Skip to main content
SpringerLink
Log in

Regulation of Leydig Cell Function as it Pertains to the Inflammatory Response

  • Chapter
The Leydig Cell in Health and Disease

Part of the book series: Contemporary Endocrinology ((COE))

Abstract

The immune-endocrine interactions that govern Leydig cell function are described in relation to both positive, trophic interactions of immune regulatory effects during development and in the normal, healthy noninflamed testis, and inhibitory effects of the same mediators in response to inflammation, infection, and chronic illness. The unique immune environment of the testes is detailed with particular emphasis on the functional significance of the close physical association between testicular interstitial macrophages and Leydig cells. The role of four classes of inflammatory mediators in the regulation of Leydig cell functions is discussed in detail: proinflammatory cytokines, reactive oxygen species, nitric oxide, and prostaglandins. The role of immune-dysregulation in the decline of steroidogenic function is addressed in the context of how macrophage-Leydig cell interactions change in the aging male.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Hales DB. Leydig cell-macrophage interactions: an overview. In: Payne AH, Hardy MP, Russell LD, eds. The Leydig Cell. Vienna, IL: Cache River Press, 1996;1:451–466.

    Google Scholar 

  2. Hales DB. Testicular macrophage modulation of Leydig cell steroidogenesis. J Reprod Immunol 2002;57(1-2):3–18.

    PubMed  CAS  Google Scholar 

  3. Hales DB, Diemer T, Hales KH. Role of cytokines in testicular function. Endocrine 1999;10(3):201–217.

    PubMed  CAS  Google Scholar 

  4. Perez-Clavier R, Harrison RG, Macmillian EW. The pattern of the lymphatic drainage of the rat epididymis. J Anat 1982;134(part4):667–675.

    PubMed  CAS  Google Scholar 

  5. Fawcett DW, Heidger PM, Leak LV. Lymph vascular system of the interstitial tissue of the testis as revealed by electron microscopy. J Reprod Fertil 1969;19(1):109–119.

    PubMed  CAS  Google Scholar 

  6. Waites GM, Gladwell RT. Physiological significance of fluid secretion in the testis and blood-testis barrier. Physiol Rev 1982;62(2):624–671.

    PubMed  CAS  Google Scholar 

  7. Setchell BP. The blood-testicular fluid barrier in sheep. J Physiol 1967;189(2):63P–65P.

    PubMed  CAS  Google Scholar 

  8. Selawry HP, Whittington KB. Prolonged intratesticular islet allograft survival is not dependent on local steroidogenesis. Horm Metab Res 1988;20(9):562–565.

    PubMed  CAS  Google Scholar 

  9. Selawry HP, Whittington K. Extended allograft survival of islets grafted into intra-abdominally placed testis. Diabetes 1984;33(4):405–406.

    PubMed  CAS  Google Scholar 

  10. Baker HW. Reproductive effects of nontesticular illness. Endocrinol Metab Clin North Am 1998;27(4):831–850.

    PubMed  CAS  Google Scholar 

  11. Dong Q, Hawker F, McWilliam D, Bangah M, Burger H, Handelsman DJ. Circulating immunoreactive inhibin and testosterone levels in men with critical illness. Clin Endocrinol 1992;36(4):399–404.

    CAS  Google Scholar 

  12. Anton F, Morales C, Aguilar R, Bellido C, Aguilar E, Gaytan F. A comparative study of mast cells and eosinophil leukocytes in the mammalian testis. Zentralbl Veterinarmed [A] 1998; 45(4):209–218.

    CAS  Google Scholar 

  13. Hutson JC. Testicular macrophages. Int Rev Cytol 1994;149: 99–143.

    PubMed  CAS  Google Scholar 

  14. Dym M, Romrell LJ. Intraepithelial lymphocytes in the male reproductive tract of rats and rhesus monkeys. J Reprod Fertil 1975;42(1):1–7.

    PubMed  CAS  Google Scholar 

  15. Tompkins AB, Hutchinson P, de Kretser DM, Hedger MP. Characterization of lymphocytes in the adult rat testis by flow cytometry: effects of activin and transforming growth factor β on lymphocyte subsets in vitro. Biol Reprod 1998;58(4): 943–951.

    PubMed  CAS  Google Scholar 

  16. Miller SC. Localization of plutonium-241 in the testis. An interspecies comparison using light and electron microscope autoradiography. Int J Radiat Biol Relat Stud Phys Chem Med 1982;41(6):633–643.

    PubMed  CAS  Google Scholar 

  17. Miller SC, Bowman BM, Roberts LK. Identification and characterization of mononuclear phagocytes isolated from rat testicular interstitial tissues. J Leukoc Biol 1984;36(6):679–687.

    PubMed  CAS  Google Scholar 

  18. Hutson JC. Development of cytoplasmic digitations between Leydig cells and testicular macrophages of the rat. Cell Tissue Res 1992;267(2):385–389.

    PubMed  CAS  Google Scholar 

  19. Hutson JC, Stocco DM. Comparison of cellular and secreted proteins of macrophages from the testis and peritoneum on two-dimensional polyacrylamide gels: evidence of tissue specific function. Reg Immunol 1989;2(4):249–253.

    PubMed  CAS  Google Scholar 

  20. Wrobel KH, Dostal S, Schimmel M. Postnatal development of the tubular lamina propria and the intertubular tissue in the bovine testis. Cell Tissue Res 1988;252(3):639–653.

    PubMed  CAS  Google Scholar 

  21. Clemmons AJ, Thompson DL, Jr., Johnson L. Local initiation of spermatogenesis in the horse. Biol Reprod 1995;52(6): 1258–1267.

    PubMed  CAS  Google Scholar 

  22. Christensen AK, Gillman SW. The correlation of fine structure and function in steroid-secreting cells, with emphasis of those of the gonads. In: McKerns KW, ed. The Gonads. New York: Appleton-Century-Crofts;1969:415–488.

    Google Scholar 

  23. Miller SC, Bowman BM, Rowland HG. Structure, cytochemistry, endocytic activity, and immunoglobulin (Fc) receptors of rat testicular interstitial-tissue macrophages. Am J Anatomy 1983;168:1–13.

    CAS  Google Scholar 

  24. Hardy MP, Zirkin BR, Ewing LL. Kinetic studies on the development of the adult population of Leydig cells in testes of the pubertal rat. Endocrinology 1989;124(2):762–770.

    PubMed  CAS  Google Scholar 

  25. Niemi M, Sharpe RM, Brown WR. Macrophages in the interstitial tissue of the rat testis. Cell Tissue Res 1986;243(2): 337–344.

    PubMed  CAS  Google Scholar 

  26. Christensen AK, Gillim SW. The correlation of fine structure and function in steroid-secreting cells, with emphasis on those of the gonad. In: McKearns KW, ed. The gonads. New York: Appleton-Century-Crofts;1969:415–488.

    Google Scholar 

  27. Bambino TH, Hsueh AJ. Direct inhibitory effect of glucocorticoids upon testicular luteinizing hormone receptor and steroidogenesis in vivo and in vitro. Endocrinology 1981; 108(6):2142–2148.

    PubMed  CAS  Google Scholar 

  28. Miller SC, Bowman BM, Rowland HG. Structure, cytochemistry, endocytic activity, and immunoglobulin (Fc) receptors of rat testicular interstitial-tissue macrophages. Am J Anat 1983;168(1):1–13.

    PubMed  CAS  Google Scholar 

  29. Bergh A. Treatment with hCG increases the size of Leydig cells and testicular macrophages in unilaterally cryptorchid rats. Int J Androl 1987;10(6):765–772.

    PubMed  CAS  Google Scholar 

  30. Geierhaas B, Bornstein SR, Jarry H, Scherbaum WA, Herrmann M, Pfeiffer EF. Morphological and hormonal changes following vasectomy in rats, suggesting a functional role for Leydig-cell associated macrophages. Horm Metab Res 1991;23(8):373–378.

    PubMed  CAS  Google Scholar 

  31. Milewich L, Chen GT, Lyons C, Tucker TF, Uhr RW, MacDonald PC. Metabolism of androstenedione by guineapig peritoneal macrophages: synthesis of testosterone and 5α-reduced metabolites. J Steroid Biochemistry 1982;17:61–65.

    CAS  Google Scholar 

  32. Wang J, Wreford NG, Lan HY, Atkins R, Hedger MP. Leukocyte populations of the adult rat testis following removal of the Leydig cells by treatment with ethane dimethane sulfonate and subcutaneous testosterone implants. Biol Reprod 1994;51(3):551–561.

    PubMed  CAS  Google Scholar 

  33. Wei RQ, Yee JB, Straus DC, Hutson JC. Bactericidal activity of testicular macrophages. Biol Reprod 1988;38(4):830–835.

    PubMed  CAS  Google Scholar 

  34. Hedger MP, Eddy EM. The heterogeneity of isolated adult rat Leydig cells separated on Percoll density gradients: an immunological, cytochemical, and functional analysis. Endocrinology 1987;121(5):1824–1838.

    PubMed  CAS  Google Scholar 

  35. Sasmono RT, Oceandy D, Pollard JW, et al. A macrophage colony-stimulating factor receptor-green fluorescent protein transgene is expressed throughout the mononuclear phagocyte system of the mouse. Blood 2003;101(3):1155–1163.

    PubMed  CAS  Google Scholar 

  36. Kern S, Maddocks S. Indomethacin blocks the immunosuppressive activity of rat testicular macrophages cultured in vitro. J Reprod Immunol 1995;28(3):189–201.

    PubMed  CAS  Google Scholar 

  37. Hedger MP. Macrophages and the immune responsiveness of the testis. J Reprod Immunol 2002;57(1-2):19–34.

    PubMed  CAS  Google Scholar 

  38. Cohen JH, Danel L, Cordier G, Saez S, Revillard JP. Sex steroid receptors in peripheral T cells: absence of androgen receptors and restriction of estrogen receptors to OKT8-positive cells. J Immunol 1983;131(6):2767–2771.

    PubMed  CAS  Google Scholar 

  39. Gaytan F, Bellido C, Aguilar E, van Rooijen N. Requirement for testicular macrophages in Leydig cell proliferation and differentiation during prepubertal development in rats. J Reprod Fertil 1994;102(2):393–399.

    PubMed  CAS  Google Scholar 

  40. Gaytan F, Bellido C, Morales C, Garcia M, van Rooijen N, Aguilar E. In vivo manipulation (depletion versus activation) of testicular macrophages: central and local effects. J Endocrinol 1996;150(1):57–65.

    PubMed  CAS  Google Scholar 

  41. Kern S, Robertson SA, Mau VJ, Maddocks S. Cytokine secretion by macrophages in the rat testis. Biol Reprod 1995;53(6): 1407–1416.

    PubMed  CAS  Google Scholar 

  42. O’Bryan MK, Gerdprasert O, Nikolic-Paterson DJ, et al. Cytokine profiles in the testes of rats treated with lipopolysaccharide reveal localized suppression of inflammatory responses. Am J Physiol 2005;288:R1744–R1755.

    CAS  Google Scholar 

  43. Xiong Y, Hales DB. Expression, regulation, and production of tumor necrosis factor-α in mouse testicular interstitial macrophages in vitro. Endocrinology 1993;133(6):2568–2573.

    PubMed  CAS  Google Scholar 

  44. Hales DB, Xiong Y, Tur-Kaspa I. The role of cytokines in the regulation of Leydig cell P450cl7 gene expression. J Steroid Biochem Mol Biol 1992;43:907–914.

    CAS  Google Scholar 

  45. Gerdprasert O, O’Bryan MK, Muir JA, et al. The response of testicular leukocytes to lipopolysaccharide-induced inflammation: further evidence for heterogeneity of the testicular macrophage population. Cell Tissue Res 2002;308(2): 277–285.

    PubMed  CAS  Google Scholar 

  46. Buch JP, Havlovec SK. Variation in sperm penetration assay related to viral illness. Fertil Steril 1991;55(4):844–846.

    PubMed  CAS  Google Scholar 

  47. Cutolo M, Balleari E, Giusti M, Monachesi M, Accardo S. Sex hormone status of male patients with rheumatoid arthritis: evidence of low serum concentrations of testosterone at baseline and after human chorionic gonadotropin stimulation. Arthritis Rheum 1988;31(10):1314–1317.

    PubMed  CAS  Google Scholar 

  48. Adamopoulos DA, Lawrence DM, Vassilopoulos P, Contoyiannis PA, Swyer GI. Pituitary-testicular interrelationships in mumps orchitis and other viral infections. Br Med J 1978; 1(6121):1177–1180.

    PubMed  CAS  Google Scholar 

  49. Wallgren M, Kindahl H, Rodriguez-Martinez H. Alterations in testicular function after endotoxin injection in the boar. Int J Androl 1993;16(3):235–243.

    PubMed  CAS  Google Scholar 

  50. Wallgren M. Clinical, endocrinological and spermatological studies after endotoxin injection in the boar. Zentralbl Veterinarmed A 1989;36(9):664–675.

    Google Scholar 

  51. Wallgren M, Kindahl H, Larsson K. Clinical, endocrinological and spermatological studies after endotoxin in the ram. Zentralbl Veterinarmed A 1989;36(2):90–103.

    PubMed  CAS  Google Scholar 

  52. Tulassay Z, Viczian M, Bojthe L, Czeizel A. Quantitative histological studies on the injury of spermatogenesis induced by endotoxin in rats. J Reprod Fertil 1970;22(1):161–164.

    PubMed  CAS  Google Scholar 

  53. Harris SG, Padilla J, Koumas L, Ray D, Phipps RP. Prostaglandins as modulators of immunity. Trends Immunol 2002;23(3): 144–150.

    PubMed  CAS  Google Scholar 

  54. Bogdan C. Nitric oxide and the immune response. Nat Immunol 2001;2(10):907–916.

    PubMed  CAS  Google Scholar 

  55. Allen JA, Diemer T, Janus P, Held Hales K, Hales DB. Bacterial endotoxin lipopolysaccharide and reactive oxygen species inhibit Leydig cell steroidogenesis via perturbation of mitochondria. Endocrine 2005; in press.

    Google Scholar 

  56. Diemer T, Allen JA, Hales KH, Hales DB. Reactive oxygen disrupts mitochondria in MA-10 tumor Leydig cells and inhibits steroidogenic acute regulatory (StAR) protein and steroidogenesis. Endocrinology 2003;144(7):2882–2891.

    PubMed  CAS  Google Scholar 

  57. Hales KH, Diemer T, Ginde S, et al. Diametric effects of bacterial endotoxin lipopolysaccharide on adrenal and Leydig cell steroidogenic acute regulatory protein. Endocrinology 2000;141(11):4000–4012.

    PubMed  CAS  Google Scholar 

  58. Stocco DM, Wells J, Clark BJ.The effects of hydrogen peroxide on steroidogenesis in mouse Leydig tumor cells. Endocrinology 1993;133(6):2827–2832.

    PubMed  CAS  Google Scholar 

  59. Hedger MP, Meinhardt A. Cytokines and the immune-testicular axis. J Reprod Immunol 2003;58(1):1–26.

    PubMed  CAS  Google Scholar 

  60. Ogilvie K, Rivier C. The intracerebroventricular injection of interleukin-1β blunts the testosterone response to human chorionic gonadotropin: role of prostaglandin-and adrenergicdependent pathways. Endocrinology 1998;139(7):3088–3095.

    PubMed  CAS  Google Scholar 

  61. Turnbull AV, Rivier C. Inhibition of gonadotropin-induced testosterone secretion by the intracerebroventricular injection of interleukin-lβ in the male rat. Endocrinology 1997;138(3):1008–1013.

    PubMed  CAS  Google Scholar 

  62. Vergouwen RP, Huiskamp R, Bas RJ, Roepers-Gajadien HL, Davids JA, de Rooij DG. Postnatal development of testicular cell populations in mice. J Reprod Fertil 1993;99(2): 479–485.

    PubMed  CAS  Google Scholar 

  63. Raburn DJ, Coquelin A, Reinhart AJ, Hutson JC. Regulation of the macrophage population in postnatal rat testis. J Reprod Immunol 1993;24(2):139–151.

    PubMed  CAS  Google Scholar 

  64. Gaytan F, Bellido C, Aguilar E, van Rooijen N. Pituitary-testicular axis in rats lacking testicular macrophages. Eur J Endocrinol 1995;132(2):218–222.

    PubMed  CAS  Google Scholar 

  65. Gaytan F, Bellido C, Morales C, Reymundo C, Aguilar E, Van Rooijen N. Effects of macrophage depletion at different times after treatment with ethylene dimethane sulfonate (EDS) on the regeneration of Leydig cells in the adult rat. J Androl 1994;15(6):558–564.

    PubMed  CAS  Google Scholar 

  66. Gaytan F, Bellido C, Morales C, Reymundo C, Aguilar E, van Rooijen N. Selective depletion of testicular macrophages and prevention of Leydig cell repopulation after treatment with ethylene dimethane sulfonate in rats. J Reprod Fertil 1994;101(1):175–182.

    PubMed  CAS  Google Scholar 

  67. Cohen PE, Chisholm O, Arceci RJ, Stanley ER, Pollard JW. Absence of colony-stimulating factor-1 in osteopetrotic (csfmop/ csfmop) mice results in male fertility defects. Biol Reprod 1996;55(2):310–317.

    PubMed  CAS  Google Scholar 

  68. Cohen PE, Hardy MP, Pollard JW. Colony-stimulating factor-1 plays a major role in the development of reproductive function in male mice. Mol Endocrinol 1997;11(11): 1636–1650.

    PubMed  CAS  Google Scholar 

  69. Khan SA, Khan SJ, Dorrington JH. Interleukin-1 stimulates deoxyribonucleic acid synthesis in immature rat Leydig cells in vitro. Endocrinology 1992;131(4):1853–1857.

    PubMed  CAS  Google Scholar 

  70. Wang G, Hardy MP. Development of leydig cells in the insulin-like growth factor-I (igf-I) knockout mouse: effects of igf-I replacement and gonadotropic stimulation. Biol Reprod 2004;70(3):632–639.

    PubMed  CAS  Google Scholar 

  71. Arkins S, Rebeiz N, Brunke-Reese DL, Biragyn A, Kelley KW Interferon-γ inhibits macrophage insulin-like growth factor-I synthesis at the transcriptional level. Mol Endocrinol 1995; 9(3):350–360.

    PubMed  CAS  Google Scholar 

  72. Lukyanenko YO, Chen JJ, Hutson JC. Production of 25-hydroxycholesterol by testicular macrophages and its effects on Leydig cells. Biol Reprod 2001;64(3):790–796.

    PubMed  CAS  Google Scholar 

  73. Nes WD, Lukyanenko YO, Jia ZH, et al. Identification of the lipophilic factor produced by macrophages that stimulates steroidogenesis. Endocrinology 2000;141(3):953–958.

    PubMed  CAS  Google Scholar 

  74. Lukyanenko Y, Chen JJ, Hutson JC. Testosterone regulates 25-hydroxycholesterol production in testicular macrophages. Biol Reprod 2002;67(5):1435–1438.

    PubMed  CAS  Google Scholar 

  75. Chen JJ, Lukyanenko Y, Hutson JC. 25-hydroxycholesterol is produced by testicular macrophages during the early postnatal period and influences differentiation of Leydig cells in vitro. Biol Reprod 2002;66(5):1336–1341.

    PubMed  CAS  Google Scholar 

  76. Haider SG. Cell biology of Leydig cells in the testis. Int Rev Cytol 2004;233:181–241.

    PubMed  CAS  Google Scholar 

  77. Giannessi F, Giambelluca MA, Scavuzzo MC, Ruffoli R. Ultrastructure of testicular macrophages in aging mice. J Morphol 2005;263(1):39–46.

    PubMed  Google Scholar 

  78. Dinarello CA. Biologic basis for interleukin-1 in disease. Blood 1996;87(6):2095–2147.

    PubMed  CAS  Google Scholar 

  79. Stylianou E, Saklatvala J. Interleukin-1. Int J Biochem Cell Biol 2000;30:1075–1079.

    Google Scholar 

  80. Watanabe N, Kobayashi Y Selective release of a processed form of interleukin-1α. Cytokine 1994;6(6):597–601.

    PubMed  CAS  Google Scholar 

  81. Hazuda DJ, Lee JC, Young PR. The kinetics of interleukin 1 secretion from activated monocytes. Differences between interleukin-1α and interleukin-lβ. J Biol Chem 1988; 263(17):8473–8479.

    PubMed  CAS  Google Scholar 

  82. Black RA, Kronheim SR, Cantrell M, et al. Generation of biologically active interleukin-lβ by proteolytic cleavage of the inactive precursor. J Biol Chem 1988;263(19):9437–9442.

    PubMed  CAS  Google Scholar 

  83. Schonbeck U, Mach F, Libby P. Generation of biologically active IL-1 beta by matrix metalloproteinases: a novel caspase-1-independent pathway of IL-1 beta processing. J Immunol 1998;161(7):3340–3346.

    PubMed  CAS  Google Scholar 

  84. Fitzgerald KA, O’Neill LA. The role of the interleukin-1/Toll-like receptor superfamily in inflammation and host defence. Microbes Infect 2000;2(8):933–943.

    PubMed  CAS  Google Scholar 

  85. Sims JE, Gayle MA, Slack JL, et al. Interleukin 1 signaling occurs exclusively via the type I receptor. Proc Natl Acad Sci USA 1993;90(13):6155–6159.

    PubMed  CAS  Google Scholar 

  86. Eisenberg SP, Evans RJ, Arend WP, et al. Primary structure and functional expression from complementary DNA of a human interleukin-1 receptor antagonist. Nature 1990; 343(6256):341–346.

    PubMed  CAS  Google Scholar 

  87. Arend WP. Interleukin-1 receptor antagonist. Adv Immunol 1993;54:167–227.

    PubMed  CAS  Google Scholar 

  88. Svechnikov KV, Sultana T, Söder O. Age-dependent stimulation of Leydig cell steroidogenesis by interleukin-1 isoforms. Mol Cell Endocrinol 2001; 182(2): 193–201.

    PubMed  CAS  Google Scholar 

  89. Xiong Y, Hales DB. Immune-endocrine interactions in the mouse testis: cytokine-mediated inhibition of Leydig cell steroidogenesis. Endocrine J 1994;2(3):223–228.

    CAS  Google Scholar 

  90. Hales DB. Interleukin-1 inhibits Leydig cell steroidogenesis primarily by decreasing 17α-hydroxylase/C17-20 lyase cytochrome P450 expression. Endocrinology 1992;131(5): 2165–2172.

    PubMed  CAS  Google Scholar 

  91. Bergh A, Söder O. Interleukin-1β, but not interleukin-1α, induces acute inflammation-like changes in the testicular microcirculation of adult rats. J Reprod Immunol 1990; 17(2):155–165.

    PubMed  CAS  Google Scholar 

  92. Verhoeven G, Caillea J, Van Damme J, Billiau A. Interleukin-1 stimulates steroidogenesis in cultured rat Leydig cells. Mol Cell Endocrinol 1988;57(1-2):51–60.

    PubMed  CAS  Google Scholar 

  93. Calkins JH, Sigel MM, Nankin HR, Lin T. Interleukin-1 inhibits Leydig cell steroidogenesis in primary culture. Endocrinology 1988;123(3):1605–1610.

    PubMed  CAS  Google Scholar 

  94. Mauduit C, Chauvin MA, Hartmann DJ, Revol A, Morera AM, Benahmed M. Interleukin-1α as a potent inhibitor of gonadotropin action in porcine Leydig cells: site(s) of action. Biol Reprod 1992;46(6):1119–1126.

    PubMed  CAS  Google Scholar 

  95. Moore C, Moger WH. Interleukin-1α-induced changes in androgen and cyclic adenosine 3′,5′-monophosphate release in adult rat Leydig cells in culture. J Endocrinol 1991;129(3): 381–390.

    PubMed  CAS  Google Scholar 

  96. Calkins JH, Guo H, Sigel MM, Lin T. Differential effects of recombinant interleukin-1α and β on Leydig cell function. Biochem Biophys Res Comm 1990;167(2):548–553.

    PubMed  CAS  Google Scholar 

  97. Diemer T, Hales DB, Weidner W. Immune-endocrine interactions and Leydig cell function: the role of cytokines. Andrologia 2003;35(1):55–63.

    PubMed  CAS  Google Scholar 

  98. Lin T, Wang TL, Nagpal ML, Calkins JH, Chang WW, Chi R. Interleukin-1 inhibits cholesterol side-chain cleavage cytochrome P450 expression in primary cultures of Leydig cells. Endocrinology 1991;129(3):1305–1311.

    PubMed  CAS  Google Scholar 

  99. Lin T, Wang D, Stocco DM. Interleukin-1 inhibits Leydig cell steroidogenesis without affecting steroidogenic acute regulatory protein messenger ribonucleic acid or protein levels. J Endocrinol 1998;156(3):461–467.

    PubMed  CAS  Google Scholar 

  100. Wang X, Dyson MT, Jo Y, Stocco DM. Inhibition of cyclooxygenase-2 activity enhances steroidogenesis and steroidogenic acute regulatory gene expression in MA-10 mouse Leydig cells. Endocrinology 2003;144(8):3368–3375.

    PubMed  CAS  Google Scholar 

  101. Romanelli F, Valenca M, Conte D, Isidori A, Negro-Vilar A. Arachidonic acid and its metabolites effects on testosterone production by rat Leydig cells. J Endocrinol Invest 1995; 18(3):186–193.

    PubMed  CAS  Google Scholar 

  102. Colon E, Svechnikov KV, Carlsson-Skwirut C, Bang P, Soder O. Stimulation of steroidogenesis in immature rat Leydig cells evoked by interleukin-1α is potentiated by growth hormone and insulin-like growth factors. Endocrinology 2005;146(1): 221–230.

    PubMed  CAS  Google Scholar 

  103. Svechnikov K, Petersen C, Sultana T, et al. The paracrine role played by interleukin-1α in the testis. Curr Drug Targets Immune Endocr Metabol Disord 2004;4(1):67–74.

    PubMed  CAS  Google Scholar 

  104. Calandra T, Baumgartner JD, Grau GE, et al. Prognostic values of tumor necrosis factor/cachectin, interleukin-1, interferon-α, and interferon-γ in the serum of patients with septic shock. Swiss-Dutch J5 Immunoglobulin Study Group. J Infect Dis 1990;161(5):982–987.

    PubMed  CAS  Google Scholar 

  105. Spratt DI, Bigos ST, Beitins I, Cox P, Longcope C, Orav J. Both hyper-and hypogonadotropic hypogonadism occur transiently in acute illness: bio-and immunoactive gonadotropins. J Clin Endocrinol Metab 1992;75(6):1562–1570.

    PubMed  CAS  Google Scholar 

  106. Bruot BC, Clemens JW. Effect of adjuvant-induced arthritis on serum luteinizing hormone and testosterone concentrations in the male rat. Life Sci 1987;41:1559–1565.

    PubMed  CAS  Google Scholar 

  107. Bruot BC, Clemens JW. Regulation of testosterone production in the adjuvant-induced arthritic rat. J Androl 1992;13(1): 87–92.

    PubMed  CAS  Google Scholar 

  108. Clemens JW, Bruot BC. Testicular dysfunction in the adjuvant-induced arthritic rat. J Androl 1989;10(6):419–424.

    PubMed  CAS  Google Scholar 

  109. O’Bryan MK, Schlatt S, Phillips DJ, de Kretser DM, Hedger MP. Bacterial lipopolysaccharide-induced inflammation compromises testicular function at multiple levels in vivo. Endocrinology 2000;141(1):238–246.

    PubMed  CAS  Google Scholar 

  110. Sharma AC, Sam AD, 2nd, Lee LY, et al. Effect of NG-nitro-L-arginine methyl ester on testicular blood flow and serum steroid hormones during sepsis. Shock 1998;9(6): 416–421.

    PubMed  CAS  Google Scholar 

  111. Gow RM, O’Bryan MK, Canny BJ, Ooi GT, Hedger MP. Differential effects of dexamethasone treatment on lipopolysaccharide-induced testicular inflammation and reproductive hormone inhibition in adult rats. J Endocrinol 2001;168(1):193–201.

    PubMed  CAS  Google Scholar 

  112. Mealy K, Robinson B, Millette CF, Majzoub J, Wilmore DW. The testicular effects of tumor necrosis factor. Ann Surg 1990;211(4):470–475.

    PubMed  CAS  Google Scholar 

  113. van der Poll T, Romijn JA, Endert E, Sauerwein HP. Effects of tumor necrosis factor on the hypothalamic-pituitary-testicular axis in healthy men. Metabolism 1993;42(3):303–307.

    PubMed  Google Scholar 

  114. Meikle AW, Cardoso de Sousa JC, Ward JH, Woodward M, Samlowski WE. Reduction of testosterone synthesis after high dose interleukin-2 therapy of metastatic cancer. J Clin Endocrinol Metab 1991;73(5):931–935.

    PubMed  CAS  Google Scholar 

  115. Kasahara T, Hooks JJ, Dougherty SF, Oppenheim JJ. Interleukin-2-mediated immune interferon (IFN-γ) production by human T cells and T cell subsets. J Immunol 1983; 130(4): 1784–1789.

    PubMed  CAS  Google Scholar 

  116. Nedwin GE, Svedersky LP, Bringman TS, Palladino MAJ, Goeddel DV. Effect of interleukin-2, interferon-γ, and mitogens on the production of tumor necrosis factors a and β. J Immunol 1985;135(4):2492–2497.

    PubMed  CAS  Google Scholar 

  117. Tsigos C, Kyrou I, Chala E, et al. Circulating tumor necrosis factor a concentrations are higher in abdominal versus peripheral obesity. Metabolism 1999;48(10):1332–1335.

    PubMed  CAS  Google Scholar 

  118. Aggarwal BB, Pocsik E. Cytokines: From clone to clinic. Arch Biochem Biophys 1992;292(2):335–359.

    PubMed  CAS  Google Scholar 

  119. Cerami A. Inflammatory Cytokines. Clin Immunol Immunopathol 1992;62(1):S3–S10.

    PubMed  CAS  Google Scholar 

  120. Spooner CE, Markowitz NP, Sarvolatz LD. The role of tumor necrosis factor in sepsis. Clin Immunol Immunopathol 1992; 62(1):S11–S17.

    PubMed  CAS  Google Scholar 

  121. Mak T, Yeh W-C. Signaling for survival and apoptosis in the immune system. Arthritis Res 2002;4(Suppl 3):S243–S252.

    PubMed  Google Scholar 

  122. Hsu H, Shu HB, Pan MG, Goeddel DV. TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 1996;84(2):299–308.

    PubMed  CAS  Google Scholar 

  123. Moore C, Hutson JC. Physiological relevance of tumor necrosis factor in mediating macrophage-Leydig cell interactions. Endocrinology 1994;134(1):63–69.

    PubMed  CAS  Google Scholar 

  124. Warren DW, Pasupuleti V, Lu Y, Platler BW, Horton R. Tumor necrosis factor and interleukin-1 stimulate testosterone secretion in adult male rat Leydig cells in vitro. J Androl 1990;11(4):353–360.

    PubMed  CAS  Google Scholar 

  125. Calkins JH, Guo H, Sigel MM, Lin T. Tumor necrosis factor-α enhances inhibitory effects of interleukin-lβ on Leydig cell steroidogenesis. Biochem Biophys Res Comm 1990;166(3): 1313–1318.

    PubMed  CAS  Google Scholar 

  126. Xiong Y, Hales DB. The role of tumor necrosis factor-a in the regulation of mouse Leydig cell steroidogenesis. Endocrinology 1993;132(6):2438–2444.

    PubMed  CAS  Google Scholar 

  127. Mauduit C, Gasnier F, Rey C, et al. Tumor necrosis factor-α inhibits leydig cell steroidogenesis through a decrease in steroidogenic acute regulatory protein expression. Endocrinology 1998;139(6):2863–2868.

    PubMed  CAS  Google Scholar 

  128. Li X, Youngblood GL, Payne AH, Hales DB. Tumor necrosis factor-α inhibition of 17α-hydroxylase/C17-20 lyase gene (Cypl7) expression. Endocrinology 1995;136(8):3519–3526.

    PubMed  CAS  Google Scholar 

  129. Mauduit C, Hartmann DJ, Chauvin MA, Revol A, Morera AM, Benahmed M. Tumor necrosis factor a inhibits gonadotropin action in cultured porcine Leydig cells: site(s) of action. Endocrinology 1991;129(6):2933–2940.

    PubMed  CAS  Google Scholar 

  130. Budnik LT, Jahner D, Mukhopadhyay AK. Inhibitory effects of TNFα on mouse tumor Leydig cells: possible role of ceramide in the mechanism of action. Mol Cell Endocrinol 1999;150:39–46.

    PubMed  CAS  Google Scholar 

  131. Morales V, Santana P, Diaz R, et al. Intratesticular delivery of tumor necrosis factor-α and ceramide directly abrogates steroidogenic acute regulatory protein expression and Leydig cell steroidogenesis in adult rats. Endocrinology 2003; 144(11):4763–4772.

    PubMed  CAS  Google Scholar 

  132. Hong CY, Park JH, Ahn RS, et al. Molecular mechanism of suppression of testicular steroidogenesis by proinflammatory cytokine tumor necrosis factor a. Mol Cell Biol 2004;24(7): 2593–2604.

    PubMed  CAS  Google Scholar 

  133. Borden EC. Interferons: pleiotropic cellular modulators. Clin Immunol Immunopathol 1992;62(1):S18–S24.

    PubMed  CAS  Google Scholar 

  134. Orava M, Voutilainen R, Vihko R. Interferon-γ inhibits steroidogenesis and accumulation of mRNA of the steroidogenic enzymes, P450scc and P450c17 in cultured porcine Leydig cells. Mol Endocrinol 1989;3(6):887–894.

    PubMed  CAS  Google Scholar 

  135. Orava M, Cantell K, Vihko R. Human leukocyte interferon inhibits human chorionic gonadotropin stimulated testosterone production by porcine Leydig cells in culture. Biochem Biophys Res Comm 1985;127(3):809–815.

    PubMed  CAS  Google Scholar 

  136. Fountain S, Holland MK, Hinds LA, Janssens PA, Kerr PJ. Interstitial orchitis with impaired steroidogenesis and spermatogenesis in the testes of rabbits infected with an attenuated strain of myxoma virus. J Reprod Fertil 1997;110(1): 161–169.

    PubMed  CAS  Google Scholar 

  137. Hengge UR. Testosterone replacement for hypogonadism: clinical findings and best practices. AIDS Reader 2003;13(12 Suppl):S15–S21.

    PubMed  Google Scholar 

  138. Mauduit C, Goddard I, Besset V, et al. Leukemia inhibitory factor antagonizes gonadotropin induced-testosterone synthesis in cultured porcine leydig cells: sites of action. Endocrinology 2001;142(6):2509–2520.

    PubMed  CAS  Google Scholar 

  139. Guo H, Calkins JH, Sigel MM, Lin T. Interleukin-2 is a potent inhibitor of Leydig cell steroidogenesis. Endocrinology 1990;127(3): 1234–1239.

    PubMed  CAS  Google Scholar 

  140. Bornstein SR, Rutkowski H, Vrezas I. Cytokines and steroidogenesis. Mol Cell Endocrinol 2004;215(1-2):135–141.

    PubMed  CAS  Google Scholar 

  141. Avallet O, Vigier M, Perrard-Sapori MH, Saez JM. Transforming growth factor β inhibits Leydig cell functions. Biochem Biophys Res Comm 1987;146(2):575–581.

    PubMed  CAS  Google Scholar 

  142. Saez JM, Lejeune H. Regulation of Leydig cell functions by hormones and growth factors other than LH and IGF-1. In: Russell LD, ed. The Leydig Cell. Vienna, IL: Cache River Press 1996; 1:383–406.

    Google Scholar 

  143. Mayerhofer A. Leydig cell regulation by catecholamines and neuroendocrine messengers. In: Russell LD, ed. The Leydig Cell. Vienna, IL: Cache River Press, 1996;l:407–417.

    Google Scholar 

  144. Turnbull A, Rivier C. Brain-periphery connections: do they play a role in mediating the effect of centrally injected interleukin-1β on gonadal function. Neuroimmunomodulation 1995;2:224–235.

    PubMed  CAS  Google Scholar 

  145. Ulevitch RJ, Tobias PS. Receptor-dependent mechanisms of cell stimulation by bacterial endotoxin. Annu Rev Immunol 1995;13:437–457.

    PubMed  CAS  Google Scholar 

  146. Simonian NA, Coyle JT. Oxidative stress in neurodegenerative diseases. Annu Rev Pharmacol Toxicol 1996;36: 83–106.

    PubMed  CAS  Google Scholar 

  147. Quinn PG, Payne AH. Microsomal cytochrome P-450 enzyme damage in cultured Leydig cells: relation to steroidogenic desensitization. Ann NY Acad Sci 1984;438(7):649–651.

    PubMed  CAS  Google Scholar 

  148. Hornsby PJ. Physiological and pathological effects of steroids on the function of the adrenal cortex. Journal of Steroid Biochemistry 1987;27(4-6):1161–1171.

    PubMed  CAS  Google Scholar 

  149. Fernandez-Checa JC, Kaplowitz N, Garcia-Ruiz C, et al. GSH transport in mitochondria: defense against TNF-induced oxidative stress and alcohol-induced defect. Am J Physiol 1997;273(1 part 1):G7–G17.

    PubMed  CAS  Google Scholar 

  150. Diemer T, Held Hales K, Ginde S, et al. Immune activation via injection of bacterial lipopolysaccharide (LPS) in mice results in disruption of Leydig cell steroidogenesis due to oxidative mictochondrial damage. Biol Reprod 2000; 63(suppl):343.

    Google Scholar 

  151. Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991;43:109–142.

    PubMed  CAS  Google Scholar 

  152. McCall T, Vallance P. Nitric oxide takes centre-stage with newly defined roles. Trends Pharmacol Sci 1992; 13:1–6.

    PubMed  CAS  Google Scholar 

  153. Bredt DS, Snyder SH. Nitric Oxide: a physiologic messenger molecule. Annu Rev Biochem 1994;63:175–195.

    PubMed  CAS  Google Scholar 

  154. Ou J, Carlos TM, Watkins SC, et al. Differential effects of nonselective nitric oxide synthase (NOS) and selective inducible NOS inhibition on hepatic necrosis, apoptosis, ICAM-1 expression, and neutrophil accumulation during endotoxemia. Nitric Oxide 1997;1(5):404–416.

    PubMed  CAS  Google Scholar 

  155. Parratt JR. Nitric oxide in sepsis and endotoxaemia. J Antimicrob Chemother 1998;41(Suppl A):31–39.

    PubMed  CAS  Google Scholar 

  156. Thiemermann C. Nitric oxide and septic shock. Gen Pharmacol 1997;29(2):159–166.

    PubMed  CAS  Google Scholar 

  157. Forstermann U, Kleinert H. Nitric oxide synthase: expression and expressional control of the three isoforms. Naunyn Schmiedebergs Arch Pharmacol 1995;352(4):351–364.

    PubMed  CAS  Google Scholar 

  158. Huang PL, Lo EH. Genetic analysis of NOS isoforms using nNOS and eNOS knockout animals. Prog Brain Res 1998;118:13–25.

    PubMed  CAS  Google Scholar 

  159. Fukuto JM, Chaudhuri G. Inhibition of constitutive and inducible nitric oxide synthase: potential selective inhibition. Annu Rev Pharmacol Toxicol 1995;35:165–194.

    PubMed  CAS  Google Scholar 

  160. Salvemini D, Korbut R, Anggard E, Vane J. Immediate release of a nitric oxide-like factor from bovine aortic endothelial cells by Escherichia coli lipopolysaccharide. Proc Natl Acad Sci USA 1990;87(7):2593–2597.

    PubMed  CAS  Google Scholar 

  161. Thiemermann C, Wu C-C, Szabo C, Perreti M, Vane JR. Role of tumor necrosis factor in the induction of nitric oxide synthase in a rat model of endotoxin shock. Br J Pharmacol 1993;110(1-2): 177–182.

    PubMed  CAS  Google Scholar 

  162. Tracey WR, Tse J, Carter G. Lipopolysaccharide-induced changes in plasma nitrite and nitrate concentrations in rats and mice: pharmacological evaluation of nitric oxide synthase inhibitors. J Pharmacol Exp Ther 1995;272(3):1011–1015.

    PubMed  CAS  Google Scholar 

  163. Adams ML, Meyer ER, Sewing BN, Cicero TJ. Effects of nitric oxide-related agents on rat testicular function. J Pharmacol Exp Ther 1994;269(1):230–2307.

    PubMed  CAS  Google Scholar 

  164. Del Punta K, Charreau EH, Pignataro OP. Nitric oxide inhibits Leydig cell steroidogenesis. Endocrinology 1996;137(12): 5337–5343.

    Google Scholar 

  165. Bauché F, Stéphan JP, Touzalin AM, Jégou B. In vitro regulation of an inducible-type NO synthase in the rat seminiferous tubule cells. Biol Reprod 1998;58(2):431–438.

    PubMed  Google Scholar 

  166. O’Bryan MK, Schlatt S, Gerdprasert O, Phillips DJ, de Kretser DM, Hedger MP. Inducible nitric oxide synthase in the rat testis: evidence for potential roles in both normal function and inflammation-mediated infertility. Biol Reprod 2000;63(5):1285–1293.

    PubMed  CAS  Google Scholar 

  167. Gaytán F, Bellido C, Aguilar R, Morales C, van Rooijen N, Aguilar E. Role of the testis in the response of the pituitary-testicular axis to nitric oxide-related agents. Eur J Endocrinol 1997;137(3):301–308.

    PubMed  Google Scholar 

  168. Adams ML, Meyer ER, Cicero TJ. Effects of nitric oxiderelated agents on opioid regulation of rat testicular steroidogenesis. Biol Reprod 1996;54(5):1128–1134.

    PubMed  CAS  Google Scholar 

  169. Adams ML, Meyer ER, Sewing BN, Cicero TJ. Effects of nitric oxide-related agents on rat testicular function. J Pharmacol Exp Ther 1994;269(1):230–237.

    PubMed  CAS  Google Scholar 

  170. Pomerantz DK, Pitelka V. Nitric oxide is a mediator of the inhibitory effect of activated macrophages on production of androgen by the Leydig cell of the mouse. Endocrinology 1998;139(3):922–931.

    PubMed  CAS  Google Scholar 

  171. Welch C, Watson ME, Poth M, Hong T, Francis GL. Evidence to suggest nitric oxide is an interstitial regulator of Leydig cell steroidogenesis. Metab Clin Exp 1995;44(2):234–238.

    PubMed  CAS  Google Scholar 

  172. Kostic T, Andric S, Kovacevic R, Maric D. The involvement of nitric oxide in stress-impaired testicular steroidogenesis. Eur J Pharmacol 1998;346(2-3):267–273.

    PubMed  CAS  Google Scholar 

  173. Sharma A, Motew S, Farias S, et al. Sepsis alters myocardial and plasma concentrations of endothelin and nitric oxide in rats. J Mol Cell Cardiol 1997;29:1469–1477.

    PubMed  CAS  Google Scholar 

  174. Koppenol WH, Moreno JJ, Pryor WA, Ischiropoulos H, Beckman JS. Peroxynitrite, a cloaked oxidant formed by nitric oxide and Superoxide. Chem Res Toxicol 1992;5(6):834–842.

    PubMed  CAS  Google Scholar 

  175. Ischiropoulos H, Zhu L, Chen J, et al. Peroxynitrite-mediated tyrosine nitration catalyzed by Superoxide dismutase. Arch Biochem Biophys 1992;298(2):431–437.

    PubMed  CAS  Google Scholar 

  176. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 1990;87(4):1620–1624.

    PubMed  CAS  Google Scholar 

  177. Guidarelli A, Clementi E, Sciorati C, Cantoni O. The mechanism of the nitric oxide-mediated enhancement of tertbutylhydroperoxide-induced DNA single strand breakage. Br J Pharmacol 1998;125(5):1074–1080.

    PubMed  CAS  Google Scholar 

  178. Lissbrant E, Lofmark U, Collin O, Bergh A. Is nitric oxide involved in the regulation of the rat testicular vasculature? Biol Reprod 1997;56(5):1221–1227.

    PubMed  CAS  Google Scholar 

  179. Weissman BA, Niu E, Ge R, et al. Paracrine modulation of androgen synthesis in rat leydig cells by nitric oxide. J Androl 2005;26(3):369–378.

    PubMed  CAS  Google Scholar 

  180. Gerdprasert O, O’Bryan MK, Muir JA, et al. The response of testicular leukocytes to lipopolysaccharide-induced inflammation: further evidence for heterogeneity of the testicular macrophage population. Cell Tissue Res 2002;308(2):277–285.

    PubMed  CAS  Google Scholar 

  181. O’Bryan MK, Schlatt S, Gerdprasert O, Phillips DJ, de Kretser DM, Hedger MP. Inducible nitric oxide synthase in the rat testis: evidence for potential roles in both normal function and inflammation-mediated infertility. Biol Reprod 2000;63(5):1285–1293.

    PubMed  CAS  Google Scholar 

  182. Wang Y, Goligorsky MS, Lin M, Wilcox JN, Marsden PA. A novel, testis-specific mRNA transcript encoding an NH2-terminal truncated nitric-oxide synthase. J Biol Chem 1997; 272(17):11,392–11,401.

    CAS  Google Scholar 

  183. Herman M, Rivier C. Activation of a neural brain-testicular pathway rapidly lowers Leydig cell levels of the steroidogenic acute regulatory protein and the peripheral-type benzodiazepine receptor while increasing levels of neuronal nitric oxide synthase. Endocrinology 2006;147(1):624–633.

    PubMed  CAS  Google Scholar 

  184. Zini A, Abitbol J, Girardi SK, Schulsinger D, Goldstein M, Schlegel PN. Germ cell apoptosis and endothelial nitric oxide synthase (eNOS) expression following ischemia-reperfusion injury to testis. Arch Androl 1998;41(1):57–65.

    PubMed  CAS  Google Scholar 

  185. Williams CS, Mann M, DuBois RN. The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 1999;18(55):7908–7916.

    PubMed  CAS  Google Scholar 

  186. Im JW, Kim HK, Kim ND, et al. Activation of cyclooxygenases by H2O2 and t-butylhydroperoxide in aged rat lung. Biotechnol Lett 2004;26(21):1665–1669.

    PubMed  CAS  Google Scholar 

  187. Williams CS, DuBois RN. Prostaglandin endoperoxide synthase: why two isoforms? Am J Physiol 1996;270(3 Part 1): G393–G400.

    PubMed  CAS  Google Scholar 

  188. Wang XJ, Dyson MT, Mondillo C, Patrignani Z, Pignataro O, Stocco DM. Interaction between arachidonic acid and cAMP signaling pathways enhances steroidogenesis and StAR gene expression in MA-10 Leydig tumor cells. Mol Cell Endocrinol 2002;188(1-2):55–63.

    PubMed  CAS  Google Scholar 

  189. Wang X, Walsh LP, Reinhart AJ, Stocco DM. The role of arachidonic acid in steroidogenesis and steroidogenic acute regulatory (StAR) gene and protein expression. J Biol Chem 2000;275(26):20,204–20,209.

    CAS  Google Scholar 

  190. Stocco DM, Wang X, Jo Y, Manna PR. Multiple Signaling Pathways Regulating Steroidogenesis and Steroidogenic Acute Regulatory Protein Expression: More Complicated than We Thought. Mol Endocrinol 2005;19(11):2647–2659.

    PubMed  CAS  Google Scholar 

  191. Gunnarsson D, Svensson M, Selstam G, Nordberg G. Pronounced induction of testicular PGF(2α) and suppression of testosterone by cadmium-prevention by zinc. Toxicology 2004;200(1):49–58.

    PubMed  CAS  Google Scholar 

  192. Romanelli F, Valenca M, Conte D, Isidori A, Negro-Vilar A. Arachidonic acid and its metabolites effects on testosterone production by rat Leydig cells. J Endocrinol Invest 1995; 18(3): 186–193.

    PubMed  CAS  Google Scholar 

  193. Sairam MR. Effects of prostaglandins on the action of luteinizing hormone in dispersed rat intestitial cells. Prostaglandins 1979;17(6):929–937.

    PubMed  CAS  Google Scholar 

  194. 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(1-2):161–170.

    PubMed  CAS  Google Scholar 

  195. Diaz FJ, Anderson LE, Wu YL, Rabot A, Tsai SJ, Wiltbank MC. Regulation of progesterone and prostaglandin F2α production in the CL. Mol Cell Endocrinol 2002;191(1):65–80.

    PubMed  CAS  Google Scholar 

  196. Janssen-Heininger YM, Poynter ME, Baeuerle PA. Recent advances towards understanding redox mechanisms in the activation of nuclear factor κB. Free Radic Biol Med 2000;28(9):1317–1327.

    PubMed  CAS  Google Scholar 

  197. Pahl HL, Baeuerle PA. Oxygen and the control of gene expression. Bioessays 1994;16(7):497–502.

    PubMed  CAS  Google Scholar 

  198. Baeuerle PA, Henkel T. Function and activation of NF-kappa B in the immune system. Annu Rev Immunol 1994; 12: 141–179.

    PubMed  CAS  Google Scholar 

  199. Chung HY, Kim HJ, Kim JW, Yu BP. The inflammation hypothesis of aging: molecular modulation by calorie restriction. Ann NY Acad Sci 2001;928:327–335.

    PubMed  CAS  Google Scholar 

  200. Morley JE, Baumgartner RN. Cytokine-related aging process. J Gerontol A Biol Sci Med Sci 2004;59(9):M924–M929.

    PubMed  Google Scholar 

  201. Plowden J, Renshaw-Hoelscher M, Engleman C, Katz J, Sambhara S. Innate immunity in aging: impact on macrophage function. Aging Cell 2004;3(4):161–167.

    PubMed  CAS  Google Scholar 

  202. Lloberas J, Celada A. Effect of aging on macrophage function. Exp Gerontol 2002;37(12):1325–1331.

    PubMed  CAS  Google Scholar 

  203. Wang X, Stocco DM. The decline in testosterone biosynthesis during male aging: a consequence of multiple alterations. Mol Cell Endocrinol 2005;238(1-2):1–7.

    PubMed  CAS  Google Scholar 

  204. Wang X, Shen CL, Dyson MT, et al. Cyclooxygenase-2 regulation of the age-related decline in testosterone biosynthesis. Endocrinology 2005; 146:4202–4208.

    PubMed  CAS  Google Scholar 

  205. Kim HJ, Kim KW, Yu BP, Chung HY. The effect of age on cyclooxygenase-2 gene expression: NF-κB activation and IκBβ degradation. Free Radic Biol Med 2000;28(5):683–692.

    PubMed  CAS  Google Scholar 

  206. Baek BS, Kim JW, Lee JH, et al. Age-related increase of brain cyclooxygenase activity and dietary modulation of oxidative status. J Gerontol A Biol Sci Med Sci 2001;56(10): B426–B431.

    PubMed  CAS  Google Scholar 

  207. Hayek MG, Mura C, Wu D, et al. Enhanced expression of inducible cyclooxygenase with age in murine macrophages. J Immunol 1997;159(5):2445–2451.

    PubMed  CAS  Google Scholar 

  208. Giannessi F, Giambelluca MA, Scavuzzo MC, Ruffoli R. Ultrastructure of testicular macrophages in aging mice. J Morphol 2005;263(1):39–46.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL

    Dale B. Hales PhD

Authors
  1. Dale B. Hales PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA

    Anita H. Payne PhD

  2. Center for Biomedical Research, Population Council, New York, NY

    Matthew P. Hardy PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Hales, D.B. (2007). Regulation of Leydig Cell Function as it Pertains to the Inflammatory Response. In: Payne, A.H., Hardy, M.P. (eds) The Leydig Cell in Health and Disease. Contemporary Endocrinology. Humana Press. https://doi.org/10.1007/978-1-59745-453-7_21

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-453-7_21

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-754-9

  • Online ISBN: 978-1-59745-453-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation