Metab 2000;85:3453–7.10.1210/jcem.85.9.6803Search in Google Scholar

18. Jannini EA, Dolci S, Ulisse S, Nikodem VM. Developmental regulation of the thyroid hormone receptor alpha 1 mRNA expression in the rat testis. Mol Endocrinol 1994;8:89–96.10.1210/mend.8.1.8152433Search in Google Scholar

19. O’Shea PJ, Williams GR. Insight into the physiological actions of thyroid hormone receptors from genetically modified mice. J Endocrinol 2002;175:553–70.10.1677/joe.0.1750553Search in Google Scholar

20. Burgos-Trinidad M, Koenig RJ. Dominant negative activity of thyroid hormone receptor variant alpha2 and interaction with nuclear corepressors. Mol Cell Endocrinol 1999;149:107–14.10.1016/S0303-7207(98)00253-6Search in Google Scholar

21. Tagami T, Kopp P, Johnson W, Arseven OK, Jameson JL. The thyroid hormone receptor variant alpha2 is a weak antagonist because it is deficient in interactions with nuclear receptor corepressors. Endocrinology 1998;139:2535–44.10.1210/endo.139.5.6011Search in Google Scholar PubMed

22. Buzzard JJ, Morrison JR, O’Bryan MK, Song Q, Wreford NG. Developmental expression of thyroid hormone receptors in the rat testis. Biol Reprod 2000;62:664–9.10.1095/biolreprod62.3.664Search in Google Scholar PubMed

23. Holsberger DR, Kiesewetter SE, Cooke PS. Regulation of neonatal Sertoli cell development by thyroid hormone receptor alpha1. Biol Reprod 2005;73:396–403.10.1095/biolreprod.105.041426Search in Google Scholar PubMed

24. Fumel B, Guerquin MJ, Livera G, Staub C, Magistrini M, Gauthier C, Flamant F, Guillou F, Fouchécourt S. Thyroid hormone limits postnatal Sertoli cell proliferation in vivo by activation of its alpha1 isoform receptor (TRalpha1) present in these cells and by regulation of Cdk4/JunD/c-myc mRNA levels in mice. Biol Reprod 2012;87:16, 1–9.10.1095/biolreprod.111.098418Search in Google Scholar

25. Hadj-Sahraoui N, Seugnet I, Ghorbel MT, Demeneix B. Hypothyroidism prolongs mitotic activity in the post-natal mouse brain. Neurosci Lett 2000;280:79–82.10.1016/S0304-3940(00)00768-0Search in Google Scholar

26. Sridharan S, Simon L, Meling DD, Cyr DG, Gutstein DE, Fishman GI, Guillou F, Cooke PS. Proliferation of adult sertoli cells following conditional knockout of the Gap junctional protein GJA1 (connexin 43) in mice. Biol Reprod 2007;76:804–12.10.1095/biolreprod.106.059212Search in Google Scholar PubMed

27. Tarulli GA, Stanton PG, Meachem SJ. Is the adult Sertoli cell terminally differentiated? Biol Reprod 2012;87:13, 1–1.10.1095/biolreprod.111.095091Search in Google Scholar PubMed

28. Mendis-Handagama SM, Ariyaratne HB, Teunissen van Manen KR, Haupt RL. Differentiation of adult Leydig cells in the neonatal rat testis is arrested by hypothyroidism. Biol Reprod 1998;59:351–7.10.1095/biolreprod59.2.351Search in Google Scholar PubMed

29. Ariyaratne HB, Mendis-Handagama SM, Mason JI. Effects of tri-iodothyronine on testicular interstitial cells and androgen secretory capacity of the prepubertal Rat. Biol Reprod 2000;63:493–502.10.1093/biolreprod/63.2.493Search in Google Scholar PubMed

30. Teerds KJ, de Rooij DG, de Jong FH, van Haaster LH. Development of the adult-type Leydig cell population in the rat is affected by neonatal thyroid hormone levels. Biol Reprod 1998;59:344–50.10.1095/biolreprod59.2.344Search in Google Scholar PubMed

31. Hardy MP, Sharma RS, Arambepola NK, Sottas CM, Russell LD, Bunick D, Hess RA, Cooke PS. Increased proliferation of Leydig cells induced by neonatal hypothyroidism in the rat. J Androl 1996;17:231–8.10.1002/j.1939-4640.1996.tb01778.xSearch in Google Scholar

32. Racine C, Rey R, Forest MG, Louis F, Ferre A, Huhtaniemi I, Josso N, di Clemente N. Receptors for anti-mullerian hormone on Leydig cells are responsible for its effects on steroidogenesis and cell differentiation. Proc Natl Acad Sci USA 1998;95:594–9.10.1073/pnas.95.2.594Search in Google Scholar PubMed PubMed Central

33. Maran RR. Thyroid hormones: their role in testicular steroidogenesis. Arch Andrology 2003;49:375–88.10.1080/01485010390204968Search in Google Scholar PubMed

34. Mendis-Handagama SM, Siril Ariyaratne HB. Leydig cells, thyroid hormones and steroidogenesis. Indian J Exp Biol 2005;43:939–62.Search in Google Scholar

35. Chang YJ, Hwu CM, Yeh CC, Wang PS, Wang SW. Effects of subacute hypothyroidism on metabolism and growth-related molecules. Molecules 2014;19:11178–95.10.3390/molecules190811178Search in Google Scholar PubMed PubMed Central

36. Werner SCI, Braverman LE, Utiger RD. Werner & Ingbar’s the thyroid: a fundamental and clinical text, 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2005. 1166 p.Search in Google Scholar

37. Holsberger DR, Buchold GM, Leal MC, Kiesewetter SE, O’Brien DA, Hess RA, França LR, Kiyokawa H, Cooke PS. Cell-cycle inhibitors p27Kip1 and p21Cip1 regulate murine Sertoli cell proliferation. Biol Reprod 2005;72:1429–36.10.1095/biolreprod.105.040386Search in Google Scholar

38. Ulisse S, Jannini EA, Carosa E, Piersanti D, Graziano FM, D’Armiento M. Inhibition of aromatase activity in rat Sertoli cells by thyroid hormone. J Endocrinol 1994;140:431–6.10.1677/joe.0.1400431Search in Google Scholar

39. Ando S, Sirianni R, Forastieri P, Casaburi I, Lanzino M, Rago V, Giordano F, Giordano C, Carpino A, Pezzi V. Aromatase expression in prepuberal Sertoli cells: effect of thyroid hormone. Mol Cell Endocrinol 2001;178:11–21.10.1016/S0303-7207(01)00443-9Search in Google Scholar

40. Catalano S, Pezzi V, Chimento A, Giordano C, Carpino A, Young M, McPhaul MJ, Andò S. Triiodothyronine decreases the activity of the proximal promoter (PII) of the aromatase gene in the mouse Sertoli cell line, TM4. Mol Endocrinol 2003;17:923–34.10.1210/me.2002-0102Search in Google Scholar PubMed

41. Arambepola NK, Bunick D, Cooke PS. Thyroid hormone effects on androgen receptor messenger RNA expression in rat Sertoli and peritubular cells. J Endocrinol 1998;156:43–50.10.1677/joe.0.1560043Search in Google Scholar PubMed

42. Romano RM, Bargi-Souza P, Brunetto EL, Goulart-Silva F, Avellar MC, Oliveira CA, Nunes MT. Hypothyroidism in adult male rats alters posttranscriptional mechanisms of luteinizing hormone biosynthesis. Thyroid 2013;23:497–505.10.1089/thy.2011.0514Search in Google Scholar PubMed

43. Gilleron J, Nebout M, Scarabelli L, Senegas-Balas F, Palmero S, Segretain D, Pointis G. A potential novel mechanism involving connexin 43 gap junction for control of sertoli cell proliferation by thyroid hormones. J Cell Physiol 2006;209:153–61.10.1002/jcp.20716Search in Google Scholar PubMed

44. Maran RR, Arunakaran J, Aruldhas MM. T3 directly stimulates basal and modulates LH induced testosterone and oestradiol production by rat Leydig cells in vitro. Endocr J 2000;47: 417–28.10.1507/endocrj.47.417Search in Google Scholar PubMed

45. Gao Y, Lee WM, Cheng CY. Thyroid hormone function in the rat testis. Front Endocrinol (Lausanne) 2014;5:188.10.3389/fendo.2014.00188Search in Google Scholar PubMed PubMed Central

46. Herrid M, O’Shea T, McFarlane JR. Ontogeny of leptin and its receptor expression in mouse testis during the postnatal period. Mol Reprod Dev 2008;75:874–80.10.1002/mrd.20796Search in Google Scholar PubMed

47. Cioffi JA, Shafer AW, Zupancic TJ, Smith-Gbur J, Mikhail A, Platika D, Snodgrass HR. Novel B219/OB receptor isoforms: possible role of leptin in hematopoiesis and reproduction. Nat Med 1996;2:585–9.10.1038/nm0596-585Search in Google Scholar PubMed

48. Malendowicz W, Rucinski M, Macchi C, Spinazzi R, Ziolkowska A, Nussdorfer GG, Kwias Z. Leptin and leptin receptors in the prostate and seminal vesicles of the adult rat. Int J Mol Med 2006;18:615–8.10.3892/ijmm.18.4.615Search in Google Scholar

49. Morash B, Li A, Murphy PR, Wilkinson M, Ur E. Leptin gene expression in the brain and pituitary gland. Endocrinology 1999;140:5995–8.10.1210/endo.140.12.7288Search in Google Scholar PubMed

50. Jin L, Zhang S, Burguera BG, Couce ME, Osamura RY, Kulig E, Lloyd RV. Leptin and leptin receptor expression in rat and mouse pituitary cells. Endocrinology 2000;141:333–9.10.1210/endo.141.1.7260Search in Google Scholar PubMed

51. Caprio M, Isidori AM, Carta AR, Moretti C, Dufau ML, Fabbri A. Expression of functional leptin receptors in rodent Leydig cells. Endocrinology 1999;140:4939–47.10.1210/endo.140.11.7088Search in Google Scholar PubMed

52. Ahima RS. Adipose tissue as an endocrine organ. Obesity 2006;14 Suppl 5:242S-9S.10.1038/oby.2006.317Search in Google Scholar PubMed

53. Considine RV. Regulation of leptin production. Rev Endocr Metab Disord 2001;2:357–63.10.1023/A:1011896331159Search in Google Scholar

54. Wauters M, Considine RV, Van Gaal LF. Human leptin: from an adipocyte hormone to an endocrine mediator. Eur J Endocrinol 2000;143:293–311.10.1530/eje.0.1430293Search in Google Scholar PubMed

55. Colli S, Silveira Cavalcante F, Peixoto Martins M, Sampaio FJ, da Fonte Ramos C. Leptin role in the rat prostate ventral lobe. Fertil Steril 2011;95:1490–3 e1.10.1016/j.fertnstert.2010.12.029Search in Google Scholar PubMed

56. Korner J, Savontaus E, Chua SC, Jr., Leibel RL, Wardlaw SL. Leptin regulation of Agrp and Npy mRNA in the rat hypothalamus. J Neuroendocrinol 2001;13:959–66.10.1046/j.1365-2826.2001.00716.xSearch in Google Scholar PubMed

57. Swart I, Jahng JW, Overton JM, Houpt TA. Hypothalamic NPY, AGRP, and POMC mRNA responses to leptin and refeeding in mice. Am J Physiol Regul Integr Comp Physiol 2002;283:R1020–6.10.1152/ajpregu.00501.2001Search in Google Scholar PubMed

58. Banks WA, McLay RN, Kastin AJ, Sarmiento U, Scully S. Passage of leptin across the blood-testis barrier. Am J Physiol 1999;276:E1099–104.10.1152/ajpendo.1999.276.6.E1099Search in Google Scholar PubMed

59. Tena-Sempere M, Pinilla L, Gonzalez LC, Dieguez C, Casanueva FF, Aguilar E. Leptin inhibits testosterone secretion from adult rat testis in vitro. J Endocrinol 1999;161:211–8.10.1677/joe.0.1610211Search in Google Scholar PubMed

60. Tena-Sempere M, Manna PR, Zhang FP, Pinilla L, Gonzalez LC, Dieguez C, Huhtaniemi I, Aguilar E. Molecular mechanisms of leptin action in adult rat testis: potential targets for leptin-induced inhibition of steroidogenesis and pattern of leptin receptor messenger ribonucleic acid expression. J Endocrinol 2001;170:413–23.10.1677/joe.0.1700413Search in Google Scholar PubMed

61. Alves-Pereira JL, Colli S, Marques DS, Sampaio FJ, Ramos CF. Molecular and morphometric analysis of the rat ventral prostate injected with leptin. Regul Peptides 2012;176:6–12.10.1016/j.regpep.2012.02.002Search in Google Scholar PubMed

62. Lebrethon MC, Vandersmissen E, Gerard A, Parent AS, Junien JL, Bourguignon JP. In vitro stimulation of the prepubertal rat gonadotropin-releasing hormone pulse generator by leptin and neuropeptide Y through distinct mechanisms. Endocrinology 2000;141:1464–9.10.1210/endo.141.4.7432Search in Google Scholar PubMed

63. Quennell JH, Mulligan AC, Tups A, Liu X, Phipps SJ, Kemp CJ, Herbison AE, Grattan DR, Anderson GM. Leptin indirectly regulates gonadotropin-releasing hormone neuronal function. Endocrinology 2009;150:2805–12.10.1210/en.2008-1693Search in Google Scholar PubMed PubMed Central

64. Wabitsch M, Blum WF, Muche R, Braun M, Hube F, Rascher W, Heinze E, Teller W, Hauner H. Contribution of androgens to the gender difference in leptin production in obese children and adolescents. J Clin Invest 1997;100:808–13.10.1172/JCI119595Search in Google Scholar PubMed PubMed Central

65. Luukkaa V, Pesonen U, Huhtaniemi I, Lehtonen A, Tilvis R, Tuomilehto J, Koulu M, Huupponen R. Inverse correlation between serum testosterone and leptin in men. J Clin Endocrinol Metab 1998;83:3243–6.10.1210/jc.83.9.3243Search in Google Scholar

66. Habib CN, Al-Abd AM, Tolba MF, Khalifa AE, Khedr A, Mosli HA, Abdel-Naim AB. Leptin influences estrogen metabolism and accelerates prostate cell proliferation. Life Sci 2015;121:10–5.10.1016/j.lfs.2014.11.007Search in Google Scholar PubMed

67. Liu E, Samad F, Mueller BM. Local adipocytes enable estrogen-dependent breast cancer growth: role of leptin and aromatase. Adipocyte 2013;2:165–9.10.4161/adip.23645Search in Google Scholar PubMed PubMed Central

68. Subbaramaiah K, Howe LR, Bhardwaj P, Du B, Gravaghi C, Yantiss RK, Zhou XK, Blaho VA, Hla T, Yang P, Kopelovich L, Hudis CA, Dannenberg AJ. Obesity is associated with inflammation and elevated aromatase expression in the mouse mammary gland. Cancer Prev Res (Phila) 2011;4:329–46.10.1158/1940-6207.CAPR-10-0381Search in Google Scholar PubMed PubMed Central

69. Gill MS, Hall CM, Tillmann V, Clayton PE. Constitutional delay in growth and puberty (CDGP) is associated with hypoleptinaemia. Clin Endocrinol 1999;50:721–6.10.1046/j.1365-2265.1999.00736.xSearch in Google Scholar PubMed

70. Palmert MR, Radovick S, Boepple PA. The impact of reversible gonadal sex steroid suppression on serum leptin concentrations in children with central precocious puberty. J Clin Endocr Metab 1998;83:1091–6.10.1210/jc.83.4.1091Search in Google Scholar

71. Yuan M, Huang G, Li J, Zhang J, Li F, Li K, Gao B, Zeng L, Shan W, Lin P, Huang L. Hyperleptinemia directly affects testicular maturation at different sexual stages in mice, and suppressor of cytokine signaling 3 is involved in this process. Reprod Biol Endocrinol 2014;12:15.10.1186/1477-7827-12-15Search in Google Scholar PubMed PubMed Central

72. Jope T, Lammert A, Kratzsch J, Paasch U, Glander HJ. Leptin and leptin receptor in human seminal plasma and in human spermatozoa. Int J Androl 2003;26:335–41.10.1111/j.1365-2605.2003.00434.xSearch in Google Scholar PubMed

73. Van Vliet G, Deladoey J. Diagnosis, treatment and outcome of congenital hypothyroidism. Endocr Dev 2014;26:50–9.10.1159/000363155Search in Google Scholar PubMed

74. Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, Grimley Evans J, Hasan DM, Rodgers H, Tunbridge F, Young ET. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf) 1995;43:55–68.10.1111/j.1365-2265.1995.tb01894.xSearch in Google Scholar PubMed

75. El-Sakka AI, Hassoba HM, Sayed HM, Tayeb KA. Pattern of endocrinal changes in patients with sexual dysfunction. J Sex Med 2005;2:551–8.10.1111/j.1743-6109.2005.00082.xSearch in Google Scholar PubMed

76. Wassner AJ, Brown RS. Hypothyroidism in the newborn period. Curr Opin Endocrinol Diabetes Obes 2013;20:449–54.10.1097/01.med.0000433063.78799.c2Search in Google Scholar PubMed PubMed Central

77. Ramos HE, Nesi-Franca S, Maciel RM. [New aspects of genetics and molecular mechanisms on thyroid morphogenesis for the understanding of thyroid dysgenesia]. Arq Bras Endocrinol Metabol 2008;52:1403–15.10.1590/S0004-27302008000900003Search in Google Scholar

78. Wassner AJ, Brown RS. Congenital hypothyroidism: recent advances. Curr Opin Endocrinol Diabetes Obes 2015;22:407–12.10.1097/MED.0000000000000181Search in Google Scholar

79. Carreau S, Silandre D, Bois C, Bouraima H, Galeraud-Denis I, Delalande C. Estrogens: a new player in spermatogenesis. Folia Histochem Cytobiol 2007;45 Suppl 1:S5–10.Search in Google Scholar

80. Papadopoulos V, Carreau S, Szerman-Joly E, Drosdowsky MA, Dehennin L, Scholler R. Rat testis 17 beta-estradiol: identification by gas chromatography-mass spectrometry and age related cellular distribution. J Steroid Biochem 1986;24:1211–6.10.1016/0022-4731(86)90385-7Search in Google Scholar

81. Jannini EA, Ulisse S, D’Armiento M. Thyroid hormone and male gonadal function. Endocr Rev 1995;16:443–59.10.1210/edrv-16-4-443Search in Google Scholar

82. Sisci D, Panno ML, Salerno M, Maggiolini M, Pezzi V, Morrone EG, Mauro L, Aquila S, Marsico S, Lanzino M, Andò S. A time course study on the “in vitro” effects of T3 and testosterone on androgen and estrogen receptors in peripuberal primary rat Sertoli cells. Exp Clin Endocrinol Diabetes 1997;105:218–24.10.1055/s-0029-1211755Search in Google Scholar

83. Pezzi V, Panno ML, Sirianni R, Forastieri P, Casaburi I, Lanzino M, Rago V, Giordano F, Giordano C, Carpino A, Andò S. Effects of tri-iodothyronine on alternative splicing events in the coding region of cytochrome P450 aromatase in immature rat Sertoli cells. J Endocrinol 2001;170:381–93.10.1677/joe.0.1700381Search in Google Scholar

84. Umezu M, Kagabu S, Jiang JY, Niimura S, Sato E. Developmental hormonal profiles in rdw rats with congenital hypothyroidism accompanying increased testicular size and infertility in adulthood. J Rep Dev 2004;50:675–84.10.1262/jrd.50.675Search in Google Scholar

85. Chiao YC, Lee HY, Wang SW, Hwang JJ, Chien CH, Huang SW, Lu CC, Chen JJ, Tsai SC, Wang PS. Regulation of thyroid hormones on the production of testosterone in rats. J Cell Biochem 1999;73:554–62.10.1002/(SICI)1097-4644(19990615)73:4<554::AID-JCB13>3.0.CO;2-LSearch in Google Scholar

86. Krassas GE, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocr Rev 2010;31:702–55.10.1210/er.2009-0041Search in Google Scholar

87. Ortega FJ, Jilkova ZM, Moreno-Navarrete JM, Pavelka S, Rodriguez-Hermosa JI, Kopeck Ygrave J, Fernández-Real JM. Type I iodothyronine 5′-deiodinase mRNA and activity is increased in adipose tissue of obese subjects. Int J Obes (Lond) 2012;36:320–4.10.1038/ijo.2011.101Search in Google Scholar

88. Leonhardt U, Ritzel U, Schafer G, Becker W, Ramadori G. Serum leptin levels in hypo- and hyperthyroidism. J Endocrinol 1998;157:75–9.10.1677/joe.0.1570075Search in Google Scholar

89. Yoshida T, Momotani N, Hayashi M, Monkawa T, Ito K, Saruta T. Serum leptin concentrations in patients with thyroid disorders. Clin Endocrinol 1998;48:299–302.10.1046/j.1365-2265.1998.00408.xSearch in Google Scholar PubMed

90. Sreenan S, Caro JF, Refetoff S. Thyroid dysfunction is not associated with alterations in serum leptin levels. Thyroid 1997;7:407–9.10.1089/thy.1997.7.407Search in Google Scholar PubMed

91. Calvino C, Souza LL, Costa-e-Sousa RH, Almeida NA, Trevenzoli IH, Pazos-Moura CC. Hypothyroidism reduces ObRb-STAT3 leptin signalling in the hypothalamus and pituitary of rats associated with resistance to leptin acute anorectic action. J Endocrinol 2012;215:129–35.10.1530/JOE-11-0476Search in Google Scholar PubMed

92. Groba C, Mayerl S, van Mullem AA, Visser TJ, Darras VM, Habenicht AJ, Heuer H. Hypothyroidism compromises hypothalamic leptin signaling in mice. Mol Endocrinol 2013;27:586–97.10.1210/me.2012-1311Search in Google Scholar PubMed PubMed Central

93. Menendez C, Baldelli R, Camina JP, Escudero B, Peino R, Dieguez C, Casanueva FF. TSH stimulates leptin secretion by a direct effect on adipocytes. J Endocrinol 2003;176:7–12.10.1677/joe.0.1760007Search in Google Scholar PubMed

94. Ortiga-Carvalho TM, Oliveira KJ, Soares BA, Pazos-Moura CC. The role of leptin in the regulation of TSH secretion in the fed state: in vivo and in vitro studies. J Endocrinol 2002;174:121–5.10.1677/joe.0.1740121Search in Google Scholar PubMed

95. Pacifico L, Anania C, Ferraro F, Andreoli GM, Chiesa C. Thyroid function in childhood obesity and metabolic comorbidity. Clin Chim Acta 2012;413:396–405.10.1016/j.cca.2011.11.013Search in Google Scholar PubMed

96. Saúde Md. Vigilância de Fatores de Risco e Proteção para Doenças Crônicas por Inquérito Telefônico. In: Saúde Md, editor. Internet2014.Search in Google Scholar

97. Dandona P, Dhindsa S. Update: hypogonadotropic hypogonadism in type 2 diabetes and obesity. J Clin Endocrinol Metab 2011;96:2643–51.10.1210/jc.2010-2724Search in Google Scholar PubMed PubMed Central

98. Hofstra J, Loves S, van Wageningen B, Ruinemans-Koerts J, Jansen I, de Boer H. High prevalence of hypogonadotropic hypogonadism in men referred for obesity treatment. Neth J Med 2008;66:103–9.Search in Google Scholar

99. Isidori AM, Caprio M, Strollo F, Moretti C, Frajese G, Isidori A, Fabbri A. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. J Clin Endocr Metab 1999;84:3673–80.10.1210/jcem.84.10.6082Search in Google Scholar

100. Esposito K, Giugliano D. Obesity, the metabolic syndrome, and sexual dysfunction in men. Clin Pharmacol Ther 2011;90: 169–73.10.1038/clpt.2011.91Search in Google Scholar PubMed

101. Jones N, Harrison GA. Genetically determined obesity and sterility in the mouse. Proc Soc Study Fertil 1957;9:51–64.Search in Google Scholar

102. Swerdloff RS, Batt RA, Bray GA. Reproductive hormonal function in the genetically obese (ob/ob) mouse. Endocrinology 1976;98:1359–64.10.1210/endo-98-6-1359Search in Google Scholar PubMed

103. Barash IA, Cheung CC, Weigle DS, Ren H, Kabigting EB, Kuijper JL, Clifton DK, Steiner RA. Leptin is a metabolic signal to the reproductive system. Endocrinology 1996;137:3144–7.10.1210/endo.137.7.8770941Search in Google Scholar

104. Ishikawa T, Fujioka H, Ishimura T, Takenaka A, Fujisawa M. Expression of leptin and leptin receptor in the testis of fertile and infertile patients. Andrologia 2007;39:22–7.10.1111/j.1439-0272.2006.00754.xSearch in Google Scholar

105. Zhao J, Zhai L, Liu Z, Wu S, Xu L. Leptin level and oxidative stress contribute to obesity-induced low testosterone in murine testicular tissue. Oxid Med Cell Longev 2014;2014:190945.10.1155/2014/190945Search in Google Scholar

106. Stokes VJ, Anderson RA, George JT. How does obesity affect fertility in men-and what are the treatment options? Clin Endocrinol (Oxf) 2015;82:633–8.10.1111/cen.12591Search in Google Scholar

107. Rago V, Aquila S, Guido C, Carpino A. Leptin and its receptor are expressed in the testis and in the epididymis of young and adult pigs. Anat Rec 2009;292:736–45.10.1002/ar.20880Search in Google Scholar

108. Gombar FM, Ramos CF. Perinatal malnutrition programs gene expression of leptin receptors isoforms in testis and prostate of adult rats. Regul Peptides 2013;184:115–20.10.1016/j.regpep.2013.03.009Search in Google Scholar

109. Inhorn MC. Global infertility and the globalization of new reproductive technologies: illustrations from Egypt. Soc Sci Med 2003;56:1837–51.10.1016/S0277-9536(02)00208-3Search in Google Scholar

110. OMS. Organização Mundial da Saúde. Infertilidade. A tabulação dos dados disponíveis sobre a prevalência da infertilidade primária e secundária http://apps.who.int/iris/bitstream/10665/59769/1/WHO_MCH_91.9.pdf003Fua003D1: Divisão de saúde da família; 2015 [cited 2015 2 de Junho de 2015].Search in Google Scholar