Roles of leptin, adiponectin and resistin in the transcriptional regulation of steroidogenic genes contributing to decreased Leydig cells function in obesity

References

1. Pi-Sunyer FX. The obesity epidemic: pathophysiology and consequences of obesity. Obes Res 2002;10(Suppl 2):97S–104S.10.1038/oby.2002.202Suche in Google Scholar

2. Gray A, Feldman HA, McKinlay JB, Longcope C. Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab 1991;73:1016–25.10.1210/jcem-73-5-1016Suche in Google Scholar

3. Cohen PG. Aromatase, adiposity, aging and disease. The hypogonadal-metabolic-atherogenic-disease and aging connection. Med Hypotheses 2001;56:702–8.10.1054/mehy.2000.1169Suche in Google Scholar

4. Mårin P, Arver S. Androgens and abdominal obesity. Baillières Clin Endocrinol Metab 1998;12:441–51.10.1016/S0950-351X(98)80191-2Suche in Google Scholar

5. De Maddalena C, Vodo S, Petroni A, Aloisi AM. Impact of testosterone on body fat composition. J Cell Physiol 2012;227:3744–8.10.1002/jcp.24096Suche in Google Scholar PubMed

6. Xu X, De Pergola G, Björntorp P. The effects of androgens on the regulation of lipolysis in adipose precursor cells. Endocrinology 1990;126:1229–34.10.1210/endo-126-2-1229Suche in Google Scholar PubMed

7. Mårin P. Testosterone and regional fat distribution. Obes Res 1995;3(Suppl 4):609S–12S.10.1002/j.1550-8528.1995.tb00233.xSuche in Google Scholar PubMed

8. Pardo M, Roca-Rivada A, Seoane LM, Casanueva FF. Obesidomics: contribution of adipose tissue secretome analysis to obesity research. Endocrine 2012;41:374–83.10.1007/s12020-012-9617-zSuche in Google Scholar PubMed

9. Marinou K, Tousoulis D, Antonopoulos AS, Stefanadi E, Stefanadis C. Obesity and cardiovascular disease: from pathophysiology to risk stratification. Int J Cardiol 2010;138:3–8.10.1016/j.ijcard.2009.03.135Suche in Google Scholar PubMed

10. Rabe K, Lehrke M, Parhofer KG, Broedl UC. Adipokines and insulin resistance. Mol Med 2008;14:741–51.10.2119/2008-00058.RabeSuche in Google Scholar PubMed PubMed Central

11. Hutcheson J. Adipokines influence the inflammatory balance in autoimmunity. Cytokine 2015;75:272–9.10.1016/j.cyto.2015.04.004Suche in Google Scholar PubMed

12. Cohen PG. The hypogonadal-obesity cycle: role of aromatase in modulating the testosterone-estradiol shunt – a major factor in the genesis of morbid obesity. Med Hypotheses 1999;52:49–51.10.1054/mehy.1997.0624Suche in Google Scholar PubMed

13. Kley HK, Solbach HG, McKinnan JC, Krüskemper HL. Testosterone decrease and oestrogen increase in male patients with obesity. Acta Endocrinol 1979;91:553–63.10.1530/acta.0.0910553Suche in Google Scholar PubMed

14. Zumoff B, Strain GW, Miller LK, Rosner W, Senie R, Seres DS, Rosenfeld RS. Plasma free and non-sex-hormone-binding-globulin-bound testosterone are decreased in obese men in proportion to their degree of obesity. J Clin Endocrinol Metab 1990;71:929–31.10.1210/jcem-71-4-929Suche in Google Scholar PubMed

15. Vermeulen A. Decreased androgen levels and obesity in men. Ann Med 1996;28:13–5.10.3109/07853899608999068Suche in Google Scholar PubMed

16. Vermeulen A, Kaufman JM. Ageing of the hypothalamo-pituitary-testicular axis in men. Horm Res 1995;43:25–8.10.1159/000184233Suche in Google Scholar PubMed

17. Teerds KJ, de Rooij DG, Keijer J. Functional relationship between obesity and male reproduction: from humans to animal models. Hum Reprod Update 2011;17:667–83.10.1093/humupd/dmr017Suche in Google Scholar PubMed

18. Strobel A, Issad T, Camoin L, Ozata M, Strosberg AD. A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet 1998;18:213–5.10.1038/ng0398-213Suche in Google Scholar PubMed

19. Ozata M, Ozdemir IC, Licinio J. Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. J Clin Endocrinol Metab 1999;84:3686–95.10.1210/jcem.84.10.5999Suche in Google Scholar PubMed

20. Clément K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, Gourmelen M, Dina C, Chambaz J, Lacorte JM, Basdevant A, Bougnères P, Lebouc Y, Froguel P, Guy-Grand B. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 1998;392:398–401.10.1038/32911Suche in Google Scholar PubMed

21. Mounzih K, Lu R, Chehab FF. Leptin treatment rescues the sterility of genetically obese ob/ob males. Endocrinology 1997;138:1190–3.10.1210/endo.138.3.5024Suche in Google Scholar PubMed

22. Chehab FF, Lim ME, Lu R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet 1996;12:318–20.10.1038/ng0396-318Suche in Google Scholar PubMed

23. 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 Endocrinol Metab 1999;84:3673–80.10.1210/jcem.84.10.6082Suche in Google Scholar

24. 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.xSuche in Google Scholar PubMed

25. Aquila S, Gentile M, Middea E, Catalano S, Morelli C, Pezzi V, Andò S. Leptin secretion by human ejaculated spermatozoa. J Clin Endocrinol Metab 2005;90:4753–61.10.1210/jc.2004-2233Suche in Google Scholar PubMed

26. 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.20796Suche in Google Scholar PubMed

27. Chen B, Guo J-H, Lu Y-N, Ying X-L, Hu K, Xiang Z-Q, Wang Y-X, Chen P, Huang Y-R. Leptin and varicocele-related spermatogenesis dysfunction: animal experiment and clinical study. Int J Androl 2009;32:532–41.10.1111/j.1365-2605.2008.00892.xSuche in Google Scholar PubMed

28. 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.20880Suche in Google Scholar PubMed

29. Aquila S, Rago V, Guido C, Casaburi I, Zupo S, Carpino A. Leptin and leptin receptor in pig spermatozoa: evidence of their involvement in sperm capacitation and survival. Reprod 2008;136:23–32.10.1530/REP-07-0304Suche in Google Scholar PubMed

30. Jope T, Lammert A, Kratzsch J, Paasch U, Glander H-J. 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.xSuche in Google Scholar PubMed

31. El-Hefnawy T, Ioffe S, Dym M. Expression of the leptin receptor during germ cell development in the mouse testis. Endocrinology 2000;141:2624–30.10.1210/endo.141.7.7542Suche in Google Scholar PubMed

32. De Matteis R, Dashtipour K, Ognibene A, Cinti S. Localization of leptin receptor splice variants in mouse peripheral tissues by immunohistochemistry. Proc Nutr Soc 1998;57:441–8.10.1079/PNS19980063Suche in Google Scholar PubMed

33. Caprio M, Fabbrini E, Ricci G, Basciani S, Gnessi L, Arizzi M, Carta AR, De Martino MU, Isidori AM, Frajese GV, Fabbri A. Ontogenesis of leptin receptor in rat Leydig cells. Biol Reprod 2003;68:1199–207.10.1095/biolreprod.102.007831Suche in Google Scholar PubMed

34. 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.140.11.7088Suche in Google Scholar PubMed

35. Tena-Sempere M, Manna PR, Zhang FP, Pinilla L, González LC, Diéguez 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.0.1700413Suche in Google Scholar PubMed

36. Fombonne J, Charrier C, Goddard I, Moyse E, Krantic S. Leptin-mediated decrease of cyclin A2 and increase of cyclin D1 expression: relevance for the control of prepubertal rat Leydig cell division and differentiation. Endocrinology 2007;148:2126–37.10.1210/en.2006-1218Suche in Google Scholar PubMed

37. Abavisani A, Baghbanzadeh A, Shayan P, Dehghani H. Leptin mRNA in bovine spermatozoa. Res Vet Sci 2011;90:439–42.10.1016/j.rvsc.2010.07.009Suche in Google Scholar PubMed

38. Nikbakht G, Mehr MR, Baghbanzadeh A, Tajik P, Tamanini C, Emam M. Leptin receptor mRNA in bull ejaculated spermatozoa. Reprod Domest Anim 2010;45:237–42.10.1111/j.1439-0531.2008.01247.xSuche in Google Scholar PubMed

39. Caminos JE, Nogueiras R, Gaytòn F, Pineda R, Gonzòlez CR, Barreiro ML, Castaño JP, Malagón MM, Pinilla L, Toppari J, Diéguez C, Tena-Sempere M. Novel expression and direct effects of adiponectin in the rat testis. Endocrinology 2008;149:3390–402.10.1210/en.2007-1582Suche in Google Scholar PubMed

40. Kasimanickam VR, Kasimanickam RK, Kastelic JP, Stevenson JS. Associations of adiponectin and fertility estimates in Holstein bulls. Theriogenology 2013;79:766–77.e1–3.10.1016/j.theriogenology.2012.12.001Suche in Google Scholar PubMed

41. Ocón-Grove OM, Krzysik-Walker SM, Maddineni SR, Hendricks GL 3rd, Ramachandran R. Adiponectin and its receptors are expressed in the chicken testis: influence of sexual maturation on testicular ADIPOR1 and ADIPOR2 mRNA abundance. Reprod 2008;136:627–38.10.1530/REP-07-0446Suche in Google Scholar PubMed

42. Ramachandran R, Maddineni S, Ocón-Grove O, Hendricks G 3rd, Vasilatos-Younken R, Hadley JA. Expression of adiponectin and its receptors in avian species. Gen Comp Endocrinol 2013;190:88–95.10.1016/j.ygcen.2013.05.004Suche in Google Scholar

43. Wu L, Xu B, Fan W, Zhu X, Wang G, Zhang A. Adiponectin protects Leydig cells against proinflammatory cytokines by suppressing the nuclear factor-κB signaling pathway. FEBS J 2013;280:3920–7.10.1111/febs.12391Suche in Google Scholar

44. Jean S, Landry D, Daigle M, Martin LJ. Influence of the adipose derived hormone resistin on STAT factors, steroidogenesis and proliferation of Leydig cells. Asian Pac J Reprod 2012;1:1–6.10.1016/S2305-0500(13)60038-XSuche in Google Scholar

45. Nogueiras R, Barreiro ML, Caminos JE, Gaytòn F, Suominen JS, Navarro VM, Casanueva FF, Aguilar E, Toppari J, Diéguez C, Tena-Sempere M. Novel expression of resistin in rat testis: functional role and regulation by nutritional status and hormonal factors. J Cell Sci 2004;117:3247–57.10.1242/jcs.01196Suche in Google Scholar

46. Landry D, Cloutier F, Martin LJ. Implications of leptin in neuroendocrine regulation of male reproduction. Reprod Biol 2013;13:1–14.10.1016/j.repbio.2012.12.001Suche in Google Scholar

47. Prolo P, Wong M-L, Licinio J. Leptin. Int J Biochem Cell Biol 1998;30:1285–90.10.1016/S1357-2725(98)00094-6Suche in Google Scholar

48. Bado A, Levasseur S, Attoub S, Kermorgant S, Laigneau JP, Bortoluzzi MN, Moizo L, Lehy T, Guerre-Millo M, Le Marchand-Brustel Y, Lewin MJ. The stomach is a source of leptin. Nature 1998;394:790–3.10.1038/29547Suche in Google Scholar PubMed

49. Wang J, Liu R, Hawkins M, Barzilai N, Rossetti L. A nutrient-sensing pathway regulates leptin gene expression in muscle and fat. Nature 1998;393:684–8.10.1038/31474Suche in Google Scholar PubMed

50. 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.E1099Suche in Google Scholar PubMed

51. Cunningham MJ, Clifton DK, Steiner RA. Leptin’s actions on the reproductive axis: perspectives and mechanisms. Biol Reprod 1999;60:216–22.10.1095/biolreprod60.2.216Suche in Google Scholar PubMed

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

53. Tartaglia LA. The leptin receptor. J Biol Chem 1997;272:6093–6.10.1074/jbc.272.10.6093Suche in Google Scholar PubMed

54. Lammert A, Kiess W, Bottner A, Glasow A, Kratzsch J. Soluble leptin receptor represents the main leptin binding activity in human blood. Biochem Biophys Res Commun 2001;283:982–8.10.1006/bbrc.2001.4885Suche in Google Scholar PubMed

55. Margetic S, Gazzola C, Pegg GG, Hill RA. Leptin: a review of its peripheral actions and interactions. Int J Obes Relat Metab Disord 2002;26:1407–33.10.1038/sj.ijo.0802142Suche in Google Scholar PubMed

56. Kloek C, Haq AK, Dunn SL, Lavery HJ, Banks AS, Myers MG Jr. Regulation of Jak kinases by intracellular leptin receptor sequences. J Biol Chem 2002;277:41547–55.10.1074/jbc.M205148200Suche in Google Scholar PubMed

57. Villanueva EC, Myers MG Jr. Leptin receptor signaling and the regulation of mammalian physiology. Int J Obes 2008;32(Suppl 7): S8–12.10.1038/ijo.2008.232Suche in Google Scholar PubMed PubMed Central

58. Banks AS, Davis SM, Bates SH, Myers MG Jr. Activation of downstream signals by the long form of the leptin receptor. J Biol Chem 2000;275:14563–72.10.1074/jbc.275.19.14563Suche in Google Scholar PubMed

59. Baumann H, Morella KK, White DW, Dembski M, Bailon PS, Kim H, Lai CF, Tartaglia LA. The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors. Proc Natl Acad Sci USA 1996;93:8374–8.10.1073/pnas.93.16.8374Suche in Google Scholar PubMed PubMed Central

60. White DW, Kuropatwinski KK, Devos R, Baumann H, Tartaglia LA. Leptin receptor (OB-R) signaling. Cytoplasmic domain mutational analysis and evidence for receptor homo-oligomerization. J Biol Chem 1997;272:4065–71.10.1074/jbc.272.7.4065Suche in Google Scholar PubMed

61. Schindler C, Darnell JE Jr. Transcriptional responses to polypeptide ligands: the JAK-STAT pathway. Annu Rev Biochem 1995;64:621–51.10.1146/annurev.bi.64.070195.003201Suche in Google Scholar PubMed

62. Bates SH, Stearns WH, Dundon TA, Schubert M, Tso AW, Wang Y, Banks AS, Lavery HJ, Haq AK, Maratos-Flier E, Neel BG, Schwartz MW, Myers MG Jr. STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature 2003;421:856–9.10.1038/nature01388Suche in Google Scholar

63. Bjorbak C, Lavery HJ, Bates SH, Olson RK, Davis SM, Flier JS, Myers MG Jr. SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985. J Biol Chem 2000;275:40649–57.10.1074/jbc.M007577200Suche in Google Scholar

64. Oswal A, Yeo G. Leptin and the control of body weight: a review of its diverse central targets, signaling mechanisms, and role in the pathogenesis of obesity. Obes 2010;18:221–9.10.1038/oby.2009.228Suche in Google Scholar

65. Myers MG, Cowley MA, Münzberg H. Mechanisms of leptin action and leptin resistance. Annu Rev Physiol 2008;70:537–56.10.1146/annurev.physiol.70.113006.100707Suche in Google Scholar

66. Carpenter LR, Farruggella TJ, Symes A, Karow ML, Yancopoulos GD, Stahl N. Enhancing leptin response by preventing SH2-containing phosphatase 2 interaction with Ob receptor. Proc Natl Acad Sci USA 1998;95:6061–6.10.1073/pnas.95.11.6061Suche in Google Scholar

67. Li C, Friedman JM. Leptin receptor activation of SH2 domain containing protein tyrosine phosphatase 2 modulates Ob receptor signal transduction. Proc Natl Acad Sci USA 1999;96:9677–82.10.1073/pnas.96.17.9677Suche in Google Scholar

68. Zabeau L, Lavens D, Peelman F, Eyckerman S, Vandekerckhove J, Tavernier J. The ins and outs of leptin receptor activation. FEBS Lett 2003;546:45–50.10.1016/S0014-5793(03)00440-XSuche in Google Scholar

69. Bjørbaek C, Buchholz RM, Davis SM, Bates SH, Pierroz DD, Gu H, Neel BG, Myers MG Jr, Flier JS. Divergent roles of SHP-2 in ERK activation by leptin receptors. J Biol Chem 2001;276:4747–55.10.1074/jbc.M007439200Suche in Google Scholar PubMed

70. Gao Q, Horvath TL. Cross-talk between estrogen and leptin signaling in the hypothalamus. Am J Physiol Endocrinol Metab 2008;294:E817–26.10.1152/ajpendo.00733.2007Suche in Google Scholar PubMed

71. Kim YB, Uotani S, Pierroz DD, Flier JS, Kahn BB. In vivo administration of leptin activates signal transduction directly in insulin-sensitive tissues: overlapping but distinct pathways from insulin. Endocrinology 2000;141:2328–39.10.1210/endo.141.7.7536Suche in Google Scholar PubMed

72. Minokoshi Y, Kim Y-B, Peroni OD, Fryer LG, Müller C, Carling D, Kahn BB. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 2002;415:339–43.10.1038/415339aSuche in Google Scholar PubMed

73. Lim CT, Kola B, Korbonits M. AMPK as a mediator of hormonal signalling. J Mol Endocrinol 2010;44:87–97.10.1677/JME-09-0063Suche in Google Scholar PubMed

74. Séverin S, Ghevaert C, Mazharian A. The mitogen-activated protein kinase signaling pathways: role in megakaryocyte differentiation. J Thromb Haemost 2010;8:17–26.10.1111/j.1538-7836.2009.03658.xSuche in Google Scholar PubMed

75. Sharma V, Mustafa S, Patel N, Wambolt R, Allard MF, McNeill JH. Stimulation of cardiac fatty acid oxidation by leptin is mediated by a nitric oxide-p38 MAPK-dependent mechanism. Eur J Pharmacol 2009;617:113–7.10.1016/j.ejphar.2009.06.037Suche in Google Scholar PubMed

76. Batarseh A, Li J, Papadopoulos V. Protein kinase C epsilon regulation of translocator protein (18 kDa) Tspo gene expression is mediated through a MAPK pathway targeting STAT3 and c-Jun transcription factors. Biochemistry (Mosc) 2010;49:4766–78.10.1021/bi100020eSuche in Google Scholar PubMed PubMed Central

77. Du K, Montminy M. CREB is a regulatory target for the protein kinase Akt/PKB. J Biol Chem 1998;273:32377–9.10.1074/jbc.273.49.32377Suche in Google Scholar PubMed

78. Pekarsky Y, Hallas C, Palamarchuk A, Koval A, Bullrich F, Hirata Y, Bichi R, Letofsky J, Croce CM. Akt phosphorylates and regulates the orphan nuclear receptor Nur77. Proc Natl Acad Sci USA 2001;98:3690–4.10.1073/pnas.051003198Suche in Google Scholar PubMed PubMed Central

79. Abdou HS, Bergeron F, Tremblay JJ. A cell-autonomous molecular cascade initiated by AMP-activated protein kinase represses steroidogenesis. Mol Cell Biol 2014;34:4257–71.10.1128/MCB.00734-14Suche in Google Scholar PubMed PubMed Central

80. Li Y, Xu S, Mihaylova MM, Zheng B, Hou X, Jiang B, Park O, Luo Z, Lefai E, Shyy JY, Gao B, Wierzbicki M, Verbeuren TJ, Shaw RJ, Cohen RA, Zang M. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab 2011;13:376–88.10.1016/j.cmet.2011.03.009Suche in Google Scholar PubMed PubMed Central

81. Shea-Eaton WK, Trinidad MJ, Lopez D, Nackley A, McLean MP. Sterol regulatory element binding protein-1a regulation of the steroidogenic acute regulatory protein gene. Endocrinology 2001;142:1525–33.10.1210/endo.142.4.8075Suche in Google Scholar PubMed

82. Christenson LK, Osborne TF, McAllister JM, Strauss JF. Conditional response of the human steroidogenic acute regulatory protein gene promoter to sterol regulatory element binding protein-1a. Endocrinology 2001;142:28–36.10.1210/endo.142.1.7867Suche in Google Scholar PubMed

83. Matzkin ME, Yamashita S, Ascoli M. The ERK1/2 pathway regulates testosterone synthesis by coordinately regulating the expression of steroidogenic genes in Leydig cells. Mol Cell Endocrinol 2013;370:130–7.10.1016/j.mce.2013.02.017Suche in Google Scholar PubMed PubMed Central

84. Monje P, Marinissen MJ, Gutkind JS. Phosphorylation of the carboxyl-terminal transactivation domain of c-Fos by extracellular signal-regulated kinase mediates the transcriptional activation of AP-1 and cellular transformation induced by platelet-derived growth factor. Mol Cell Biol 2003;23:7030–43.10.1128/MCB.23.19.7030-7043.2003Suche in Google Scholar PubMed PubMed Central

85. Gupta S, Barrett T, Whitmarsh AJ, Cavanagh J, Sluss HK, Dérijard B, Davis RJ. Selective interaction of JNK protein kinase isoforms with transcription factors. EMBO J 1996;15:2760–70.10.1002/j.1460-2075.1996.tb00636.xSuche in Google Scholar

86. Zhao M, New L, Kravchenko VV, Kato Y, Gram H, di Padova F, Olson EN, Ulevitch RJ, Han J. Regulation of the MEF2 family of transcription factors by p38. Mol Cell Biol 1999;19:21–30.10.1128/MCB.19.1.21Suche in Google Scholar PubMed PubMed Central

87. Ramakrishnan V, Pace BS. Regulation of γ-globin gene expression involves signaling through the p38 MAPK/CREB1 pathway. Blood Cells Mol Dis 2011;47:12–22.10.1016/j.bcmd.2011.03.003Suche in Google Scholar PubMed PubMed Central

88. Manna PR, Dyson MT, Stocco DM. Regulation of the steroidogenic acute regulatory protein gene expression: present and future perspectives. Mol Hum Reprod 2009;15:321–33.10.1093/molehr/gap025Suche in Google Scholar PubMed PubMed Central

89. Manna PR, Wang X-J, Stocco DM. Involvement of multiple transcription factors in the regulation of steroidogenic acute regulatory protein gene expression. Steroids 2003;68:1125–34.10.1016/j.steroids.2003.07.009Suche in Google Scholar PubMed

90. Levy DE, Darnell JE. Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol 2002;3:651–62.10.1038/nrm909Suche in Google Scholar PubMed

91. Ruiz-Cortés ZT, Martel-Kennes Y, Gévry NY, Downey BR, Palin M-F, Murphy BD. Biphasic effects of leptin in porcine granulosa cells. Biol Reprod 2003;68:789–96.10.1095/biolreprod.102.010702Suche in Google Scholar PubMed

92. Simard J, Ricketts M-L, Gingras S, Soucy P, Feltus FA, Melner MH. Molecular biology of the 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase gene family. Endocr Rev 2005;26:525–82.10.1210/er.2002-0050Suche in Google Scholar

93. Frühbeck G. Intracellular signalling pathways activated by leptin. Biochem J 2006;393:7–20.10.1042/BJ20051578Suche in Google Scholar

94. Roy VK, Krishna A. Role of leptin in seasonal adiposity associated changes in testicular activity of vespertilionid bat, Scotophilus heathi. Gen Comp Endocrinol 2010;168:160–8.10.1016/j.ygcen.2010.04.023Suche in Google Scholar

95. Gong Y, Ishida-Takahashi R, Villanueva EC, Fingar DC, Münzberg H, Myers MG Jr. The long form of the leptin receptor regulates STAT5 and ribosomal protein S6 via alternate mechanisms. J Biol Chem 2007;282:31019–27.10.1074/jbc.M702838200Suche in Google Scholar

96. Mütze J, Roth J, Gerstberger R, Hübschle T. Nuclear translocation of the transcription factor STAT5 in the rat brain after systemic leptin administration. Neurosci Lett 2007;417:286–91.10.1016/j.neulet.2007.02.074Suche in Google Scholar

97. Bendinelli P, Maroni P, Pecori Giraldi F, Piccoletti R. Leptin activates Stat3, Stat1 and AP-1 in mouse adipose tissue. Mol Cell Endocrinol 2000;168:11–20.10.1016/S0303-7207(00)00313-0Suche in Google Scholar

98. Martin LJ, Tremblay JJ. The nuclear receptors NUR77 and SF1 play additive roles with c-JUN through distinct elements on the mouse Star promoter. J Mol Endocrinol 2009;42:119–29.10.1677/JME-08-0095Suche in Google Scholar

99. O’Shea EK, Rutkowski R, Kim PS. Mechanism of specificity in the Fos-Jun oncoprotein heterodimer. Cell 1992;68:699–708.10.1016/0092-8674(92)90145-3Suche in Google Scholar

100. Machinal-Quélin F, Dieudonné MN, Leneveu MC, Pecquery R, Giudicelli Y. Proadipogenic effect of leptin on rat preadipocytes in vitro: activation of MAPK and STAT3 signaling pathways. Am J Physiol Cell Physiol 2002;282:C853–63.10.1152/ajpcell.00331.2001Suche in Google Scholar PubMed

101. Caüzac M, Czuba D, Girard J, Hauguel-de Mouzon S. Transduction of leptin growth signals in placental cells is independent of JAK-STAT activation. Placenta 2003;24:378–84.10.1053/plac.2002.0915Suche in Google Scholar PubMed

102. Cui H, Cai F, Belsham DD. Leptin signaling in neurotensin neurons involves STAT, MAP kinases ERK1/2, and p38 through c-Fos and ATF1. FASEB J 2006;20:2654–6.10.1096/fj.06-5989fjeSuche in Google Scholar PubMed

103. Shea-Eaton W, Sandhoff TW, Lopez D, Hales DB, McLean MP. Transcriptional repression of the rat steroidogenic acute regulatory (StAR) protein gene by the AP-1 family member c-Fos. Mol Cell Endocrinol 2002;188:161–70.10.1016/S0303-7207(01)00715-8Suche in Google Scholar

104. Manna PR, Stocco DM. Crosstalk of CREB and Fos/Jun on a single cis-element: transcriptional repression of the steroidogenic acute regulatory protein gene. J Mol Endocrinol 2007;39:261–77.10.1677/JME-07-0065Suche in Google Scholar

105. Martin LJ, Bergeron F, Viger RS, Tremblay JJ. Functional cooperation between GATA factors and cJUN on the star promoter in MA-10 Leydig cells. J Androl 2012;33:81–7.10.2164/jandrol.110.012039Suche in Google Scholar

106. Kardassis D, Papakosta P, Pardali K, Moustakas A. c-Jun transactivates the promoter of the human p21(WAF1/Cip1) gene by acting as a superactivator of the ubiquitous transcription factor Sp1. J Biol Chem 1999;274:29572–81.10.1074/jbc.274.41.29572Suche in Google Scholar

107. Lindell K, Bennett PA, Itoh Y, Robinson IC, Carlsson LM, Carlsson B. Leptin receptor 5′untranslated regions in the rat: relative abundance, genomic organization and relation to putative response elements. Mol Cell Endocrinol 2001;172:37–45.10.1016/S0303-7207(00)00382-8Suche in Google Scholar

108. Tsai-Morris CH, Aquilano DR, Dufau ML. Cellular localization of rat testicular aromatase activity during development. Endocrinology 1985;116:38–46.10.1210/endo-116-1-38Suche in Google Scholar PubMed

109. Catalano S, Giordano C, Rizza P, Gu G, Barone I, Bonofiglio D, Giordano F, Malivindi R, Gaccione D, Lanzino M, De Amicis F, Andò S. Evidence that leptin through STAT and CREB signaling enhances cyclin D1 expression and promotes human endometrial cancer proliferation. J Cell Physiol 2009;218:490–500.10.1002/jcp.21622Suche in Google Scholar PubMed

110. Nduati V, Yan Y, Dalmasso G, Driss A, Sitaraman S, Merlin D. Leptin transcriptionally enhances peptide transporter (hPepT1) expression and activity via the cAMP-response element-binding protein and Cdx2 transcription factors. J Biol Chem 2007;282:1359–73.10.1074/jbc.M604267200Suche in Google Scholar PubMed

111. Kim S-G, Lee B, Kim D-H, Kim J, Lee S, Lee S-K, Lee JW. Control of energy balance by hypothalamic gene circuitry involving two nuclear receptors, neuron-derived orphan receptor 1 and glucocorticoid receptor. Mol Cell Biol 2013;33:3826–34.10.1128/MCB.00385-13Suche in Google Scholar PubMed PubMed Central

112. Martin LJ, Tremblay JJ. The human 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase type 2 promoter is a novel target for the immediate early orphan nuclear receptor Nur77 in steroidogenic cells. Endocrinology 2005;146:861–9.10.1210/en.2004-0859Suche in Google Scholar PubMed

113. Martin LJ, Boucher N, Brousseau C, Tremblay JJ. The orphan nuclear receptor NUR77 regulates hormone-induced StAR transcription in Leydig cells through cooperation with Ca2+/calmodulin-dependent protein kinase I. Mol Endocrinol 2008;22:2021–37.10.1210/me.2007-0370Suche in Google Scholar PubMed PubMed Central

114. Gao Y, Li Z, Gabrielsen JS, Simcox JA, Lee S-H, Jones D, Cooksey B, Stoddard G, Cefalu WT, McClain DA. Adipocyte iron regulates leptin and food intake. J Clin Invest 2015;125:3681–91.10.1172/JCI81860Suche in Google Scholar PubMed PubMed Central

115. Altarejos JY, Goebel N, Conkright MD, Inoue H, Xie J, Arias CM, Sawchenko PE, Montminy M. The Creb1 coactivator Crtc1 is required for energy balance and fertility. Nat Med 2008;14:1112–7.10.1038/nm.1866Suche in Google Scholar PubMed PubMed Central

116. Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson Å, Kampf C, Sjöstedt E, Asplund A, Olsson I, Edlund K, Lundberg E, Navani S, Szigyarto CA, Odeberg J, Djureinovic D, Takanen JO, Hober S, Alm T, Edqvist P-H, Berling H, Tegel H, Mulder J, Rockberg J, Nilsson P, Schwenk JM, Hamsten M, von Feilitzen K, Forsberg M, Persson L, Johansson F, Zwahlen M, von Heijne G, Nielsen J, Pontén F. Proteomics. Tissue-based map of the human proteome. Science 2015;347:1260419.10.1126/science.1260419Suche in Google Scholar PubMed

117. Whitby RJ, Stec J, Blind RD, Dixon S, Leesnitzer LM, Orband-Miller LA, Williams SP, Willson TM, Xu R, Zuercher WJ, Cai F, Ingraham HA. Small molecule agonists of the orphan nuclear receptors steroidogenic factor-1 (SF-1, NR5A1) and liver receptor homologue-1 (LRH-1, NR5A2). J Med Chem 2011;54:2266–81.10.1021/jm1014296Suche in Google Scholar PubMed PubMed Central

118. Cao G, Zhao L, Stangl H, Hasegawa T, Richardson JA, Parker KL, Hobbs HH. Developmental and hormonal regulation of murine scavenger receptor, class B, type 1. Mol Endocrinol Baltim Md 1999;13:1460–73.10.1210/mend.13.9.0346Suche in Google Scholar PubMed

119. Mascaró C, Nadal A, Hegardt FG, Marrero PF, Haro D. Contribution of steroidogenic factor 1 to the regulation of cholesterol synthesis. Biochem J 2000;350 Pt 3:785–90.10.1042/bj3500785Suche in Google Scholar

120. Caron KM, Soo SC, Wetsel WC, Stocco DM, Clark BJ, Parker KL. Targeted disruption of the mouse gene encoding steroidogenic acute regulatory protein provides insights into congenital lipoid adrenal hyperplasia. Proc Natl Acad Sci USA 1997;94:11540–5.10.1073/pnas.94.21.11540Suche in Google Scholar PubMed PubMed Central

121. Chau YM, Crawford PA, Woodson KG, Polish JA, Olson LM, Sadovsky Y. Role of steroidogenic-factor 1 in basal and 3′,5′-cyclic adenosine monophosphate-mediated regulation of cytochrome P450 side-chain cleavage enzyme in the mouse. Biol Reprod 1997;57:765–71.10.1095/biolreprod57.4.765Suche in Google Scholar PubMed

122. Leers-Sucheta S, Morohashi K, Mason JI, Melner MH. Synergistic activation of the human type II 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase promoter by the transcription factor steroidogenic factor-1/adrenal 4-binding protein and phorbol ester. J Biol Chem 1997;272:7960–7.10.1074/jbc.272.12.7960Suche in Google Scholar PubMed

123. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 2002;8:1288–95.10.1038/nm788Suche in Google Scholar PubMed

124. Sieminska L, Marek B, Kos-Kudla B, Niedziolka D, Kajdaniuk D, Nowak M, Glogowska-Szelag J. Serum adiponectin in women with polycystic ovarian syndrome and its relation to clinical, metabolic and endocrine parameters. J Endocrinol Invest 2004;27:528–34.10.1007/BF03347474Suche in Google Scholar PubMed

125. Chabrolle C, Tosca L, Dupont J. Regulation of adiponectin and its receptors in rat ovary by human chorionic gonadotrophin treatment and potential involvement of adiponectin in granulosa cell steroidogenesis. Reprod Camb Engl 2007;133:719–31.10.1530/REP-06-0244Suche in Google Scholar PubMed

126. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999;257:79–83.10.1006/bbrc.1999.0255Suche in Google Scholar PubMed

127. Wang ZV, Scherer PE. Adiponectin, cardiovascular function, and hypertension. Hypertension 2008;51:8–14.10.1161/HYPERTENSIONAHA.107.099424Suche in Google Scholar PubMed

128. Hoffstedt J, Arvidsson E, Sjölin E, Wåhlén K, Arner P. Adipose tissue adiponectin production and adiponectin serum concentration in human obesity and insulin resistance. J Clin Endocrinol Metab 2004;89:1391–6.10.1210/jc.2003-031458Suche in Google Scholar PubMed

129. Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000;20:1595–9.10.1161/01.ATV.20.6.1595Suche in Google Scholar PubMed

130. Neeland IJ, Ayers CR, Rohatgi AK, Turer AT, Berry JD, Das SR, Vega GL, Khera A, McGuire DK, Grundy SM, de Lemos JA. Associations of visceral and abdominal subcutaneous adipose tissue with markers of cardiac and metabolic risk in obese adults. Obes Silver Spring Md 2013;21:E439–47.10.1002/oby.20135Suche in Google Scholar PubMed PubMed Central

131. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001;7:941–6.10.1038/90984Suche in Google Scholar PubMed

132. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K. Adiponectin and adiponectin receptors in obesity-linked insulin resistance. Novartis Found Symp 2007;286:164–76; discussion 176–82, 200–3.10.1002/9780470985571.ch15Suche in Google Scholar PubMed

133. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001;86:1930–5.10.1210/jcem.86.5.7463Suche in Google Scholar

134. Antuna-Puente B, Feve B, Fellahi S, Bastard J-P. Adipokines: the missing link between insulin resistance and obesity. Diabetes Metab 2008;34:2–11.10.1016/j.diabet.2007.09.004Suche in Google Scholar

135. Okamoto Y. Adiponectin provides cardiovascular protection in metabolic syndrome. Cardiol Res Pract 2011;2011:313179.10.4061/2011/313179Suche in Google Scholar

136. Bai J, Liu Y, Niu G-F, Bai L-X, Xu X-Y, Zhang G-Z, Wang L-X. Relationship between adiponectin and testosterone in patients with type 2 diabetes. Biochem Medica Časopis Hrvat Druš Med Biokem HDMB 2011;21:65–70.10.11613/BM.2011.013Suche in Google Scholar

137. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 1995;270:26746–9.10.1074/jbc.270.45.26746Suche in Google Scholar

138. Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 1996;271:10697–703.10.1074/jbc.271.18.10697Suche in Google Scholar

139. Shapiro L, Scherer PE. The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Curr Biol 1998;8:335–8.10.1016/S0960-9822(98)70133-2Suche in Google Scholar

140. Wang Y, Lam KS, Yau M, Xu A. Post-translational modifications of adiponectin: mechanisms and functional implications. Biochem J 2008;409:623–33.10.1042/BJ20071492Suche in Google Scholar PubMed

141. Simpson F, Whitehead JP. Adiponectin – it’s all about the modifications. Int J Biochem Cell Biol 2010;42:785–8.10.1016/j.biocel.2009.12.021Suche in Google Scholar PubMed

142. Wang Y, Xu A, Knight C, Xu LY, Cooper GJ. Hydroxylation and glycosylation of the four conserved lysine residues in the collagenous domain of adiponectin. Potential role in the modulation of its insulin-sensitizing activity. J Biol Chem 2002;277:19521–9.10.1074/jbc.M200601200Suche in Google Scholar PubMed

143. Wang Y, Lam KS, Chan L, Chan KW, Lam JB, Lam MC, Hoo RCL, Mak WW, Cooper GJ, Xu A. Post-translational modifications of the four conserved lysine residues within the collagenous domain of adiponectin are required for the formation of its high molecular weight oligomeric complex. J Biol Chem 2006;281:16391–400.10.1074/jbc.M513907200Suche in Google Scholar PubMed

144. Richards AA, Stephens T, Charlton HK, Jones A, Macdonald GA, Prins JB, Whitehead JP. Adiponectin multimerization is dependent on conserved lysines in the collagenous domain: evidence for regulation of multimerization by alterations in posttranslational modifications. Mol Endocrinol 2006;20:1673–87.10.1210/me.2005-0390Suche in Google Scholar PubMed

145. Tsao T-S, Tomas E, Murrey HE, Hug C, Lee DH, Ruderman NB, Heuser JE, Lodish HF. Role of disulfide bonds in Acrp30/adiponectin structure and signaling specificity. Different oligomers activate different signal transduction pathways. J Biol Chem 2003;278:50810–7.10.1074/jbc.M309469200Suche in Google Scholar

146. Basu R, Pajvani UB, Rizza RA, Scherer PE. Selective downregulation of the high molecular weight form of adiponectin in hyperinsulinemia and in type 2 diabetes: differential regulation from nondiabetic subjects. Diabetes 2007;56:2174–7.10.2337/db07-0185Suche in Google Scholar PubMed

147. Pajvani UB, Hawkins M, Combs TP, Rajala MW, Doebber T, Berger JP, Wagner JA, Wu M, Knopps A, Xiang AH, Utzschneider KM, Kahn SE, Olefsky JM, Buchanan TA, Scherer PE. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem 2004;279:12152–62.10.1074/jbc.M311113200Suche in Google Scholar PubMed

148. Waki H, Yamauchi T, Kamon J, Ito Y, Uchida S, Kita S, Hara K, Hada Y, Vasseur F, Froguel P, Kimura S, Nagai R, Kadowaki T. Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. J Biol Chem 2003;278:40352–63.10.1074/jbc.M300365200Suche in Google Scholar PubMed

149. Ceddia RB, Somwar R, Maida A, Fang X, Bikopoulos G, Sweeney G. Globular adiponectin increases GLUT4 translocation and glucose uptake but reduces glycogen synthesis in rat skeletal muscle cells. Diabetologia 2005;48:132–9.10.1007/s00125-004-1609-ySuche in Google Scholar PubMed

150. Fang X, Palanivel R, Zhou X, Liu Y, Xu A, Wang Y, Sweeney G. Hyperglycemia- and hyperinsulinemia-induced alteration of adiponectin receptor expression and adiponectin effects in L6 myoblasts. J Mol Endocrinol 2005;35:465–76.10.1677/jme.1.01877Suche in Google Scholar PubMed

151. Tomas E, Tsao T-S, Saha AK, Murrey HE, Zhang CC, Itani SI, Lodish HF, Ruderman NB. Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc Natl Acad Sci USA 2002;99:16309–13.10.1073/pnas.222657499Suche in Google Scholar PubMed PubMed Central

152. Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT, Bihain BE, Lodish HF. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 2001;98:2005–10.10.1073/pnas.98.4.2005Suche in Google Scholar PubMed PubMed Central

153. Pajvani UB, Du X, Combs TP, Berg AH, Rajala MW, Schulthess T, Engel J, Brownlee M, Scherer PE. Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. Implications fpr metabolic regulation and bioactivity. J Biol Chem 2003;278:9073–85.10.1074/jbc.M207198200Suche in Google Scholar PubMed

154. Luque-Ramírez M, Martínez-García MÁ, Montes-Nieto R, Fernòndez-Duròn E, Insenser M, Alpañés M, Escobar-Morreale HF. Sexual dimorphism in adipose tissue function as evidenced by circulating adipokine concentrations in the fasting state and after an oral glucose challenge. Hum Reprod 2013;28:1908–18.10.1093/humrep/det097Suche in Google Scholar PubMed

155. Waki H, Yamauchi T, Kamon J, Kita S, Ito Y, Hada Y, Uchida S, Tsuchida A, Takekawa S, Kadowaki T. Generation of globular fragment of adiponectin by leukocyte elastase secreted by monocytic cell line THP-1. Endocrinology 2005;146:790–6.10.1210/en.2004-1096Suche in Google Scholar PubMed

156. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003;423:762–9.10.1038/nature01705Suche in Google Scholar PubMed

157. Yamauchi T, Nio Y, Maki T, Kobayashi M, Takazawa T, Iwabu M, Okada-Iwabu M, Kawamoto S, Kubota N, Kubota T, Ito Y, Kamon J, Tsuchida A, Kumagai K, Kozono H, Hada Y, Ogata H, Tokuyama K, Tsunoda M, Ide T, Murakami K, Awazawa M, Takamoto I, Froguel P, Hara K, Tobe K, Nagai R, Ueki K, Kadowaki T. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med 2007;13:332–9.10.1038/nm1557Suche in Google Scholar PubMed

158. Bjursell M, Ahnmark A, Bohlooly-YM, William-Olsson L, Rhedin M, Peng X-R, Ploj K, Gerdin A-K, Arnerup G, Elmgren A, Berg A-L, Oscarsson J, Lindén D. Opposing effects of adiponectin receptors 1 and 2 on energy metabolism. Diabetes 2007;56:583–93.10.2337/db06-1432Suche in Google Scholar PubMed

159. Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N, Kondo H, Takahashi M, Arita Y, Komuro R, Ouchi N, Kihara S, Tochino Y, Okutomi K, Horie M, Takeda S, Aoyama T, Funahashi T, Matsuzawa Y. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 2002;8:731–7.10.1038/nm724Suche in Google Scholar PubMed

160. Otani M, Kogo M, Furukawa S, Wakisaka S, Maeda T. The adiponectin paralog C1q/TNF-related protein 3 (CTRP3) stimulates testosterone production through the cAMP/PKA signaling pathway. Cytokine 2012;58:238–44.10.1016/j.cyto.2012.01.018Suche in Google Scholar PubMed

161. Martin LJ. Implications of adiponectin in linking metabolism to testicular function. Endocrine 2013;46:16–28.10.1007/s12020-013-0102-0Suche in Google Scholar PubMed

162. Civitarese AE, Jenkinson CP, Richardson D, Bajaj M, Cusi K, Kashyap S, Berria R, Belfort R, DeFronzo RA, Mandarino LJ, Ravussin E. Adiponectin receptors gene expression and insulin sensitivity in non-diabetic Mexican Americans with or without a family history of Type 2 diabetes. Diabetologia 2004;47:816–20.10.1007/s00125-004-1359-xSuche in Google Scholar PubMed

163. Lord E, Ledoux S, Murphy BD, Beaudry D, Palin MF. Expression of adiponectin and its receptors in swine. J Anim Sci 2005;83:565–78.10.2527/2005.833565xSuche in Google Scholar PubMed

164. Ledoux S, Campos DB, Lopes FL, Dobias-Goff M, Palin M-F, Murphy BD. Adiponectin induces periovulatory changes in ovarian follicular cells. Endocrinology 2006;147:5178–86.10.1210/en.2006-0679Suche in Google Scholar PubMed

165. Ramachandran R, Ocón-Grove OM, Metzger SL. Molecular cloning and tissue expression of chicken AdipoR1 and AdipoR2 complementary deoxyribonucleic acids. Domest Anim Endocrinol 2007;33:19–31.10.1016/j.domaniend.2006.04.004Suche in Google Scholar PubMed

166. Chabrolle C, Tosca L, Crochet S, Tesseraud S, Dupont J. Expression of adiponectin and its receptors (AdipoR1 and AdipoR2) in chicken ovary: potential role in ovarian steroidogenesis. Domest Anim Endocrinol 2007;33:480–7.10.1016/j.domaniend.2006.08.002Suche in Google Scholar PubMed

167. Pfaehler A, Nanjappa MK, Coleman ES, Mansour M, Wanders D, Plaisance EP, Judd RL, Akingbemi BT. Regulation of adiponectin secretion by soy isoflavones has implication for endocrine function of the testis. Toxicol Lett 2012;209:78–85.10.1016/j.toxlet.2011.11.027Suche in Google Scholar PubMed

168. Combs TP, Berg AH, Rajala MW, Klebanov S, Iyengar P, Jimenez-Chillaron JC, Patti ME, Klein SL, Weinstein RS, Scherer PE. Sexual differentiation, pregnancy, calorie restriction, and aging affect the adipocyte-specific secretory protein adiponectin. Diabetes 2003;52:268–76.10.2337/diabetes.52.2.268Suche in Google Scholar PubMed

169. Hug C, Wang J, Ahmad NS, Bogan JS, Tsao T-S, Lodish HF. T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. Proc Natl Acad Sci USA 2004;101:10308–13.10.1073/pnas.0403382101Suche in Google Scholar PubMed PubMed Central

170. Asada K, Yoshiji H, Noguchi R, Ikenaka Y, Kitade M, Kaji K, Yoshii J, Yanase K, Namisaki T, Yamazaki M, Tsujimoto T, Akahane T, Uemura M, Fukui H. Crosstalk between high-molecular-weight adiponectin and T-cadherin during liver fibrosis development in rats. Int J Mol Med 2007;20:725–9.Suche in Google Scholar

171. Denzel MS, Scimia M-C, Zumstein PM, Walsh K, Ruiz-Lozano P, Ranscht B. T-cadherin is critical for adiponectin-mediated cardioprotection in mice. J Clin Invest 2010;120:4342–52.10.1172/JCI43464Suche in Google Scholar PubMed PubMed Central

172. Takeuchi T, Adachi Y, Ohtsuki Y, Furihata M. Adiponectin receptors, with special focus on the role of the third receptor, T-cadherin, in vascular disease. Med Mol Morphol 2007;40:115–20.10.1007/s00795-007-0364-9Suche in Google Scholar PubMed

173. Andreeva AV, Han J, Kutuzov MA, Profirovic J, Tkachuk VA, Voyno-Yasenetskaya TA. T-cadherin modulates endothelial barrier function. J Cell Physiol 2010;223:94–102.10.1002/jcp.22014Suche in Google Scholar

174. Munro SB, Blaschuk OW. A comprehensive survey of the cadherins expressed in the testes of fetal, immature, and adult mice utilizing the polymerase chain reaction. Biol Reprod 1996;55:822–7.10.1095/biolreprod55.4.822Suche in Google Scholar PubMed

175. Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev 2005;26:439–51.10.1210/er.2005-0005Suche in Google Scholar PubMed

176. Caminos JE, Nogueiras R, Gallego R, Bravo S, Tovar S, García-Caballero T, Casanueva FF, Diéguez C. Expression and regulation of adiponectin and receptor in human and rat placenta. J Clin Endocrinol Metab 2005;90:4276–86.10.1210/jc.2004-0930Suche in Google Scholar PubMed

177. Li P, Sun F, Cao H-M, Ma Q-Y, Pan C-M, Ma J-H, Zhang X-N, Jiang H, Song H-D, Chen M-D. Expression of adiponectin receptors in mouse adrenal glands and the adrenocortical Y-1 cell line: Adiponectin regulates steroidogenesis. Biochem Biophys Res Commun 2009;390:1208–13.10.1016/j.bbrc.2009.10.122Suche in Google Scholar PubMed

178. Li Y, Ramdhan DH, Naito H, Yamagishi N, Ito Y, Hayashi Y, Yanagiba Y, Okamura A, Tamada H, Gonzalez FJ, Nakajima T. Ammonium perfluorooctanoate may cause testosterone reduction by adversely affecting testis in relation to PPARα. Toxicol Lett 2011;205:265–72.10.1016/j.toxlet.2011.06.015Suche in Google Scholar PubMed PubMed Central

179. Brion L, Maloberti PM, Gomez NV, Poderoso C, Gorostizaga AB, Mori Sequeiros Garcia MM, Acquier AB, Cooke M, Mendez CF, Podesta EJ, Paz C. MAPK phosphatase-1 (MKP-1) expression is up-regulated by hCG/cAMP and modulates steroidogenesis in MA-10 Leydig cells. Endocrinology 2011;152:2665–77.10.1210/en.2011-0021Suche in Google Scholar PubMed

180. Ahn SW, Gang G-T, Tadi S, Nedumaran B, Kim YD, Park JH, Kweon GR, Koo S-H, Lee K, Ahn R-S, Yim Y-H, Lee C-H, Harris RA, Choi H-S. Phosphoenolpyruvate carboxykinase and glucose-6-phosphatase are required for steroidogenesis in testicular Leydig cells. J Biol Chem 2012;287:41875–87.10.1074/jbc.M112.421552Suche in Google Scholar PubMed PubMed Central

181. Lagaly DV, Aad PY, Grado-Ahuir JA, Hulsey LB, Spicer LJ. Role of adiponectin in regulating ovarian theca and granulosa cell function. Mol Cell Endocrinol 2008;284:38–45.10.1016/j.mce.2008.01.007Suche in Google Scholar PubMed

182. Chabrolle C, Tosca L, Ramé C, Lecomte P, Royère D, Dupont J. Adiponectin increases insulin-like growth factor I-induced progesterone and estradiol secretion in human granulosa cells. Fertil Steril 2009;92:1988–96.10.1016/j.fertnstert.2008.09.008Suche in Google Scholar PubMed

183. Richards JS, Liu Z, Kawai T, Tabata K, Watanabe H, Suresh D, Kuo F-T, Pisarska MD, Shimada M. Adiponectin and its receptors modulate granulosa cell and cumulus cell functions, fertility, and early embryo development in the mouse and human. Fertil Steril 2012;98:471–9.e1.10.1016/j.fertnstert.2012.04.050Suche in Google Scholar PubMed PubMed Central

184. Ramanjaneya M, Conner AC, Brown JE, Chen J, Digby JE, Barber TM, Lehnert H, Randeva HS. Adiponectin (15-36) stimulates steroidogenic acute regulatory (StAR) protein expression and cortisol production in human adrenocortical cells: role of AMPK and MAPK kinase pathways. Biochim Biophys Acta 2011;1813:802–9.10.1016/j.bbamcr.2011.02.010Suche in Google Scholar PubMed

185. Landry D, Paré A, Jean S, Martin LJ. Adiponectin influences progesterone production from MA-10 Leydig cells in a dose-dependent manner. Endocrine 2015;48:957–67.10.1007/s12020-014-0456-ySuche in Google Scholar PubMed

186. Tosca L, Froment P, Solnais P, Ferré P, Foufelle F, Dupont J. Adenosine 5′-monophosphate-activated protein kinase regulates progesterone secretion in rat granulosa cells. Endocrinology 2005;146:4500–13.10.1210/en.2005-0301Suche in Google Scholar

187. Tosca L, Chabrolle C, Uzbekova S, Dupont J. Effects of metformin on bovine granulosa cells steroidogenesis: possible involvement of adenosine 5′ monophosphate-activated protein kinase (AMPK). Biol Reprod 2007;76:368–78.10.1095/biolreprod.106.055749Suche in Google Scholar

188. Martin LJ. Implications of adiponectin in linking metabolism to testicular function. Endocrine 2014;46:16–28.10.1007/s12020-013-0102-0Suche in Google Scholar

189. Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, Spiegelman BM, Mortensen RM. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell 1999;4:611–7.10.1016/S1097-2765(00)80211-7Suche in Google Scholar

190. Schultz R, Yan W, Toppari J, Völkl A, Gustafsson JA, Pelto-Huikko M. Expression of peroxisome proliferator-activated receptor alpha messenger ribonucleic acid and protein in human and rat testis. Endocrinology 1999;140:2968–75.10.1210/endo.140.7.6858Suche in Google Scholar PubMed

191. Lin H, Yu C-H, Jen C-Y, Cheng C-F, Chou Y, Chang C-C, Juan S-H. Adiponectin-mediated heme oxygenase-1 induction protects against iron-induced liver injury via a PPARα dependent mechanism. Am J Pathol 2010;177:1697–709.10.2353/ajpath.2010.090789Suche in Google Scholar PubMed PubMed Central

192. Liu L-F, Shen W-J, Zhang ZH, Wang LJ, Kraemer FB. Adipocytes decrease Runx2 expression in osteoblastic cells: roles of PPARγ and adiponectin. J Cell Physiol 2010;225:837–45.10.1002/jcp.22291Suche in Google Scholar PubMed

193. Lee F-P, Jen C-Y, Chang C-C, Chou Y, Lin H, Chou C-M, Juan S-H. Mechanisms of adiponectin-mediated COX-2 induction and protection against iron injury in mouse hepatocytes. J Cell Physiol 2010;224:837–47.10.1002/jcp.22192Suche in Google Scholar PubMed

194. Peters JM, Lee SS, Li W, Ward JM, Gavrilova O, Everett C, Reitman ML, Hudson LD, Gonzalez FJ. Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta). Mol Cell Biol 2000;20:5119–28.10.1128/MCB.20.14.5119-5128.2000Suche in Google Scholar PubMed PubMed Central

195. Lee SS, Pineau T, Drago J, Lee EJ, Owens JW, Kroetz DL, Fernandez-Salguero PM, Westphal H, Gonzalez FJ. Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol Cell Biol 1995;15:3012–22.10.1128/MCB.15.6.3012Suche in Google Scholar PubMed PubMed Central

196. Repa JJ, Mangelsdorf DJ. The role of orphan nuclear receptors in the regulation of cholesterol homeostasis. Annu Rev Cell Dev Biol 2000;16:459–81.10.1146/annurev.cellbio.16.1.459Suche in Google Scholar

197. Volle DH, Lobaccaro J-M. Role of the nuclear receptors for oxysterols LXRs in steroidogenic tissues: beyond the “foie gras”, the steroids and sex? Mol Cell Endocrinol 2007;265–266:183–9.10.1016/j.mce.2006.12.018Suche in Google Scholar

198. Volle DH, Mouzat K, Duggavathi R, Siddeek B, Déchelotte P, Sion B, Veyssière G, Benahmed M, Lobaccaro J-M. Multiple roles of the nuclear receptors for oxysterols liver X receptor to maintain male fertility. Mol Endocrinol 2007;21:1014–27.10.1210/me.2006-0277Suche in Google Scholar

199. Robertson KM, Schuster GU, Steffensen KR, Hovatta O, Meaney S, Hultenby K, Johansson LC, Svechnikov K, Söder O, Gustafsson J-A. The liver X receptor-{beta} is essential for maintaining cholesterol homeostasis in the testis. Endocrinology 2005;146:2519–30.10.1210/en.2004-1413Suche in Google Scholar

200. Lee JH, Gong H, Khadem S, Lu Y, Gao X, Li S, Zhang J, Xie W. Androgen deprivation by activating the liver X receptor. Endocrinology 2008;149:3778–88.10.1210/en.2007-1605Suche in Google Scholar

201. Maqdasy S, Baptissart M, Vega A, Baron S, Lobaccaro J-M, Volle DH. Cholesterol and male fertility: what about orphans and adopted? Mol Cell Endocrinol 2013;368:30–46.10.1016/j.mce.2012.06.011Suche in Google Scholar

202. Ozbay T, Rowan A, Leon A, Patel P, Sewer MB. Cyclic adenosine 5′-monophosphate-dependent sphingosine-1-phosphate biosynthesis induces human CYP17 gene transcription by activating cleavage of sterol regulatory element binding protein 1. Endocrinology 2006;147:1427–37.10.1210/en.2005-1091Suche in Google Scholar

203. Wang H, Chen J, Hollister K, Sowers LC, Forman BM. Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol Cell 1999;3:543–53.10.1016/S1097-2765(00)80348-2Suche in Google Scholar

204. Catalano S, Malivindi R, Giordano C, Gu G, Panza S, Bonofiglio D, Lanzino M, Sisci D, Panno ML, Andò S. Farnesoid X receptor, through the binding with steroidogenic factor 1-responsive element, inhibits aromatase expression in tumor Leydig cells. J Biol Chem 2010;285:5581–93.10.1074/jbc.M109.052670Suche in Google Scholar PubMed PubMed Central

205. Volle DH, Duggavathi R, Magnier BC, Houten SM, Cummins CL, Lobaccaro J-M, Verhoeven G, Schoonjans K, Auwerx J. The small heterodimer partner is a gonadal gatekeeper of sexual maturation in male mice. Genes Dev 2007;21:303–15.10.1101/gad.409307Suche in Google Scholar PubMed PubMed Central

206. Cipriani S, Mencarelli A, Palladino G, Fiorucci S. FXR activation reverses insulin resistance and lipid abnormalities and protects against liver steatosis in Zucker (fa/fa) obese rats. J Lipid Res 2010;51:771–84.10.1194/jlr.M001602Suche in Google Scholar

207. Yan K, Deng X, Zhai X, Zhou M, Jia X, Luo L, Niu M, Zhu H, Qiang H, Zhou Y. p38 mitogen-activated protein kinase and liver X receptor-α mediate the leptin effect on sterol regulatory element binding protein-1c expression in hepatic stellate cells. Mol Med 2012;18:10–8.10.2119/molmed.2011.00243Suche in Google Scholar

208. Boulogne B, Levacher C, Durand P, Habert R. Retinoic acid receptors and retinoid X receptors in the rat testis during fetal and postnatal development: immunolocalization and implication in the control of the number of gonocytes. Biol Reprod 1999;61:1548–57.10.1095/biolreprod61.6.1548Suche in Google Scholar

209. Chaudhary LR, Hutson JC, Stocco DM. Effect of retinol and retinoic acid on testosterone production by rat Leydig cells in primary culture. Biochem Biophys Res Commun 1989;158:400–6.10.1016/S0006-291X(89)80061-0Suche in Google Scholar

210. Lefèvre A, Rogier E, Astraudo C, Duquenne C, Finaz C. Regulation by retinoids of luteinizing hormone/chorionic gonadotropin receptor, cholesterol side-chain cleavage cytochrome P-450, 3 beta-hydroxysteroid dehydrogenase/delta (5-4)-isomerase and 17 alpha-hydroxylase/C17-20 lyase cytochrome P-450 messenger ribonucleic acid levels in the K9 mouse Leydig cell line. Mol Cell Endocrinol 1994;106:31–9.10.1016/0303-7207(94)90183-XSuche in Google Scholar

211. Appling DR, Chytil F. Evidence of a role for retinoic acid (vitamin A-acid) in the maintenance of testosterone production in male rats. Endocrinology 1981;108:2120–4.10.1210/endo-108-6-2120Suche in Google Scholar PubMed

212. Tucci P, Cione E, Perri M, Genchi G. All-trans-retinoic acid induces apoptosis in Leydig cells via activation of the mitochondrial death pathway and antioxidant enzyme regulation. J Bioenerg Biomembr 2008;40:315–23.10.1007/s10863-008-9156-8Suche in Google Scholar PubMed

213. King SR, LaVoie HA. Gonadal transactivation of STARD1, CYP11A1 and HSD3B. Front Biosci 2012;17:824–46.10.2741/3959Suche in Google Scholar PubMed

214. Park P, Huang H, McMullen MR, Bryan K, Nagy LE. Activation of cyclic-AMP response element binding protein contributes to adiponectin-stimulated interleukin-10 expression in RAW 264.7 macrophages. J Leukoc Biol 2008;83:1258–66.10.1189/jlb.0907631Suche in Google Scholar PubMed

215. Shih M-C, Chiu Y-N, Hu M-C, Guo I-C, Chung B. Regulation of steroid production: analysis of Cyp11a1 promoter. Mol Cell Endocrinol 2011;336:80–4.10.1016/j.mce.2010.12.017Suche in Google Scholar PubMed

216. Pena P, Reutens AT, Albanese C, D’Amico M, Watanabe G, Donner A, Shu IW, Williams T, Pestell RG. Activator protein-2 mediates transcriptional activation of the CYP11A1 gene by interaction with Sp1 rather than binding to DNA. Mol Endocrinol 1999;13:1402–16.10.1210/mend.13.8.0335Suche in Google Scholar PubMed

217. Sugawara T, Saito M, Fujimoto S. Sp1 and SF-1 interact and cooperate in the regulation of human steroidogenic acute regulatory protein gene expression. Endocrinology 2000;141:2895–903.10.1210/endo.141.8.7602Suche in Google Scholar PubMed

218. Momoi K, Waterman MR, Simpson ER, Zanger UM. 3′,5′-cyclic adenosine monophosphate-dependent transcription of the CYP11A (cholesterol side chain cleavage cytochrome P450) gene involves a DNA response element containing a putative binding site for transcription factor Sp1. Mol Endocrinol 1992;6:1682–90.10.1210/mend.6.10.1333053Suche in Google Scholar

219. Wen J-P, Liu C, Bi W-K, Hu Y-T, Chen Q, Huang H, Liang J-X, Li L-T, Lin L-X, Chen G. Adiponectin inhibits KISS1 gene transcription through AMPK and specificity protein-1 in the hypothalamic GT1-7 neurons. J Endocrinol 2012;214:177–89.10.1530/JOE-12-0054Suche in Google Scholar PubMed

220. Milanini-Mongiat J, Pouysségur J, Pagès G. Identification of two Sp1 phosphorylation sites for p42/p44 mitogen-activated protein kinases: their implication in vascular endothelial growth factor gene transcription. J Biol Chem 2002;277:20631–9.10.1074/jbc.M201753200Suche in Google Scholar PubMed

221. El-Asmar B, Giner XC, Tremblay JJ. Transcriptional cooperation between NF-kappaB p50 and CCAAT/enhancer binding protein beta regulates Nur77 transcription in Leydig cells. J Mol Endocrinol 2009;42:131–8.10.1677/JME-08-0016Suche in Google Scholar PubMed

222. Hong CY, Park JH, Ahn RS, Im SY, Choi H-S, Soh J, Mellon SH, Lee K. Molecular mechanism of suppression of testicular steroidogenesis by proinflammatory cytokine tumor necrosis factor alpha. Mol Cell Biol 2004;24:2593–604.10.1128/MCB.24.7.2593-2604.2004Suche in Google Scholar PubMed PubMed Central

223. Fayard E, Auwerx J, Schoonjans K. LRH-1: an orphan nuclear receptor involved in development, metabolism and steroidogenesis. Trends Cell Biol 2004;14:250–60.10.1016/j.tcb.2004.03.008Suche in Google Scholar PubMed

224. Pezzi V, Sirianni R, Chimento A, Maggiolini M, Bourguiba S, Delalande C, Carreau S, Andò S, Simpson ER, Clyne CD. Differential expression of steroidogenic factor-1/adrenal 4 binding protein and liver receptor homolog-1 (LRH-1)/fetoprotein transcription factor in the rat testis: LRH-1 as a potential regulator of testicular aromatase expression. Endocrinology 2004;145:2186–96.10.1210/en.2003-1366Suche in Google Scholar PubMed

225. Mueller M, Cima I, Noti M, Fuhrer A, Jakob S, Dubuquoy L, Schoonjans K, Brunner T. The nuclear receptor LRH-1 critically regulates extra-adrenal glucocorticoid synthesis in the intestine. J Exp Med 2006;203:2057–62.10.1084/jem.20060357Suche in Google Scholar PubMed PubMed Central

226. Sirianni R, Seely JB, Attia G, Stocco DM, Carr BR, Pezzi V, Rainey WE. Liver receptor homologue-1 is expressed in human steroidogenic tissues and activates transcription of genes encoding steroidogenic enzymes. J Endocrinol 2002;174:R13–7.10.1677/joe.0.174r013Suche in Google Scholar PubMed

227. Wang ZN, Bassett M, Rainey WE. Liver receptor homologue-1 is expressed in the adrenal and can regulate transcription of 11 beta-hydroxylase. J Mol Endocrinol 2001;27:255–8.10.1677/jme.0.0270255Suche in Google Scholar PubMed

228. Sierens J, Jakody I, Poobalan Y, Meachem SJ, Knower K, Young MJ, Sirianni R, Pezzi V, Clyne CD. Localization and regulation of aromatase liver receptor homologue-1 in the developing rat testis. Mol Cell Endocrinol 2010;323:307–13.10.1016/j.mce.2010.03.001Suche in Google Scholar PubMed

229. Iwaki M, Matsuda M, Maeda N, Funahashi T, Matsuzawa Y, Makishima M, Shimomura I. Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors. Diabetes 2003;52:1655–63.10.2337/diabetes.52.7.1655Suche in Google Scholar PubMed

230. McCabe ER. DAX1: Increasing complexity in the roles of this novel nuclear receptor. Mol Cell Endocrinol 2007; 265–266:179–82.10.1016/j.mce.2006.12.017Suche in Google Scholar PubMed PubMed Central

231. Yu RN, Ito M, Saunders TL, Camper SA, Jameson JL. Role of Ahch in gonadal development and gametogenesis. Nat Genet 1998;20:353–7.10.1038/3822Suche in Google Scholar PubMed

232. Jo Y, Stocco DM. Regulation of steroidogenesis and steroidogenic acute regulatory protein in R2C cells by DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia congenita, critical region on the X chromosome, gene-1). Endocrinology 2004;145:5629–37.10.1210/en.2004-0941Suche in Google Scholar PubMed

233. Wang ZJ, Jeffs B, Ito M, Achermann JC, Yu RN, Hales DB, Jameson JL. Aromatase (Cyp19) expression is up-regulated by targeted disruption of Dax1. Proc Natl Acad Sci USA 2001;98:7988–93.10.1073/pnas.141543298Suche in Google Scholar PubMed PubMed Central

234. Suzuki T, Kasahara M, Yoshioka H, Morohashi K-I, Umesono K. LXXLL-related motifs in Dax-1 have target specificity for the orphan nuclear receptors Ad4BP/SF-1 and LRH-1. Mol Cell Biol 2003;23:238–49.10.1128/MCB.23.1.238-249.2003Suche in Google Scholar PubMed PubMed Central

235. Silha JV, Krsek M, Skrha JV, Sucharda P, Nyomba BL, Murphy LJ. Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur J Endocrinol 2003;149:331–5.10.1530/eje.0.1490331Suche in Google Scholar PubMed

236. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA. The hormone resistin links obesity to diabetes. Nature 2001;409:307–12.10.1038/35053000Suche in Google Scholar PubMed

237. Daquinag AC, Zhang Y, Amaya-Manzanares F, Simmons PJ, Kolonin MG. An isoform of decorin is a resistin receptor on the surface of adipose progenitor cells. Cell Stem Cell 2011;9:74–86.10.1016/j.stem.2011.05.017Suche in Google Scholar PubMed

238. Benomar Y, Gertler A, De Lacy P, Crépin D, Ould Hamouda H, Riffault L, Taouis M. Central resistin overexposure induces insulin resistance through Toll-like receptor 4. Diabetes 2013;62:102–14.10.2337/db12-0237Suche in Google Scholar PubMed PubMed Central

239. Sònchez-Solana B, Laborda J, Baladrón V. Mouse resistin modulates adipogenesis and glucose uptake in 3T3-L1 preadipocytes through the ROR1 receptor. Mol Endocrinol 2012;26:110–27.10.1210/me.2011-1027Suche in Google Scholar PubMed PubMed Central

240. Kim HJ, Lee YS, Won EH, Chang IH, Kim TH, Park ES, Kim MK, Kim W, Myung SC. Expression of resistin in the prostate and its stimulatory effect on prostate cancer cell proliferation. BJU Int 2011;108:E77–83.10.1111/j.1464-410X.2010.09813.xSuche in Google Scholar PubMed

241. Ou H-C, Lee W-J, Wu C-M, Chen JF, Sheu WH. Aspirin prevents resistin-induced endothelial dysfunction by modulating AMPK, ROS, and Akt/eNOS signaling. J Vasc Surg 2012;55:1104–15.10.1016/j.jvs.2011.10.011Suche in Google Scholar PubMed

242. Arakane F, King SR, Du Y, Kallen CB, Walsh LP, Watari H, Stocco DM, Strauss JF 3rd. Phosphorylation of steroidogenic acute regulatory protein (StAR) modulates its steroidogenic activity. J Biol Chem 1997;272:32656–62.10.1074/jbc.272.51.32656Suche in Google Scholar PubMed

243. Spicer LJ, Schreiber NB, Lagaly DV, Aad PY, Douthit LB, Grado-Ahuir JA. Effect of resistin on granulosa and theca cell function in cattle. Anim Reprod Sci 2011;124:19–27.10.1016/j.anireprosci.2011.01.005Suche in Google Scholar PubMed

244. Nogueiras R, Gualillo O, Caminos JE, Casanueva FF, Diéguez C. Regulation of resistin by gonadal, thyroid hormone, and nutritional status. Obes Res 2003;11:408–14.10.1038/oby.2003.55Suche in Google Scholar PubMed

245. Morash BA, Ur E, Wiesner G, Roy J, Wilkinson M. Pituitary resistin gene expression: effects of age, gender and obesity. Neuroendocrinology 2004;79:149–56.10.1159/000077273Suche in Google Scholar PubMed

246. Huang S-W, Seow K-M, Ho L-T, Chien Y, Chung D-Y, Chang C-L, Lai Y-H, Hwang J-L, Juan C-C. Resistin mRNA levels are downregulated by estrogen in vivo and in vitro. FEBS Lett 2005;579:449–54.10.1016/j.febslet.2004.12.010Suche in Google Scholar PubMed

247. Pravenec M, Kazdovò L, Landa V, Zidek V, Mlejnek P, Jansa P, Wang J, Qi N, Kurtz TW. Transgenic and recombinant resistin impair skeletal muscle glucose metabolism in the spontaneously hypertensive rat. J Biol Chem 2003;278:45209–15.10.1074/jbc.M304869200Suche in Google Scholar PubMed

248. Rangwala SM, Rich AS, Rhoades B, Shapiro JS, Obici S, Rossetti L, Lazar MA. Abnormal glucose homeostasis due to chronic hyperresistinemia. Diabetes 2004;53:1937–41.10.2337/diabetes.53.8.1937Suche in Google Scholar PubMed

249. Pirvulescu M, Manduteanu I, Gan AM, Stan D, Simion V, Butoi E, Calin M, Simionescu M. A novel pro-inflammatory mechanism of action of resistin in human endothelial cells: Up-regulation of SOCS3 expression through STAT3 activation. Biochem Biophys Res Commun 2012;422:321–6.10.1016/j.bbrc.2012.04.159Suche in Google Scholar PubMed

250. Tarkowski A, Bjersing J, Shestakov A, Bokarewa MI. Resistin competes with lipopolysaccharide for binding to toll-like receptor 4. J Cell Mol Med 2010;14:1419–31.10.1111/j.1582-4934.2009.00899.xSuche in Google Scholar PubMed PubMed Central

251. Shang T, Zhang X, Wang T, Sun B, Deng T, Han D. Toll-like receptor-initiated testicular innate immune responses in mouse Leydig cells. Endocrinology 2011;152:2827–36.10.1210/en.2011-0031Suche in Google Scholar PubMed

252. Stephanou A, Latchman DS. Opposing actions of STAT-1 and STAT-3. Growth Factors 2005;23:177–82.10.1080/08977190500178745Suche in Google Scholar PubMed

253. Rak-Mardy AA, Drwal E. In vitro interaction between resistin and peroxisome proliferator-activated receptor γ in porcine ovarian follicles. Reprod Fertil Dev 2014. http://dx.doi.org/10.1071/RD14053.10.1071/RD14053Suche in Google Scholar PubMed

254. Bokarewa M, Nagaev I, Dahlberg L, Smith U, Tarkowski A. Resistin, an adipokine with potent proinflammatory properties. J Immunol 2005;174:5789–95.10.4049/jimmunol.174.9.5789Suche in Google Scholar PubMed

255. Bertolani C, Sancho-Bru P, Failli P, Bataller R, Aleffi S, DeFranco R, Mazzinghi B, Romagnani P, Milani S, Ginés P, Colmenero J, Parola M, Gelmini S, Tarquini R, Laffi G, Pinzani M, Marra F. Resistin as an intrahepatic cytokine: overexpression during chronic injury and induction of proinflammatory actions in hepatic stellate cells. Am J Pathol 2006;169:2042–53.10.2353/ajpath.2006.060081Suche in Google Scholar PubMed PubMed Central

256. Wang Q, Gao H-B. Involvement of nuclear factor-kappa B on corticosterone- induced rat Leydig cell apoptosis. Asian J Androl 2006;8:693–702.10.1111/j.1745-7262.2006.00212.xSuche in Google Scholar PubMed

257. Pao H-Y, Pan B-S, Leu S-F, Huang B-M. Cordycepin stimulated steroidogenesis in MA-10 mouse Leydig tumor cells through the protein kinase C Pathway. J Agric Food Chem 2012;60:4905–13.10.1021/jf205091bSuche in Google Scholar

258. Manna PR, Stocco DM. The role of specific mitogen-activated protein kinase signaling cascades in the regulation of steroidogenesis. J Signal Transduct 2011;2011:821615.10.1155/2011/821615Suche in Google Scholar

259. Pitteloud N, Mootha VK, Dwyer AA, Hardin M, Lee H, Eriksson K-F, Tripathy D, Yialamas M, Groop L, Elahi D, Hayes FJ. Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men. Diabetes Care 2005;28:1636–42.10.2337/diacare.28.7.1636Suche in Google Scholar

260. Bebakar WM, Honour JW, Foster D, Liu YL, Jacobs HS. Regulation of testicular function by insulin and transforming growth factor-beta. Steroids 1990;55:266–70.10.1016/0039-128X(90)90043-BSuche in Google Scholar

261. Ahn SW, Gang G-T, Kim YD, Ahn R-S, Harris RA, Lee C-H, Choi H-S. Insulin directly regulates steroidogenesis via induction of the orphan nuclear receptor DAX-1 in testicular Leydig cells. J Biol Chem 2013;288:15937–46.10.1074/jbc.M113.451773Suche in Google Scholar

262. Båvner A, Sanyal S, Gustafsson J-A, Treuter E. Transcriptional corepression by SHP: molecular mechanisms and physiological consequences. Trends Endocrinol Metab 2005;16:478–88.10.1016/j.tem.2005.10.005Suche in Google Scholar

263. Brendel C, Schoonjans K, Botrugno OA, Treuter E, Auwerx J. The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity. Mol Endocrinol 2002;16:2065–76.10.1210/me.2001-0194Suche in Google Scholar

264. Bakke M, Zhao L, Hanley NA, Parker KL. SF-1: a critical mediator of steroidogenesis. Mol Cell Endocrinol 2001;171:5–7.10.1016/S0303-7207(00)00384-1Suche in Google Scholar

265. Bray GA. Medical consequences of obesity. J Clin Endocrinol Metab 2004;89:2583–9.10.1210/jc.2004-0535Suche in Google Scholar PubMed