Skip to main content
SpringerLink
Log in

Neuroendocrine Control of Testicular Function

  • Chapter
Male Hypogonadism

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

  • 178 Accesses

Abstract

The proximate regulator of testicular function is gonadotropin-releasing hormone (GnRH), which is produced in neurons scattered throughout the anterior hypothalamus. When it reaches the anterior pituitary, GnRH stimulates the synthesis and secretion of the pituitary gonadotropic hormones, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). LH and FSH are released into the circulation in bursts and activate G protein-coupled receptors (GPCRs) on Leydig and Sertoli cells, respectively, that stimulate testosterone production and spermatogenesis. The system is tightly regulated and is maintained at a proper set point by the negative feedback effects of testicular steroids and inhibin-B. Testicular function is also influenced by multiple internal and external environmental factors.

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 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight 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. Goldsmith PC, Song T, Kim EJ, Boggan JE. Location of the neuroendocrine gonadotropin-releasing hormone neurons in the monkey hypothalamus by retrograde tracing and immunostaining. J Neuroendocrinol 1990; 2: 157–168.

    Article  PubMed  CAS  Google Scholar 

  2. Kepa JK, Spaulding AJ, Jacobsen BM, et al. Structure of the distal human gonadotropin releasing hormone (hGnrh) gene promoter and functional analysis in Gt1–7 neuronal cells. Nucleic Acids Res 1996; 24: 3614–3620.

    Article  PubMed  CAS  Google Scholar 

  3. El Majdoubi M, Sahu A, Plant TM. Changes in hypothalamic gene expression associated with the arrest of pulsatile gonadotropin-releasing hormone release during infancy in the agonadal male rhesus monkey (Macaca mulatta). Endocrinology 2000; 141: 3273–3277.

    Article  PubMed  Google Scholar 

  4. Caraty A, Locatelli A. Effect of time after castration on secretion of LHRH and LH in the ram. J Reprod Fertil 1988; 82: 263–269.

    Article  PubMed  CAS  Google Scholar 

  5. Knobil E. The electrophysiology of the GnRH pulse generator in the rhesus monkey. J Steroid Biochem 1989; 33: 669–671.

    Article  PubMed  CAS  Google Scholar 

  6. Krsmanovic LZ, Martinez-Fuentes AJ, Arora KK, et al. Local regulation of gonadotroph function by pituitary gonadotropin-releasing hormone. Endocrinology 2000; 141: 1187–1195.

    Article  PubMed  CAS  Google Scholar 

  7. Vazquez-Martinez R, Leclerc GM, Wierman ME, Boockfor FR. Episodic activation of the rat GnRH promoter: role of the homeoprotein oct-1. Mol Endocrinol 2002; 16: 2093–2100.

    Article  PubMed  CAS  Google Scholar 

  8. Urbanski HF, Kohama SG, Garyfallou VT. Mechanisms mediating the response of GnRH neurones to excitatory amino acids. Rev Reprod 1996; 1: 173–181.

    Article  PubMed  CAS  Google Scholar 

  9. White RB, Eisen JA, Kasten TL, Fernald RD. Second gene for gonadotropin-releasing hormone in humans. Proc Natl Acad Sci USA 1998; 95: 305–309.

    Article  PubMed  CAS  Google Scholar 

  10. Sherwood NM, Lovejoy DA, Coe IR. Origin of mammalian gonadotropin-releasing hormones. Endocr Rev 1993; 14: 241–254.

    PubMed  CAS  Google Scholar 

  11. Lescheid DW, Terasawa E, Abler LA, et al. A second form of gonadotropin-releasing hormone (GnRH) with characteristics of chicken GnRH-II is present in the primate brain. Endocrinology 1997; 138: 5618–5629.

    Article  PubMed  CAS  Google Scholar 

  12. Neill JD, Duck LW, Sellers JC, Musgrove LC. A gonadotropin-releasing hormone (GnRH) receptor specific for GnRH II in primates. Biochem Biophys Res Comm 2001; 282: 1012–1018.

    Article  PubMed  CAS  Google Scholar 

  13. van Biljon W, Wykes S, Scherer S, Krawetz SA, Hapgood J. Type II gonadotropin-releasing hormone receptor transcripts in human sperm. Biol Reprod 2002; 67: 1741–1749.

    Article  PubMed  CAS  Google Scholar 

  14. Childs GV. Division of labor among gonadotropes. Vitam Horm 1995; 50: 215–286.

    Article  PubMed  CAS  Google Scholar 

  15. Okada Y, Fujii Y, Moore JP, Jr., Winters SJ. Androgen receptors in gonadotrophs in pituitary cultures from adult male monkeys and rats. Endocrinology 2003; 144: 267–273.

    Article  PubMed  CAS  Google Scholar 

  16. Shacham S, Harris D, Ben-Shlomo H, et al. Mechanism of GnRH receptor signaling on gonadotropin release and gene expression in pituitary gonadotrophs. Vitam Horm 2001; 63: 63–90.

    Article  PubMed  CAS  Google Scholar 

  17. Stojilkovic SS, Reinhart J, Catt KJ. Gonadotropin-releasing hormone receptors: structure and signal transduction pathways. Endocr Rev 1994; 15: 462–499.

    PubMed  CAS  Google Scholar 

  18. Conn PM, Janovick JA, Stanislaus D, Kuphal D, Jennes L. Molecular and cellular bases of gonadotropin-releasing hormone action in the pituitary and central nervous system. Vitam Horm 1995; 50: 151–214.

    Article  PubMed  CAS  Google Scholar 

  19. Weck J, Anderson AC, Jenkins S, Fallest PC, Shupnik MA. Divergent and composite gonadotropinreleasing hormone-responsive elements in the rat luteinizing hormone subunit genes. Mol Endocrinol 2000; 14: 472–485.

    Article  PubMed  CAS  Google Scholar 

  20. Haisenleder DJ, Yasin M, Marshall JC. Gonadotropin subunit and gonadotropin-releasing hormone receptor gene expression are regulated by alterations in the frequency of calcium pulsatile signals. Endocrinology 1997; 138: 5227–5230.

    Article  PubMed  CAS  Google Scholar 

  21. Kaiser UB, Jakubowiak A, Steinberger A, Chin WW. Regulation of rat pituitary gonadotropin-releasing hormone receptor mRNA levels in vivo and in vitro. Endocrinology 1993; 133: 931–934.

    Article  PubMed  CAS  Google Scholar 

  22. Clayton RN, Catt KJ. Gonadotropin-releasing hormone receptors: characterization, physiological regulation, and relationship to reproductive function. Endocr Rev 1981; 2: 186–209.

    Article  PubMed  CAS  Google Scholar 

  23. Kaiser UB, Halvorson LM, Chen MT. Sp1, steroidogenic factor 1 (SF-1), and early growth response protein 1 (egr-1) binding sites form a tripartite gonadotropin-releasing hormone response element in the rat luteinizing hormone-beta gene promoter: an integral role for SF-1. Mol Endocrinol 2000; 14: 1235–1245.

    Article  PubMed  CAS  Google Scholar 

  24. Strahl BD, Huang HJ, Sebastian J, Ghosh BR, Miller WL. Transcriptional activation of the ovine follicle-stimulating hormone beta-subunit gene by gonadotropin-releasing hormone: involvement of two activating protein-1-binding sites and protein kinase C. Endocrinology 1998; 139: 4455–4465.

    Article  PubMed  CAS  Google Scholar 

  25. Maurer RA, Kim KE, Schoderbek WE, Roberson MS, Glenn DJ. Regulation of glycoprotein hormone alpha-subunit gene expression. Recent Prog Horm Res 1999; 54: 455–484.

    PubMed  CAS  Google Scholar 

  26. Chedrese PJ, Kay TW, Jameson JL. Gonadotropin-releasing hormone stimulates glycoprotein hormone alpha-subunit messenger ribonucleic acid (mRNA) levels in alpha T3 cells by increasing transcription and mRNA stability. Endocrinology 1994; 134: 2475–2481.

    Article  PubMed  CAS  Google Scholar 

  27. Xing Y, Williams C, Campbell RK, et al. Threading of a glycosylated protein loop through a protein hole: implications for combination of human chorionic gonadotropin subunits. Protein Sci 2001; 10: 226–235.

    Article  PubMed  CAS  Google Scholar 

  28. Belchetz PE, Plant TM, Nakai Y, Keogh EJ, Knobil E. Hypophysial responses to continuous and intermittent delivery of hypopthalamic gonadotropin-releasing hormone. Science 1978; 202: 631–633.

    Article  PubMed  CAS  Google Scholar 

  29. Nankin HR, Troen P. Repetitive luteinizing hormone elevations in serum of normal men. J Clin Endocrinol Metab 1971; 33: 558–560.

    Article  PubMed  CAS  Google Scholar 

  30. Crowley WF, Jr., McArthur JW. Simulation of the normal menstrual cycle in Kallman’s syndrome by pulsatile administration of luteinizing hormone-releasing hormone (LHRH). J Clin Endocrinol Metab 1980; 51: 173–175.

    Article  PubMed  Google Scholar 

  31. Labrie F. Endocrine therapy for prostate cancer. Endocrinol Metab Clin North Am 1991; 20: 845–872.

    PubMed  CAS  Google Scholar 

  32. Padmanabhan V, McFadden K, Mauger DT, Karsch FJ, Midgley AR, Jr. Neuroendocrine control of follicle-stimulating hormone (FSH) secretion. I. Direct evidence for separate episodic and basal components of FSH secretion. Endocrinology 1997; 138: 424–432.

    Article  PubMed  CAS  Google Scholar 

  33. Veldhuis JD, Johnson ML. Testing pulse detection algorithms with simulations of episodically pulsatile substrate, metabolite, or hormone release. Methods Enzymol 1994; 240: 377–415.

    Article  PubMed  CAS  Google Scholar 

  34. Spratt DI, Carr DB, Merriam GR, Scully RE, Rao PN, Crowley WF, Jr. The spectrum of abnormal patterns of gonadotropin-releasing hormone secretion in men with idiopathic hypogonadotropic hypogonadism: clinical and laboratory correlations. J Clin Endocrinol Metab 1987; 64: 283–291.

    Article  PubMed  CAS  Google Scholar 

  35. Boyar RM, Rosenfeld RS, Kapen S, et al. Human puberty. Simultaneous augmented secretion of luteinizing hormone and testosterone during sleep. J Clin Invest 1974; 54: 609–618.

    Article  PubMed  CAS  Google Scholar 

  36. Tenover JS, Matsumoto AM, Clifton DK, Bremner WJ. Age-related alterations in the circadian rhythms of pulsatile luteinizing hormone and testosterone secretion in healthy men. J Gerontol 1988; 43: M163–M169.

    Article  PubMed  CAS  Google Scholar 

  37. Luboshitzky R, Zabari Z, Shen-Orr Z, Herer P, Lavie P. Disruption of the nocturnal testosterone rhythm by sleep fragmentation in normal men. J Clin Endocrinol Metab 2001; 86: 1134–1139.

    Article  PubMed  CAS  Google Scholar 

  38. Bremner WJ, Vitiello MV, Prinz PN. Loss of circadian rhythmicity in blood testosterone levels with aging in normal men. J Clin Endocrinol Metab 1983; 56: 1278–1281.

    Article  PubMed  CAS  Google Scholar 

  39. Winters SJ. Diurnal rhythm of testosterone and luteinizing hormone in hypogonadal men. J Androl 1991; 12: 185–190.

    PubMed  CAS  Google Scholar 

  40. Payne AH, Youngblood GL. Regulation of expression of steroidogenic enzymes in Leydig cells. Biol Reprod 1995; 52: 217–225.

    Article  PubMed  CAS  Google Scholar 

  41. Dufau ML. The luteinizing hormone receptor. Annu Rev Physiol 1998; 60: 461–496.

    Article  PubMed  CAS  Google Scholar 

  42. Stocco DM. StAR protein and the regulation of steroid hormone biosynthesis. Annu Rev Physiol 2001; 63: 193–213.

    Article  PubMed  CAS  Google Scholar 

  43. Mannaerts B, de Leeuw R, Geelen J, et al. Comparative in vitro and in vivo studies on the biological characteristics of recombinant human follicle-stimulating hormone. Endocrinology 1991; 129: 2623–2630.

    Article  PubMed  CAS  Google Scholar 

  44. Majumdar SS, Winters SJ, Plant TM. A study of the relative roles of follicle-stimulating hormone and luteinizing hormone in the regulation of testicular inhibin secretion in the rhesus monkey (Macaca mulatta). Endocrinology 1997; 138: 1363–1373.

    Article  PubMed  CAS  Google Scholar 

  45. Vierhapper H, Nowotny P, Waldhausl W. Production rates of testosterone in patients with Cushing’s syndrome. Metabolism 2000; 49: 229–231.

    Article  PubMed  CAS  Google Scholar 

  46. Jones ME, Simpson ER. Oestrogens in male reproduction. Baillieres Best Pract Res Clin Endocrinol Metab 2000; 14: 505–516.

    Article  PubMed  CAS  Google Scholar 

  47. Brodie A, Inkster S, Yue W. Aromatase expression in the human male. Mol Cell Endocrinol 2001; 178: 23–28.

    Article  PubMed  CAS  Google Scholar 

  48. Simpson ER, Davis SR. Minireview: aromatase and the regulation of estrogen biosynthesis—some new perspectives. Endocrinology 2001; 142: 4589–4594.

    Article  PubMed  CAS  Google Scholar 

  49. Couse JF, Curtis Hewitt S, Korach KS. Receptor null mice reveal contrasting roles for estrogen receptor alpha and beta in reproductive tissues. J Steroid Biochem Mol Biol 2000; 74: 287–296.

    Article  PubMed  CAS  Google Scholar 

  50. Couse JF, Lindzey J, Grandien K, Gustafsson JA, Korach KS. Tissue distribution and quantitative analysis of estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) messenger ribonucleic acid in the wild-type and ERalpha-knockout mouse. Endocrinology 1997; 138: 4613–4621.

    Article  PubMed  CAS  Google Scholar 

  51. Grumbach MM, Auchus RJ. Estrogen: consequences and implications of human mutations in synthesis and action. J Clin Endocrinol Metab 1999; 84: 4677–4694.

    Article  PubMed  CAS  Google Scholar 

  52. Robertson KM, O’Donnell L, Jones ME, et al. Impairment of spermatogenesis in mice lacking a functional aromatase (cyp 19) gene. Proc Natl Acad Sci USA 1999; 96: 7986–7991.

    Article  PubMed  CAS  Google Scholar 

  53. Plant TM. Effects of orchidectomy and testosterone replacement treatment on pulsatile luteinizing hormone secretion in the adult rhesus monkey (Macaca mulatta). Endocrinology 1982; 110: 1905–1913.

    Article  PubMed  CAS  Google Scholar 

  54. Plant TM, Dubey AK. Evidence from the rhesus monkey (Macaca mulatta) for the view that negative feedback control of luteinizing hormone secretion by the testis is mediated by a deceleration of hypothalamic gonadotropin-releasing hormone pulse frequency. Endocrinology 1984; 115: 2145–2153.

    Article  PubMed  CAS  Google Scholar 

  55. Winters SJ, Kawakami S, Sahu A, Plant TM. Pituitary follistatin and activin gene expression, and the testicular regulation of FSH in the adult Rhesus monkey (Macaca mulatta). Endocrinology 2001; 142: 2874–2848.

    Article  PubMed  CAS  Google Scholar 

  56. Kawakami S, Winters SJ. Regulation of lutenizing hormone secretion and subunit messenger ribonucleic acid expression by gonadal steroids in perifused pituitary cells from male monkeys and rats. Endocrinology 1999; 140: 3587–3593.

    Article  PubMed  CAS  Google Scholar 

  57. Finkelstein JS, Whitcomb RW, O’Dea LS, Longcope C, Schoenfeld DA, Crowley WF, Jr. Sex steroid control of gonadotropin secretion in the human male. I. Effects of testosterone administration in normal and gonadotropin-releasing hormone-deficient men. J Clin Endocrinol Metab 1991; 73: 609–620.

    Article  PubMed  CAS  Google Scholar 

  58. Bagatell CJ, Dahl KD, Bremner WJ. The direct pituitary effect of testosterone to inhibit gonadotropin secretion in men is partially mediated by aromatization to estradiol. J Androl 1994; 15: 15–21.

    PubMed  CAS  Google Scholar 

  59. Naftolin F, Pujol-Amat P, Corker CS, et al. Gonadotropins and gonadal steroids in androgen insensitivity (testicular feminization) syndrome: effects of castration and sex steroid administration. Am J Obstet Gynecol 1983; 147: 491–496.

    PubMed  CAS  Google Scholar 

  60. Winters SJ, Troen P. Evidence for a role of endogenous estrogen in the hypothalamic control of gonadotropin secretion in men. J Clin Endocrinol Metab 1985; 61: 842–845.

    Article  PubMed  CAS  Google Scholar 

  61. Marynick SP, Loriaux DL, Sherins RJ, Pita JC, Jr., Lipsett MB. Evidence that testosterone can suppress pituitary gonadotropin secretion independently of peripheral aromatization. J Clin Endocrinol Metab 1979; 49: 396–398.

    Article  PubMed  CAS  Google Scholar 

  62. Smith EP, Boyd J, Frank GR, et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med 1994; 331: 1056–1061.

    Article  PubMed  CAS  Google Scholar 

  63. Morishima A, Grumbach MM, Simpson ER, Fisher C, Qin K. Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab 1995; 80: 3689–3698.

    Article  PubMed  CAS  Google Scholar 

  64. Carani C, Qin K, Simoni M, et al. Effect of testosterone and estradiol in a man with aromatase deficiency. N Engl J Med 1997; 337: 91–95.

    Article  PubMed  CAS  Google Scholar 

  65. Hayes FJ, Seminara SB, Decruz S, Boepple PA, Crowley WF, Jr. Aromatase inhibition in the human male reveals a hypothalamic site of estrogen feedback. J Clin Endocrinol Metab 2000; 85: 3027–3035.

    Article  PubMed  CAS  Google Scholar 

  66. Santen RJ, Bardin CW. Episodic luteinizing hormone secretion in man. Pulse analysis, clinical interpretation, physiologic mechanisms. J Clin Invest 1973; 52: 2617–2628.

    Article  PubMed  CAS  Google Scholar 

  67. Mather JP, Moore A, Li RH. Activins, inhibins, and follistatins: further thoughts on a growing family of regulators. Proc Soc Exp Biol Med 1997; 215: 209–222.

    PubMed  CAS  Google Scholar 

  68. Carroll RS, Corrigan AZ, Vale W, Chin WW. Activin stabilizes follicle-stimulating hormone-beta messenger ribonucleic acid levels. Endocrinology 1991; 129: 1721–1726.

    Article  PubMed  CAS  Google Scholar 

  69. Weiss J, Guendner MJ, Halvorson LM, Jameson JL. Transcriptional activation of the follicle-stimulating hormone beta-subunit gene by activin. Endocrinology 1995; 136: 1885–1891.

    Article  PubMed  CAS  Google Scholar 

  70. Suszko MI, Lo DJ, Suh H, Camper SA, Woodruff TK. Regulation of the rat follicle-stimulating hormone beta-subunit promoter by activin. Mol Endocrinol 2003; 17: 318–332.

    Article  PubMed  CAS  Google Scholar 

  71. McDowell N, Gurdon JB. Activin as a morphogen in Xenopus mesoderm induction. Sem Cell Dev Biol 1999; 10: 311–317.

    Article  CAS  Google Scholar 

  72. Munz B, Tretter YP, Hertel M, Engelhardt F, Alzheimer C, Werner S. The roles of activins in repair processes of the skin and the brain. Mol Cell Endocrinol 2001; 180: 169–177.

    Article  PubMed  CAS  Google Scholar 

  73. Phillips DJ, Jones KL, Scheerlinck JY, Hedger MP, de Kretser DM. Evidence for activin A and follistatin involvement in the systemic inflammatory response. Mol Cell Endocrinol 2001; 180: 155–162.

    Article  PubMed  CAS  Google Scholar 

  74. Plendl J. Angiogenesis and vascular regression in the ovary. Anat Histol Embryol 2000; 29: 257–266.

    Article  PubMed  CAS  Google Scholar 

  75. Pangas SA, Woodruff TK. Activin signal transduction pathways. Trends Endocrinol Metab 2000; 11: 309–314.

    Article  PubMed  CAS  Google Scholar 

  76. Mathews LS, Vale WW. Expression cloning of an activin receptor, a predicted transmembrane serine kinase. Cell 1991; 65: 973–982.

    Article  PubMed  CAS  Google Scholar 

  77. Mathews LS, Vale WW, Kintner CR. Cloning of a second type of activin receptor and functional characterization in Xenopus embryos. Science 1992; 255: 1702–1705.

    Article  PubMed  CAS  Google Scholar 

  78. Tsuchida K, Lewis KA, Mathews LS, Vale WW. Molecular characterization of rat transforming growth factor-beta type II receptor. Biochem Biophys Res Comm 1993; 191: 790–795.

    Article  PubMed  CAS  Google Scholar 

  79. Attisano L, Carcamo J, Ventura F, Weis FM, Massague J, Wrana JL. Identification of human activin and TGF beta type I receptors that form heteromeric kinase complexes with type II receptors. Cell 1993; 75: 671–680.

    Article  PubMed  CAS  Google Scholar 

  80. Wrana JL, Attisano L, Wieser R, Ventura F, Massague J. Mechanism of activation of the TGF-beta receptor. Nature 1994; 370: 341–347.

    Article  PubMed  CAS  Google Scholar 

  81. Attisano L, Wrana JL. Signal transduction by members of the transforming growth factor-beta super-family. Cytokine Growth Factor Rev 1996; 7: 327–339.

    Article  PubMed  CAS  Google Scholar 

  82. Kawabata M, Imamura T, Inoue H, et al. Intracellular signaling of the TGF-beta superfamily by Smad proteins. Ann N Y Acad Sci 1999; 886: 73–82.

    Article  PubMed  CAS  Google Scholar 

  83. Derynck R, Zhang Y, Feng XH. Smads: transcriptional activators of TGF-beta responses. Cell 1998; 95: 737–740.

    Article  PubMed  CAS  Google Scholar 

  84. Hoodless PA, Haerry T, Abdollah S, et al. MADR1, a MAD-related protein that functions in BMP2 signaling pathways. Cell 1996; 85: 489–500.

    Article  PubMed  CAS  Google Scholar 

  85. Baker JC, Harland RM. A novel mesoderm inducer, Madr2, functions in the activin signal transduction pathway. Genes Dev 1996; 10: 1880–1889.

    Article  PubMed  CAS  Google Scholar 

  86. Lagna G, Hata A, Hemmati-Brivanlou A, Massague J. Partnership between DPC4 and SMAD proteins in TGF-beta signalling pathways. Nature 1996; 383: 832–836.

    Article  PubMed  CAS  Google Scholar 

  87. Macias-Silva M, Abdollah S, Hoodless PA, Pirone R, Attisano L, Wrana JL. MADR2 is a substrate of the TGFbeta receptor and its phosphorylation is required for nuclear accumulation and signaling. Cell 1996; 87: 1215–1224.

    Article  PubMed  CAS  Google Scholar 

  88. Wu RY, Zhang Y, Feng XH, Derynck R. Heteromeric and homomeric interactions correlate with signaling activity and functional cooperativity of Smad3 and Smad4/DPC4. Mol Cell Biol 1997; 17: 2521–2528.

    PubMed  CAS  Google Scholar 

  89. Lebrun JJ, Takabe K, Chen Y, Vale W. Roles of pathway-specific and inhibitory Smads in activin receptor signaling. Mol Endocrinol 1999; 13: 15–23.

    Article  PubMed  CAS  Google Scholar 

  90. Graff JM, Bansal A, Melton DA. Xenopus Mad proteins transduce distinct subsets of signals for the TGF beta superfamily. Cell 1996; 85: 479–487.

    Article  PubMed  CAS  Google Scholar 

  91. Nakao A, Roijer E, Imamura T, et al. Identification of Smad2, a human Mad-related protein in the transforming growth factor beta signaling pathway. J Biol Chem 1997; 272: 2896–28900.

    Article  PubMed  CAS  Google Scholar 

  92. Drummond AE, Le MT, Ethier JF, Dyson M, Findlay JK. Expression and localization of activin receptors, Smads, and beta glycan to the postnatal rat ovary. Endocrinology 2002; 143: 1423–1433.

    CAS  Google Scholar 

  93. Chen X, Rubock MJ, Whitman M. A transcriptional partner for MAD proteins in TGF-beta signalling. Nature 1996; 383: 691–696.

    Article  PubMed  CAS  Google Scholar 

  94. Labbe E, Silvestri C, Hoodless PA, Wrana JL, Attisano L. Smad2 and Smad3 positively and negatively regulate TGF beta-dependent transcription through the forkhead DNA-binding protein FAST2. Mol Cell 1998; 2: 109–120.

    Article  PubMed  CAS  Google Scholar 

  95. Li M, Li J, Hoodless PA, et al. Mothers against decapentaplegic-related protein 2 expression in avian granulosa cells is up-regulated by transforming growth factor beta during ovarian follicular development. Endocrinology 1997; 138: 3659–3665.

    Article  PubMed  CAS  Google Scholar 

  96. Hayashi H, Abdollah S, Qiu Y, et al. The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling. Cell 1997; 89: 1165–1173.

    Article  PubMed  CAS  Google Scholar 

  97. Nakao A, Afrakhte M, Moren A, et al. Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature 1997; 389: 631–635.

    Article  PubMed  CAS  Google Scholar 

  98. DePaolo LV. Inhibins, activins, and follistatins: the saga continues. Proc Soc Exp Biol Med 1997; 214: 328–339.

    PubMed  CAS  Google Scholar 

  99. Lewis KA, Gray PC, Blount AL, et al. Betaglycan binds inhibin and can mediate functional antagonism of activin signalling. Nature 2000; 404: 411–414.

    Article  PubMed  CAS  Google Scholar 

  100. Kawakami S, Fujii Y, Okada Y, Winters SJ. Paracrine regulation of FSH by follistatin in folliculostellate cell-enriched primate pituitary cell cultures. Endocrinology 2002; 143: 2250–2258.

    Article  PubMed  CAS  Google Scholar 

  101. Kaiser UB, Chin WW. Regulation of follistatin messenger ribonucleic acid levels in the rat pituitary. J Clin Invest 1993; 91: 2523–2531.

    Article  PubMed  CAS  Google Scholar 

  102. Burger HG, Robertson DM. Editorial: inhibin in the male—progress at last. Endocrinology 1997; 138: 1361–1362.

    Article  PubMed  CAS  Google Scholar 

  103. McCullagh D. Dual endocrine activity of the testes. Science 1932; 76: 19–20.

    Article  PubMed  CAS  Google Scholar 

  104. Krummen LA, Toppari J, Kim WH, et al. Regulation of testicular inhibin subunit messenger ribonucleic acid levels in vivo: effects of hypophysectomy and selective follicle-stimulating hormone replacement. Endocrinology 1989; 125: 1630–1637.

    Article  PubMed  CAS  Google Scholar 

  105. Feng ZM, Wu AZ, Zhang Z, Chen CL. GATA-1 and GATA-4 transactivate inhibin/activin beta-B-subunit gene transcription in testicular cells. Mol Endocrinol 2000; 14: 1820–1835.

    Article  PubMed  CAS  Google Scholar 

  106. Wallace EM, Groome NP, Riley SC, Parker AC, Wu FC. Effects of chemotherapy-induced testicular damage on inhibin, gonadotropin, and testosterone secretion: a prospective longitudinal study. J Clin Endocrinol Metab 1997; 82: 3111–3115.

    Article  PubMed  CAS  Google Scholar 

  107. Carroll RS, Corrigan AZ, Gharib SD, Vale W, Chin WW. Inhibin, activin, and follistatin: regulation of follicle-stimulating hormone messenger ribonucleic acid levels. Mol Endocrinol 1989; 3: 1969–1976.

    Article  PubMed  CAS  Google Scholar 

  108. Anawalt BD, Bebb RA, Matsumoto AM, et al. Serum inhibin B levels reflect Sertoli cell function in normal men and men with testicular dysfunction. J Clin Endocrinol Metab 1996; 81: 3341–3345.

    Article  PubMed  CAS  Google Scholar 

  109. Ramaswamy S, Marshall GR, McNeilly AS, Plant TM. Dynamics of the follicle-stimulating hormone (FSH)-inhibin B feedback loop and its role in regulating spermatogenesis in the adult male rhesus monkey (Macaca mulatta) as revealed by unilateral orchidectomy. Endocrinology 2000; 141: 18–27.

    Article  PubMed  CAS  Google Scholar 

  110. Ramaswamy S, Marshall GR, McNeilly AS, Plant TM. Evidence that in a physiological setting Sertoli cell number is the major determinant of circulating concentrations of inhibin B in the adult male rhesus monkey (Macaca mulatta). J Androl 1999; 20: 430–434.

    PubMed  CAS  Google Scholar 

  111. Simoni M, Gromoll J, Nieschlag E. The follicle-stimulating hormone receptor: biochemistry, molecular biology, physiology, and pathophysiology. Endocr Rev 1997; 18: 739–773.

    Article  PubMed  CAS  Google Scholar 

  112. Tapanainen JS, Vaskivuo T, Aittomaki K, Huhtaniemi IT. Inactivating FSH receptor mutations and gonadal dysfunction. Mol Cell Endocrinol 1998; 145: 129–135.

    Article  PubMed  CAS  Google Scholar 

  113. Kumar TR, Wang Y, Lu N, Matzuk MM. Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nat Genet 1997; 15: 201–204.

    Article  PubMed  CAS  Google Scholar 

  114. de Winter JP, Themmen AP, Hoogerbrugge JW, Klaij IA, Grootegoed JA, de Jong FH. Activin receptor mRNA expression in rat testicular cell types. Mol Cell Endocrinol 1992; 83: R1–R8.

    Article  PubMed  Google Scholar 

  115. Kaipia A, Parvinen M, Toppari J. Localization of activin receptor (ActR-IIB2) mRNA in the rat seminiferous epithelium. Endocrinology 1993; 132: 477–479.

    Article  PubMed  CAS  Google Scholar 

  116. Krummen LA, Moore A, Woodruff TK, et al. Localization of inhibin and activin binding sites in the testis during development by in situ ligand binding. Biol Reprod 1994; 50: 734–744.

    Article  PubMed  CAS  Google Scholar 

  117. Chong H, Pangas SA, Bernard DJ, et al. Structure and expression of a membrane component of the inhibin receptor system. Endocrinology 2000; 141: 2600–2607.

    Article  PubMed  CAS  Google Scholar 

  118. MacConell LA, Leal AM, Vale WW. The distribution of betaglycan protein and mRNA in rat brain, pituitary, and gonads: implications for a role for betaglycan in inhibin-mediated reproductive functions. Endocrinology 2002; 143: 1066–1075.

    Article  PubMed  CAS  Google Scholar 

  119. Lin T, Calkins JK, Morris PL, Vale W, Bardin CW. Regulation of Leydig cell function in primary culture by inhibin and activin. Endocrinology 1989; 125: 2134–2140.

    Article  PubMed  CAS  Google Scholar 

  120. Hsueh AJ, Dahl KD, Vaughan J, et al. Heterodimers and homodimers of inhibin subunits have different paracrine action in the modulation of luteinizing hormone-stimulated androgen biosynthesis. Proc Natl Acad Sci USA 1987; 84: 5082–5086.

    Article  PubMed  CAS  Google Scholar 

  121. Risbridger GP, Clements J, Robertson DM, et al. Immuno-and bioactive inhibin and inhibin alpha-subunit expression in rat Leydig cell cultures. Mol Cell Endocrinol 1989; 66: 119–122.

    Article  PubMed  CAS  Google Scholar 

  122. Mather JP, Attie KM, Woodruff TK, Rice GC, Phillips DM. Activin stimulates spermatogonial proliferation in germ-Sertoli cell cocultures from immature rat testis. Endocrinology 1990; 127: 3206–3214.

    Article  PubMed  CAS  Google Scholar 

  123. van Dissel-Emiliani FM, Grootenhuis AJ, de Jong FH, de Rooij DG. Inhibin reduces spermatogonial numbers in testes of adult mice and Chinese hamsters. Endocrinology 1989; 125: 1899–1903.

    Google Scholar 

  124. Hakovirta H, Kaipia A, Soder O, Parvinen M. Effects of activin-A, inhibin-A, and transforming growth factor-beta 1 on stage-specific deoxyribonucleic acid synthesis during rat seminiferous epithelial cycle. Endocrinology 1993; 133: 1664–1668.

    Article  PubMed  CAS  Google Scholar 

  125. Kirk SE, Dalkin AC, Yasin M, Haisenleder DJ, Marshall JC. Gonadotropin-releasing hormone pulse frequency regulates expression of pituitary follistatin messenger ribonucleic acid: a mechanism for differential gonadotrope function. Endocrinology 1994; 135: 876–880.

    Article  PubMed  CAS  Google Scholar 

  126. Besecke LM, Guendner MJ, Schneyer AL, Bauer-Dantoin AC, Jameson JL, Weiss J. Gonadotropinreleasing hormone regulates follicle-stimulating hormone-beta gene expression through an activin/follistatin autocrine or paracrine loop. Endocrinology 1996; 137: 3667–3673.

    Article  PubMed  CAS  Google Scholar 

  127. Spratt DI, Finkelstein JS, Butler JP, Badger TM, Crowley WF, Jr. Effects of increasing the frequency of low doses of gonadotropin-releasing hormone (GnRH) on gonadotropin secretion in GnRH-deficient men. J Clin Endocrinol Metab 1987; 64: 1179–1186.

    Article  PubMed  CAS  Google Scholar 

  128. Gross KM, Matsumoto AM, Berger RE, Bremner WJ. Increased frequency of pulsatile luteinizing hormone-releasing hormone administration selectively decreases follicle-stimulating hormone levels in men with idiopathic azoospermia. Fertil Steril 1986; 45: 392–396.

    PubMed  CAS  Google Scholar 

  129. Tsujii T, Ishizaka K, Winters SJ. Effects of pituitary adenylate cyclase-activating polypeptide on gonadotropin secretion and subunit messenger ribonucleic acids in perifused rat pituitary cells. Endocrinology 1994; 135: 826–833.

    Article  PubMed  CAS  Google Scholar 

  130. Kaiser UB, Sabbagh E, Katzenellenbogen RA, Conn PM, Chin WW. A mechanism for the differential regulation of gonadotropin subunit gene expression by gonadotropin-releasing hormone. Proc Natl Acad Sci USA 1995; 92: 12280–12284.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Stephen J. Winters MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alan C. Dalkin MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Louisville, Louisville, KY, USA

    Stephen J. Winters MD (Chief) (Chief)

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Science+Business Media New York

About this chapter

Cite this chapter

Winters, S.J., Dalkin, A.C. (2004). Neuroendocrine Control of Testicular Function. In: Winters, S.J. (eds) Male Hypogonadism. Contemporary Endocrinology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-727-7_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-727-7_1

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-739-6

  • Online ISBN: 978-1-59259-727-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation