Advertisement

Hormones

, Volume 14, Issue 4, pp 549–562 | Cite as

The impact of adipose tissue-derived factors on the hypothalamic-pituitary-gonadal (HPG) axis

  • Christos Tsatsanis
  • Eirini Dermitzaki
  • Pavlina Avgoustinaki
  • Niki Malliaraki
  • Vasilis Mytaras
  • Andrew N. Margioris
Review

Abstract

Adipose tissue produces factors, including adipokines, cytokines and chemokines which, when released, systemically exert endocrine effects on multiple tissues thereby affecting their physiology. Adipokines also affect the hypothalamic-pituitary-gonadal (HPG) axis both centrally, at the hypothalamic-pituitary level, and peripherally acting on the gonads themselves. Among the adipokines, leptin, adiponectin, resistin, chemerin and the peptide kisspeptin have pleiotropic actions on the HPG axis affecting male and female fertility. Furthermore, adipokines and adipose tissue-produced factors readily affect the immune system resulting in inflammation, which in turn impact the HPG axis, thus evidencing a link between metabolic inflammation and fertility. In this review we provide an overview of the existing extensive bibliography on the crosstalk between adipose tissue-derived factors and the HPG axis, with particular focus on the impact of obesity and the metabolic syndrome on gonadal function and fertility.

Key words

Adipokines Adipose tissue Chemokines Cytokines Fertility Gonads Inflammation Reproduction 

References

  1. 1.
    Dandona P, Aljada A, Bandyopadhyay A, 2004 Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol 25: 4–7.Google Scholar
  2. 2.
    Bruun JM, Lihn AS, Pedersen SB, Richelsen B, 2005 Monocyte chemoattractant protein-1 release is higher in visceral than subcutaneous human adipose tissue (AT): implication of macrophages resident in the AT. J Clin Endocrinol Metab 90: 2282–2289.PubMedGoogle Scholar
  3. 3.
    Suganami T, Nishida J, Ogawa Y, 2005 A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha. Arterioscler Thromb Vasc Biol 25: 2062–2068.PubMedGoogle Scholar
  4. 4.
    Marra F, Valente AJ, Pinzani M, Abboud HE, 1993 Cultured human liver fat-storing cells produce monocyte chemotactic protein-1. Regulation by proinflammatory cytokines. J Clin Invest 92: 1674–1680.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Ballinger AB, Savage MO, Sanderson IR, 2003 Delayed puberty associated with inflammatory bowel disease. Pediatr Res 53: 205–210.PubMedGoogle Scholar
  6. 6.
    DeBoer MD, Li Y, Cohn S, 2013, Colitis causes delay in puberty in female mice out of proportion to changes in leptin and corticosterone. J Gastroenterol 45: 277–284.Google Scholar
  7. 7.
    Chehab FF, Lim ME, Lu R, 1996 Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet 12: 318–320.Google Scholar
  8. 8.
    Farooqi IS, 2002, Leptin and the onset of puberty: insights from rodent and human genetics. Semin Reprod Med 20: 139–144.PubMedGoogle Scholar
  9. 9.
    Nappi RE, Rivest S, 1997 Effect of immune and metabolic challenges on the luteinizing hormone-releasing hormone neuronal system in cycling female rats: an evaluation at the transcriptional level. Endocrinology 138: 1374–1384.PubMedGoogle Scholar
  10. 10.
    Tengstrand B, Carlstrom K, Hafstrom I, 2009 Gonadal hormones in men with rheumatoid arthritis—from onset through 2 years. J Rheumatol 36: 887–892.PubMedGoogle Scholar
  11. 11.
    Klenov VE, Jungheim ES, 2014 Obesity and reproductive function: a review of the evidence. Curr Opin Obstet Gynecol 26: 455–460.PubMedGoogle Scholar
  12. 12.
    Michalakis K, Mintziori G, Kaprara A, Tarlatzis BC, Goulis DG, 2014 The complex interaction between obesity, metabolic syndrome and reproductive axis: a narrative review. Metabolism 62: 457–478.Google Scholar
  13. 13.
    Landry D, Cloutier F, Martin LJ, 2014 Implications of leptin in neuroendocrine regulation of male reproduction. Reprod Biol 13: 1–14.Google Scholar
  14. 14.
    Derby CA, Zilber S, Brambilla D, Morales KH, McKinlay JB, 2006 Body mass index, waist circumference and waist to hip ratio and change in sex steroid hormones: the Massachusetts Male Ageing Study. Clin Endocrinol (Oxf) 65: 125–131.Google Scholar
  15. 15.
    Pehlivanov B, Mitkov M, 2009 Serum leptin levels correlate with clinical and biochemical indices of insulin resistance in women with polycystic ovary syndrome. Eur J Contracept Reprod Health Care 14: 153–159.PubMedGoogle Scholar
  16. 16.
    Goncharov NP, Katsya GV, Chagina NA, Gooren LJ, 2009 Testosterone and obesity in men under the age of 40 years. Andrologia 41: 76–83.PubMedGoogle Scholar
  17. 17.
    Bobjer J, Katrinaki M, Tsatsanis C, Lundberg Giwercman Y, Giwercman A, 2013 Negative association between testosterone concentration and inflammatory markers in young men: a nested cross-sectional study. PLoS One 8: e61466.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Nakao K, Kishi H, Imai F, Suwa H, Hirakawa T, Minegishi T, 2013 TNF-alpha Suppressed FSH-Induced LH Receptor Expression Through Transcriptional Regulation in Rat Granulosa Cells. Endocrinology 156: 3192–3202.Google Scholar
  19. 19.
    Matsuwaki T, Suzuki M, Yamanouchi K, Nishihara M, 2004 Glucocorticoid counteracts the suppressive effect of tumor necrosis factor-alpha on the surge of luteinizing hormone secretion in rats. J Endocrinol 181: 509–513.PubMedGoogle Scholar
  20. 20.
    Kiezun M, Smolinska N, Maleszka A, Dobrzyn K, Szeszko K, Kaminski T, 2014 Adiponectin expression in the porcine pituitary during the estrous cycle and its effect on LH and FSH secretion. Am J Physiol Endocrinol Metab 307: E1038–1046.PubMedGoogle Scholar
  21. 21.
    Dagklis T, Kouvelas D, Kallaras K, et al, 2014, Leptin increases luteinizing hormone secretion of fasting female rats. Clin Exp Obstet Gynecol 42: 18–21.Google Scholar
  22. 22.
    Hedger MP, Meinhardt A, 2003 Cytokines and the immune-testicular axis. J Reprod Immunol 58: 1–26.PubMedGoogle Scholar
  23. 23.
    Maggio M, Basaria S, Ceda GP, et al, 2005 The relationship between testosterone and molecular markers of inflammation in older men. J Endocrinol Invest 28: 11 Suppl Proceedings: 116–119.PubMedGoogle Scholar
  24. 24.
    Mahmood K, Naeem M, Rahimnajjad NA, 2013 Metformin: the hidden chronicles of a magic drug. Eur J Intern Med 24: 20–26.PubMedGoogle Scholar
  25. 25.
    Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM, 1994, Positional cloning of the mouse obese gene and its human homologue. Nature 372: 425–432.Google Scholar
  26. 26.
    Psilopanagioti A, Papadaki H, Kranioti EF, Alexandrides TK, Varakis JN, 2009 Expression of adiponectin and adiponectin receptors in human pituitary gland and brain. Neuroendocrinology 89: 38–47.PubMedGoogle Scholar
  27. 27.
    Burcelin R, Thorens B, Glauser M, Gaillard RC, Pralong FP, 2003 Gonadotropin-releasing hormone secretion from hypothalamic neurons: stimulation by insulin and potentiation by leptin. Endocrinology 144: 4484–4491.PubMedGoogle Scholar
  28. 28.
    Quennell JH, Mulligan AC, Tups A, et al, 2009 Leptin indirectly regulates gonadotropin-releasing hormone neuronal function. Endocrinology 150: 2805–2812.PubMedPubMedCentralGoogle Scholar
  29. 29.
    El-Eshmawy MM, Abdel Aal IA, El Hawary AK, 2013 Association of ghrelin and leptin with reproductive hormones in constitutional delay of growth and puberty. Reprod Biol Endocrinol 8: 153.Google Scholar
  30. 30.
    Jahan S, Bibi R, Ahmed S, Kafeel S, 2014, Leptin levels in infertile males. J Coll Physicians Surg Pak 21: 393–397.Google Scholar
  31. 31.
    von Schnurbein J, Moss A, Nagel SA, et al, 2014 Leptin substitution results in the induction of menstrual cycles in an adolescent with leptin deficiency and hypogonadotropic hypogonadism. Horm Res Paediatr 77: 127–133.Google Scholar
  32. 32.
    Lagowska K, Kapczuk K, Jeszka J, 2014 Nine-month nutritional intervention improves restoration of menses in young female athletes and ballet dancers. J Int Soc Sports Nutr 11: 52.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Mallinson RJ, Williams NI, Olmsted MP, Scheid JL, Riddle ES, De Souza MJ, 2014 A case report of recovery of menstrual function following a nutritional intervention in two exercising women with amenorrhea of varying duration. J Int Soc Sports Nutr 10: 34.Google Scholar
  34. 34.
    Khorram O, Keen-Rinehart E, Chuang TD, Ross MG, Desai M, 2013 Maternal undernutrition induces premature reproductive senescence in adult female rat offspring. Fertil Steril 103: 291–298. e2.Google Scholar
  35. 35.
    Einollahi N, Dashti N, Nabatchian F, 2014 Serum leptin concentrations during the menstrual cycle in Iranian healthy women. Acta Med Iran 48: 300–303.Google Scholar
  36. 36.
    Ma Y, Chen B, Wang H, Hu K, Huang Y, 2013 Prediction of sperm retrieval in men with non-obstructive azoospermia using artificial neural networks: leptin is a good assistant diagnostic marker. Hum Reprod 26: 294–298.Google Scholar
  37. 37.
    Hussain MA, Song WJ, Wolfe A, 2013 There is Kisspeptin — And Then There is Kisspeptin. Trends Endocrinol Metab 26: 564–572.Google Scholar
  38. 38.
    Smith JT, Li Q, Yap KS, et al, 2015 Kisspeptin is essential for the full preovulatory LH surge and stimulates GnRH release from the isolated ovine median eminence. Endocrinology 152: 1001–1012.Google Scholar
  39. 39.
    Backholer K, Smith J, Clarke IJ, 2009 Melanocortins may stimulate reproduction by activating orexin neurons in the dorsomedial hypothalamus and kisspeptin neurons in the preoptic area of the ewe. Endocrinology 150: 5488–5497.PubMedGoogle Scholar
  40. 40.
    Backholer K, Smith JT, Rao A, et al, 2015 Kisspeptin cells in the ewe brain respond to leptin and communicate with neuropeptide Y and proopiomelanocortin cells. Endocrinology 151: 2233–2243.Google Scholar
  41. 41.
    Castellano JM, Bentsen AH, Mikkelsen JD, Tena-Sempere M, 2015 Kisspeptins: bridging energy homeostasis and reproduction. Brain Res 1364: 129–138.Google Scholar
  42. 42.
    Castellano JM, Roa J, Luque RM, et al, 2009 KiSS-1/kisspeptins and the metabolic control of reproduction: physiologic roles and putative physiopathological implications. Peptides 30: 139–145.PubMedGoogle Scholar
  43. 43.
    Castellano JM, Fena-Sempere M, 2014 Metabolic regulation of kisspeptin. Adv Exp Med Biol 784: 363–383.Google Scholar
  44. 44.
    De Bond JA, Smith JF, 2015 Kisspeptin and energy balance in reproduction. Reproduction 147: R53–63.Google Scholar
  45. 45.
    Lapatto R, Pallais JC, Zhang D, et al, 2007 Kiss1-/-mice exhibit more variable hypogonadism than Gpr54-/- mice. Endocrinology 148: 4927–4936.PubMedGoogle Scholar
  46. 46.
    Castellano JM, Navarro VM, Fernandez-Fernandez R, et al, 2005 Changes in hypothalamic KiSS-1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in undernutrition. Endocrinology 146: 3917–3925.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Clarke IJ, 2015 Interface between metabolic balance and reproduction in ruminants: focus on the hypothalamus and pituitary. Horm Behav 66: 15–40.Google Scholar
  48. 48.
    Fu LY, van den Pol AN, 2014 Kisspeptin directly excites anorexigenic proopiomelanocortin neurons but inhibits orexigenic neuropeptide Y cells by an indirect synaptic mechanism. J Neurosci 30: 10205–10219.Google Scholar
  49. 49.
    Brown RE, Imran SA, Ur E, Wilkinson M, 2008 KiSS-1 mRNA in adipose tissue is regulated by sex hormones and food intake. Mol Cell Endocrinol 281: 64–72.PubMedGoogle Scholar
  50. 50.
    Semple RK, Achermann JC, Ellery J, et al, 2005 Fwo novel missense mutations in g protein-coupled receptor 54 in a patient with hypogonadotropic hypogonadism. J Clin Endocrinol Metab 90: 1849–1855.PubMedGoogle Scholar
  51. 51.
    Pinilla L, Aguilar E, Dieguez C, Millar RP, Fena-Sempere M, 2015 Kisspeptins and reproduction: physiological roles and regulatory mechanisms. Physiol Rev 92: 1235–1316.Google Scholar
  52. 52.
    Plant FM, 2013 Neuroendocrine control of the onset of puberty. Front Neuroendocrinol 38: 73–88.Google Scholar
  53. 53.
    Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF, 1995 A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 270: 26746–26749.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Groeneveld MP, Huang-Doran I, Semple RK, 2013 Adiponectin and leptin in human severe insulin resistance — diagnostic utility and biological insights. Biochimie 94: 2172–2179.Google Scholar
  55. 55.
    Ohashi K, Ouchi N, Matsuzawa Y, 2014 Anti-inflammatory and anti-atherogenic properties of adiponectin. Biochimie 94: 2137–2142.Google Scholar
  56. 56.
    Dunmore SJ, Brown JE, 2013 The role of adipokines in beta-cell failure of type 2 diabetes. J Endocrinol 216: T37–45.PubMedGoogle Scholar
  57. 57.
    Kubota N, Yano W, Kubota F, et al, 2007 Adiponectin stimulates AMPactivated protein kinase in the hypothalamus and increases food intake. Cell Metab 6: 55–68.PubMedGoogle Scholar
  58. 58.
    Turer AT, Scherer PE, 2012 Adiponectin: mechanistic insights and clinical implications. Diabetologia 55: 2319–2326.PubMedGoogle Scholar
  59. 59.
    Hotta K, Funahashi F, Arita Y, et al, 2000 Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 20: 1595–1599.PubMedPubMedCentralGoogle Scholar
  60. 60.
    Gutman G, Barak V, Maslovitz S, Amit A, Lessing JB, Geva E, 2009 Recombinant luteinizing hormone induces increased production of ovarian follicular adiponectin in vivo: implications for enhanced insulin sensitivity. Fertil Steril 91: 1837–1841.PubMedGoogle Scholar
  61. 61.
    Chabrolle C, Fosca L, Crochet S, Fesseraud S, Dupont J, 2007 Expression of adiponectin and its receptors (AdipoR1 and AdipoR2) in chicken ovary: potential role in ovarian steroidogenesis. Domest Anim Endocrinol 33: 480–487.PubMedGoogle Scholar
  62. 62.
    Wickham EP3rd, Tao T, Nestler JE, McGee EA, 2014 Activation of the LH receptor up regulates the type 2 adiponectin receptor in human granulosa cells. J Assist Reprod Genet 30: 963–968.Google Scholar
  63. 63.
    Pierre P, Froment P, Negre D, et al, 2009 Role of adiponectin receptors, AdipoR1 and AdipoR2, in the steroidogenesis of the human granulosa tumor cell line, KGN. Hum Reprod 24: 2890–2901.PubMedGoogle Scholar
  64. 64.
    Bertoldo MJ, Faure M, Dupont J, Froment P, 2014 AMPK: a master energy regulator for gonadal function. Front Neurosci 9: 235.Google Scholar
  65. 65.
    Tosca L, Rame C, Chabrolle C, Tesseraud S, Dupont J, 2013 Metformin decreases IGF1-induced cell proliferation and protein synthesis through AMP-activated protein kinase in cultured bovine granulosa cells. Reproduction 139: 409–418.Google Scholar
  66. 66.
    Mu YM, Yanase T, Nishi Y, et al, 2001 Saturated FFAs, palmitic acid and stearic acid, induce apoptosis in human granulosa cells. Endocrinology 142: 3590–3597.PubMedGoogle Scholar
  67. 67.
    Jungheim ES, Macones GA, Odem RR, et al, 2014 Associations between free fatty acids, cumulus oocyte complex morphology and ovarian function during in vitro fertilization. Fertil Steril 95: 1970–1974.Google Scholar
  68. 68.
    Kawwass JF, Summer R, Kallen CB, 2014 Direct effects of leptin and adiponectin on peripheral reproductive tissues: a critical review. Mol Hum Reprod 21: 617–632.Google Scholar
  69. 69.
    Campos DB, Palin MF, Bordignon V, Murphy BD, 2008 The ‘beneficial’ adipokines in reproduction and fertility. Int J Obes (Lond)32: 223–231.Google Scholar
  70. 70.
    Jungheim ES, Schoeller EL, Marquard KL, Louden ED, Schaffer JE, Moley KH, 2013 Diet-induced obesity model: abnormal oocytes and persistent growth abnormalities in the offspring. Endocrinology 151: 4039–4046.Google Scholar
  71. 71.
    Igosheva N, Abramov AY, Poston L, et al, 2014 Maternal diet-induced obesity alters mitochondrial activity and redox status in mouse oocytes and zygotes. PLoS One 5: e10074.Google Scholar
  72. 72.
    Wu LL, Dunning KR, Yang X, et al, 2013 High-fat diet causes lipotoxicity responses in cumulus-oocyte complexes and decreased fertilization rates. Endocrinology 151: 5438–5445.Google Scholar
  73. 73.
    Palin MF, Bordignon VV, Murphy BD, 2014, Adiponectin and the control of female reproductive functions. Vitam Horm 90: 239–287.Google Scholar
  74. 74.
    Tabandeh MR, Golestani N, Kafi M, Hosseini A, Saeb M, Sarkoohi P, 2015 Gene expression pattern of adiponectin and adiponectin receptors in dominant and atretic follicles and oocytes screened based on brilliant cresyl blue staining. Anim Reprod Sci 131: 30–40.Google Scholar
  75. 75.
    Mansour M, Coleman E, Dennis J, et al, 2009 Activation of PPARy by Rosiglitazone does not negatively impact male sex steroid hormones in diabetic rats. PPAR Res 2009: 101857.PubMedPubMedCentralGoogle Scholar
  76. 76.
    Chabrolle C, Tosca L, Rame C, Lecomte P, Royere D, Dupont J, 2009 Adiponectin increases insulin-like growth factor I-induced progesterone and estradiol secretion in human granulosa cells. Fertil Steril 92: 1988–1996.PubMedGoogle Scholar
  77. 77.
    Fukuhara A, Matsuda M, Nishizawa M, et al, 2005 Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 307: 426–430.PubMedGoogle Scholar
  78. 78.
    El-Mesallamy HO, Kassem DH, El-Demerdash E, Amin AI, 2013 Vaspin and visfatin/Nampt are interesting interrelated adipokines playing a role in the pathogenesis of type 2 diabetes mellitus. Metabolism 60: 63–70.Google Scholar
  79. 79.
    Panidis D, Farmakiotis D, Rousso D, et al, 2008 Plasma visfatin levels in normal weight women with polycystic ovary syndrome. Eur J Intern Med 19: 406–412.PubMedGoogle Scholar
  80. 80.
    Shen CJ, Tsai EM, Lee JN, Chen YL, Lee CH, Chan TF, 2013, The concentrations of visfatin in the follicular fluids of women undergoing controlled ovarian stimulation are correlated to the number of oocytes retrieved. Fertil Steril 93: 1844–1850.Google Scholar
  81. 81.
    Reverchon M, Cornuau M, Cloix L, et al, 2015 Visfatin is expressed in human granulosa cells: regulation by metformin through AMPK/SIRT1 pathways and its role in steroidogenesis. Mol Hum Reprod 19: 313–326.Google Scholar
  82. 82.
    Rak A, Drwal E, Karpeta A, Gregoraszczuk EL, 2015 Regulatory Role of Gonadotropins and Local Factors Produced by Ovarian Follicles on In Vitro Resistin Expression and Action on Porcine Follicular Steroidogenesis. Biology of reproduction 92: 142.PubMedGoogle Scholar
  83. 83.
    Chu Y, Cui Q, Feng G, Song Z, Jiang X, 2009 The expression of resistin in adipose tissues of patients with polycystic ovary syndrome and insulin resistance. J Huazhong Univ Sci Technolog Med Sci 29: 642–645.PubMedGoogle Scholar
  84. 84.
    Olszanecka-Glinianowicz M, Kuglin D, Dabkowska-Huc A, Skalba P, 2013, Serum adiponectin and resistin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 154: 51–56.Google Scholar
  85. 85.
    Goralski KB, McCarthy TC, Hanniman EA, et al, 2007 Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism. J Biol Chem 282: 28175–28188.PubMedGoogle Scholar
  86. 86.
    Ernst MC, Issa M, Goralski KB, Sinal CJ, 2014 Chemerin exacerbates glucose intolerance in mouse models of obesity and diabetes. Endocrinology 151: 1998–2007.Google Scholar
  87. 87.
    Catalan V, Gomez-Ambrosi J, Rodriguez A, et al, 2014 Increased levels of chemerin and its receptor, chemokine-like receptor-1, in obesity are related to inflammation: tumor necrosis factor-alpha stimulates mRNA levels of chemerin in visceral adipocytes from obese patients. Surg Obes Relat Dis 9: 306–314.Google Scholar
  88. 88.
    Hart R, Greaves DR, 2014, Chemerin contributes to inflammation by promoting macrophage adhesion to VCAM-1 and fibronectin through clustering of VLA-4 and VLA-5. J Immunol 185: 3728–3739.Google Scholar
  89. 89.
    Lehrke M, Becker A, Greif M, et al, 2009 Chemerin is associated with markers of inflammation and components of the metabolic syndrome but does not predict coronary atherosclerosis. Eur J Endocrinol 161: 339–344.PubMedGoogle Scholar
  90. 90.
    Yu S, Zhang Y, Li MZ, et al, 2015 Chemerin and apelin are positively correlated with inflammation in obese type 2 diabetic patients. Chin Med J (Engl) 125: 3440–3444.Google Scholar
  91. 91.
    Reverchon M, Bertoldo MJ, Rame C, Froment P, Dupont J, 2015 CHEMERIN (RARRES2) decreases in vitro granulosa cell steroidogenesis and blocks oocyte meiotic progression in bovine species. Biol Reprod 90: 102.Google Scholar
  92. 92.
    Wang Q, Kim JY, Xue K, Liu JY, Leader A, Tsang BK, 2015 Chemerin, a novel regulator of follicular steroidogenesis and its potential involvement in polycystic ovarian syndrome. Endocrinology 153: 5600–5611.Google Scholar
  93. 93.
    Reverchon M, Cornuau M, Rame C, Guerif F, Royere D, Dupont J, 2015 Chemerin inhibits IGF-1-induced progesterone and estradiol secretion in human granulosa cells. Hum Reprod 27: 1790–1800.Google Scholar
  94. 94.
    Spicer LJ, Schreiber NB, Lagaly DV, Aad PY, Douthit LB, Grado-Ahuir JA, 2015 Effect of resistin on granulosa and theca cell function in cattle. Anim Reprod Sci 124: 19–27.Google Scholar
  95. 95.
    Bozaoglu K, Bolton K, McMillan J, et al, 2007 Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology 148: 4687–4694.PubMedGoogle Scholar
  96. 96.
    Tan BK, Chen J, Farhatullah S, et al, 2009 Insulin and metformin regulate circulating and adipose tissue chemerin. Diabetes 58: 1971–1977.PubMedPubMedCentralGoogle Scholar
  97. 97.
    Rato L, Alves MG, Cavaco JE, Oliveira PF, 2014 High-energy diets: a threat for male fertility? Obes Rev 15: 996–1007.PubMedGoogle Scholar
  98. 98.
    Mah PM, Wittert GA, 2015 Obesity and testicular function. Mol Cell Endocrinol 316: 180–186.Google Scholar
  99. 99.
    Schulte DM, Hahn M, Oberhauser F, et al, 2014 Caloric restriction increases serum testosterone concentrations in obese male subjects by two distinct mechanisms. Horm Metab Res 46: 283–286.PubMedGoogle Scholar
  100. 100.
    Wu L, Xu B, Fan W, Zhu X, Wang G, Zhang A, 2015 Adiponectin protects Leydig cells against proinflammatory cytokines by suppressing the nuclear factor-kappaB signaling pathway. Febs J 280: 3920–3927.Google Scholar
  101. 101.
    Hameed W, Yousaf I, Latif R, Aslam M, 2014 Effect of visfatin on testicular steroidogenesis in purified Leydig cells. J Ayub Med Coll Abbottabad 24: 62–64.Google Scholar
  102. 102.
    Dermitzaki E, Liapakis G, Androulidaki A, et al, 2014 Corticotrophin-Releasing Factor (CRF) and the urocortins are potent regulators of the inflammatory phenotype of human and mouse white adipocytes and the differentiation of mouse 3T3L1 pre-adipocytes. PLoS One 9: e97060.PubMedPubMedCentralGoogle Scholar
  103. 103.
    Kalra SP, Dube MG, Pu S, Xu B, Horvath TL, Kalra PS, 1999 Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr Rev 200: 68–100.Google Scholar
  104. 104.
    Taghavi SA, Ashrafi M, Mehdizadeh M, Karimian L, Joghataie MT, Aflatoonian R, 2014 Toll-like receptors expression in follicular cells of patients with poor ovarian response. Int J Fertil Steril 8: 183–192.PubMedPubMedCentralGoogle Scholar
  105. 105.
    An LF, Zhang XH, Sun XT, Zhao LH, Li S, Wang WH, 2015 Unexplained infertility patients have increased serum IL-2, IL-4, IL-6, IL-8, IL-21, TNF a, IFNy and increased Tfh/CD4 T cell ratio: increased Tfh and IL-21 strongly correlate with presence of autoantibodies. Immunol Invest 44: 164–173.PubMedGoogle Scholar
  106. 106.
    Lotti F, Corona G, Mondaini N, et al, 2014 Seminal, clinical and colour-Doppler ultrasound correlations of prostatitis-like symptoms in males of infertile couples. Andrology 2: 30–41.PubMedGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2015

Authors and Affiliations

  • Christos Tsatsanis
    • 1
  • Eirini Dermitzaki
    • 1
  • Pavlina Avgoustinaki
    • 1
  • Niki Malliaraki
    • 1
  • Vasilis Mytaras
    • 1
  • Andrew N. Margioris
    • 1
  1. 1.Department of Clinical Chemistry, School of MedicineUniversity of CreteHeraklionGreece

Personalised recommendations