Skip to main content
SpringerLink
Log in

Effects of Environmental Endocrine Disruptors and Phytoestrogens on the Kisspeptin System

  • Chapter
  • First Online:
Kisspeptin Signaling in Reproductive Biology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 784))

Abstract

Sex steroid hormones, most notably estradiol, play a pivotal role in the sex-specific organization and function of the kisspeptin system. Endocrine-­disrupting compounds are anthropogenic or naturally occurring compounds that interact with steroid hormone signaling. Thus, these compounds have the potential to disrupt the sexually dimorphic ontogeny and function of kisspeptin signaling pathways, resulting in adverse effects on neuroendocrine physiology. This chapter reviews the small but growing body of evidence for endocrine disruption of the kisspeptin system by the exogenous estrogenic compounds bisphenol A, polychlorinated biphenyl mixtures, and the phytoestrogen genistein. Disruption is region, sex, and compound specific, and associated with shifts in the timing of pubertal onset, irregular estrous cycles, and altered sociosexual behavior. These effects highlight that disruption of kisspeptin signaling pathways could have wide ranging effects across multiple organ systems, and potentially underlies a suite of adverse human health trends including precocious female puberty, idiopathic infertility, and metabolic syndrome.

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 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

References

  1. Herman-Giddens ME, Slora EJ, Wasserman RC, Bourdony CJ, Bhapkar MV, Koch GG et al (1997) Secondary sexual characteristics and menses in young girls seen in office practice: a study from the pediatric research in office settings network. Pediatrics 99(4):505–512

    Article  PubMed  CAS  Google Scholar 

  2. Partsch CJ, Sippell WG (2001) Pathogenesis and epidemiology of precocious puberty. Effects of exogenous oestrogens. Hum Reprod Update 7(3):292–302

    Article  PubMed  CAS  Google Scholar 

  3. Aksglaede L, Sorensen K, Petersen JH, Skakkebaek NE, Juul A (2009) Recent decline in age at breast development: the Copenhagen Puberty Study. Pediatrics 123(5):e932–e939

    Article  PubMed  Google Scholar 

  4. Proos LA, Hofvander Y, Tuvemo T (1991) Menarcheal age and growth pattern of Indian girls adopted in Sweden. I. Menarcheal age. Acta Paediatr Scand 80(8–9):852–858

    Article  PubMed  CAS  Google Scholar 

  5. Parent AS, Teilmann G, Juul A, Skakkebaek NE, Toppari J, Bourguignon JP (2003) The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration. Endocr Rev 24(5):668–693

    Article  PubMed  Google Scholar 

  6. Shahab M, Mastronardi C, Seminara SB, Crowley WF, Ojeda SR, Plant TM (2005) Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates. Proc Natl Acad Sci U S A 102(6):2129–2134

    Article  PubMed  CAS  Google Scholar 

  7. Brannian J, Hansen K (2006) Assisted reproductive technologies in South Dakota: the first ten years. S D Med 59(7):291–293

    PubMed  Google Scholar 

  8. Nyboe Andersen A, Erb K (2006) Register data on assisted reproductive technology (ART) in Europe including a detailed description of ART in Denmark. Int J Androl 29(1):12–16

    Article  PubMed  Google Scholar 

  9. Frey KA, Patel KS (2004) Initial evaluation and management of infertility by the primary care physician. Mayo Clin Proc 79(11):1439–43; quiz 43

    Article  PubMed  Google Scholar 

  10. Decherf S, Demeneix BA (2011) The obesogen hypothesis: a shift of focus from the periphery to the hypothalamus. J Toxicol Environ Health B Crit Rev 14(5–7):423–448

    PubMed  CAS  Google Scholar 

  11. Castellano JM, Bentsen AH, Mikkelsen JD, Tena-Sempere M (2010) Kisspeptins: bridging energy homeostasis and reproduction. Brain Res 1364:129–138

    Article  PubMed  CAS  Google Scholar 

  12. Hotchkiss AK, Rider CV, Blystone CR, Wilson VS, Hartig PC, Ankley GT et al (2008) Fifteen years after "Wingspread"—environmental endocrine disrupters and human and wildlife health: where we are today and where we need to go. Toxicol Sci 105(2):235–259

    Article  PubMed  CAS  Google Scholar 

  13. Colborn T, Clement C (1992) Chemically-induced alterations in sexual and functional development: the wildlife/human connection. Princeton Scientific, Princeton, NJ

    Google Scholar 

  14. Toppari J, Larsen JC, Christiansen P, Giwercman A, Grandjean P, Guillette LJ Jr et al (1996) Male reproductive health and environmental xenoestrogens. Environ Health Perspect 104(Suppl 4):741–803

    Article  PubMed  CAS  Google Scholar 

  15. Crisp TM, Clegg ED, Cooper RL, Wood WP, Anderson DG, Baetcke KP et al (1998) Environmental endocrine disruption: an effects assessment and analysis. Environ Health Perspect 106(Suppl 1):11–56

    Article  PubMed  CAS  Google Scholar 

  16. Vandenberg LN, Colborn T, Hayes TB, Heindel JJ, Jacobs DR Jr, Lee DH et al (2012) Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocr Rev 33(3):378–455

    Article  PubMed  CAS  Google Scholar 

  17. Gonzalez FJ, Nebert DW (1990) Evolution of the P450 gene superfamily: animal-plant ‘warfare’, molecular drive and human genetic differences in drug oxidation. Trends Genet 6(6):182–186

    Article  PubMed  CAS  Google Scholar 

  18. Whitten PL, Naftolin F (1991) Dietary plant estrogens: a biologically active background for estrogen action. In: Hochberg RB, Naftolin F (eds) The new biology of steroid hormones. Raven, New York, pp 155–167

    Google Scholar 

  19. Patisaul HB, Jefferson W (2010) The pros and cons of phytoestrogens. Front Neuroendocrinol 31(4):400–419

    Article  PubMed  CAS  Google Scholar 

  20. Leopold A, Erwin M, Oh J, Browning B (1976) Phytoestrogens: adverse effects on reproduction in California quail. Science 191(4222):98–100

    Article  PubMed  CAS  Google Scholar 

  21. Setchell K, Gosselin S, Welsh M, Johnston J, Balisteri W, Kramer L et al (1987) Dietary estrogens-a probable cause of infertility and liver disease in captive cheetahs. Gastroenterology 93:225–233

    PubMed  CAS  Google Scholar 

  22. Adams NR (1995) Detection of the effects of phytoestrogens on sheep and cattle. J Anim Sci 73:1509–1515

    PubMed  CAS  Google Scholar 

  23. Adams NR (1995) Organizational and activational effects of phytoestrogens on the reproductive tract of the ewe. Proc Soc Exp Biol Med 208(1):87–91

    PubMed  CAS  Google Scholar 

  24. Bennetts HW, Underwood EJ, Shier FL (1946) A specific breeding problem of sheep on subterranean clover pastures in Western Australia. Aust Vet J 22:2

    Article  PubMed  CAS  Google Scholar 

  25. Tubbs C, Hartig P, Cardon M, Varga N, Milnes M (2012) Activation of Southern White Rhinoceros (Ceratotherium simum simum) estrogen receptors by phytoestrogens: potential role in the reproductive failure of captive-born females? Endocrinology 153(3):1444–1452

    Article  PubMed  CAS  Google Scholar 

  26. Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT et al (1998) Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 139(10):4252–4263

    Article  PubMed  CAS  Google Scholar 

  27. Dixon RA, Ferreira D (2002) Genistein. Phytochemistry 60(3):205–211

    Article  PubMed  CAS  Google Scholar 

  28. Messina MJ, Persky V, Setchell KD, Barnes S (1994) Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr Cancer 21(2):113–131

    Article  PubMed  CAS  Google Scholar 

  29. Zhang Y, Chen H (2011) Genistein, an epigenome modifier during cancer prevention. Epigenetics 6(7):888–891

    Article  PubMed  Google Scholar 

  30. Gang DR, Kasahara H, Xia ZQ, Van der Mijnsbrugge K, Bauw G, Boerjan W et al (1999) Evolution of plant defense mechanisms. Relationships of phenylcoumaran benzylic ether reductases to pinoresinol-lariciresinol and isoflavone reductases. J Biol Chem 274(11):7516–7527

    Article  PubMed  CAS  Google Scholar 

  31. Bladergroen MR, Spaink HP (1998) Genes and signal molecules involved in the rhizobia-­leguminoseae symbiosis. Curr Opin Plant Biol 1(4):353–359

    Article  PubMed  CAS  Google Scholar 

  32. Kessmann H, Edwards R, Geno PW, Dixon RA (1990) Stress responses in Alfalfa (Medicago sativa L.): V. Constitutive and elicitor-induced accumulation of isoflavonoid conjugates in cell suspension cultures. Plant Physiol 94(1):227–232

    Article  PubMed  CAS  Google Scholar 

  33. D’Aloisio AA, Baird DD, DeRoo LA, Sandler DP (2010) Association of intrauterine and early-life exposures with diagnosis of uterine leiomyomata by 35 years of age in the Sister Study. Environ Health Perspect 118(3):375–381

    Article  PubMed  Google Scholar 

  34. Strom BL, Schinnar R, Ziegler EE, Barnhart KT, Sammel MD, Macones GA et al (2001) Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood. JAMA 286(7):807–814

    Article  PubMed  CAS  Google Scholar 

  35. Frye C, Bo E, Calamandrei G, Calza L, Dessi-Fulgheri F, Fernandez M et al (2012) Endocrine disrupters: a review of some sources, effects, and mechanisms of actions on behavior and neuroendocrine systems. J Neuroendocrinol 24(1):144–159

    Article  PubMed  CAS  Google Scholar 

  36. Swedenborg E, Pongratz I, Gustafsson JA (2010) Endocrine disruptors targeting ERbeta function. Int J Androl 33(2):288–297

    Article  PubMed  CAS  Google Scholar 

  37. Gore AC (2008) Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems. Front Neuroendocrinol 29(3):358–374

    Article  PubMed  CAS  Google Scholar 

  38. Handa RJ, Weiser MJ, Zuloaga DG (2009) A role for the androgen metabolite, ­5alpha-­androstane-3beta,17beta-diol, in modulating oestrogen receptor beta-mediated regulation of hormonal stress reactivity. J Neuroendocrinol 21(4):351–358

    Article  PubMed  CAS  Google Scholar 

  39. Blair RM, Fang H, Branham WS, Hass BS, Dial SL, Moland CL et al (2000) The estrogen receptor relative binding affinities of 188 natural and xenochemicals: structural diversity of ligands. Toxicol Sci 54(1):138–153

    Article  PubMed  CAS  Google Scholar 

  40. Shanle EK, Xu W (2011) Endocrine disrupting chemicals targeting estrogen receptor signaling: identification and mechanisms of action. Chem Res Toxicol 24(1):6–19

    Article  PubMed  CAS  Google Scholar 

  41. Barkhem T, Carlsson B, Nilsson Y, Enmark E, Gustafsson J, Nilsson S (1998) Differential response of estrogen receptor alpha and estrogen receptor beta to partial estrogen agonists/antagonists. Mol Pharmacol 54(1):105–112

    PubMed  CAS  Google Scholar 

  42. Dodds EC, Lawson W (1936) Synthetic estrogenic agents without the phenanthrene nucleus. Nature 137:996

    Article  CAS  Google Scholar 

  43. Vandenberg LN, Hauser R, Marcus M, Olea N, Welshons WV (2007) Human exposure to bisphenol A (BPA). Reprod Toxicol 24(2):139–177

    Article  PubMed  CAS  Google Scholar 

  44. Biedermann S, Tschudin P, Grob K (2010) Transfer of bisphenol A from thermal printer paper to the skin. Anal Bioanal Chem 398(1):571–576

    Article  PubMed  CAS  Google Scholar 

  45. Cooper JE, Kendig EL, Belcher SM (2011) Assessment of bisphenol A released from reusable plastic, aluminium and stainless steel water bottles. Chemosphere 85(6):943–947

    Article  PubMed  CAS  Google Scholar 

  46. Liao C, Kannan K (2011) Widespread occurrence of bisphenol A in paper an. paper products: implications for human exposure. Environ Sci Technol 45(21):9372–9379

    Article  PubMed  CAS  Google Scholar 

  47. Geens T, Goeyens L, Covaci A (2011) Are potential sources for human exposure to bisphenol-­A overlooked? Int J Hyg Environ Health 214(5):339–347

    Article  PubMed  CAS  Google Scholar 

  48. Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL (2008) Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003–2004. Environ Health Perspect 116(1):39–44

    Article  PubMed  CAS  Google Scholar 

  49. vom Saal FS, Akingbemi BT, Belcher SM, Birnbaum LS, Crain DA, Eriksen M et al (2007) Chapel Hill bisphenol A expert panel consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure. Reprod Toxicol 24(2):131–138

    Article  PubMed  CAS  Google Scholar 

  50. Belcher SM, Chen Y, Yan S, Wang HS (2012) Rapid estrogen receptor-mediated mechanisms determine the sexually dimorphic sensitivity of ventricular myocytes to 17beta-estradiol and the environmental endocrine disruptor bisphenol a. Endocrinology 153(2):712–720

    Article  PubMed  CAS  Google Scholar 

  51. Bonefeld-Jorgensen EC, Andersen HR, Rasmussen TH, Vinggaard AM (2001) Effect of highly bioaccumulated polychlorinated biphenyl congeners on estrogen and androgen receptor activity. Toxicology 158(3):141–153

    Article  PubMed  CAS  Google Scholar 

  52. Stein J, Schettler T, Wallinga D, Valenti M (2002) In harm’s way: toxic threats to child development. J Dev Behav Pediatr 23(1 Suppl):S13–S22

    Article  PubMed  Google Scholar 

  53. Adlercreutz H (1995) Phytoestrogens: epidemiology and a possible role in cancer protection. Environ Health Perspect 130(Suppl 7):103–112

    Google Scholar 

  54. UK-Committee-on-Toxicity (2003) Phytoestrogens and health. Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment, London

    Google Scholar 

  55. Setchell KD, Brown NM, Desai P, Zimmer-Nechemias L, Wolfe BE, Brashear WT et al (2001) Bioavailability of pure isoflavones in healthy humans and analysis of commercial soy isoflavone supplements. J Nutr 131(4 Suppl):1362S–1375S

    PubMed  CAS  Google Scholar 

  56. Setchell KDR, Zimmer-Nechemias L, Cai J, Heubi JE (1997) Exposure of infants to phyto-­oestrogens from soy-based infant formula. Lancet 350:23–27

    Article  PubMed  CAS  Google Scholar 

  57. Setchell KD, Zimmer-Nechemias L, Cai J, Heubi JE (1998) Isoflavone content of infant formulas and the metabolic fate of these phytoestrogens in early life. Am J Clin Nutr 68:1453S

    PubMed  CAS  Google Scholar 

  58. Todaka E, Sakurai K, Fukata H, Miyagawa H, Uzuki M, Omori M et al (2005) Fetal exposure to phytoestrogens—the difference in phytoestrogen status between mother and fetus. Environ Res 99(2):195–203

    Article  PubMed  CAS  Google Scholar 

  59. Valentin-Blasini L, Blount BC, Caudill SP, Needham LL (2003) Urinary and serum concentrations of seven phytoestrogens in a human reference population subset. J Expo Anal Environ Epidemiol 13(4):276–282

    Article  PubMed  CAS  Google Scholar 

  60. Adlercreutz H, Fotsis T, Watanabe S, Lampe J, Wahala K, Makela T et al (1994) Determination of lignans and isoflavonoids in plasma by isotope dilution gas chromatography–mass spectrometry. Cancer Detect Prev 18(4):259–271

    PubMed  CAS  Google Scholar 

  61. Padmanabhan V, Siefert K, Ransom S, Johnson T, Pinkerton J, Anderson L et al (2008) Maternal bisphenol-A levels at delivery: a looming problem? J Perinatol 28(4):258–263

    Article  PubMed  CAS  Google Scholar 

  62. Schonfelder G, Wittfoht W, Hopp H, Talsness CE, Paul M, Chahoud I (2002) Parent bisphenol A accumulation in the human maternal-fetal-placental unit. Environ Health Perspect 110(11):A703–A707

    Article  PubMed  Google Scholar 

  63. Peeters PH, Slimani N, van der Schouw YT, Grace PB, Navarro C, Tjonneland A et al (2007) Variations in plasma phytoestrogen concentrations in European adults. J Nutr 137(5):1294–1300

    PubMed  CAS  Google Scholar 

  64. Jacobson JL, Fein GG, Jacobson SW, Schwartz PM, Dowler JK (1984) The transfer of polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs) across the human placenta and into maternal milk. Am J Public Health 74(4):378–379

    Article  PubMed  CAS  Google Scholar 

  65. Longnecker MP, Klebanoff MA, Brock JW, Zhou H (2001) Polychlorinated biphenyl serum levels in pregnant subjects with diabetes. Diabetes Care 24(6):1099–1101

    Article  PubMed  CAS  Google Scholar 

  66. Engel SM, Levy B, Liu Z, Kaplan D, Wolff MS (2006) Xenobiotic phenols in early pregnancy amniotic fluid. Reprod Toxicol 21(1):110–112

    Article  PubMed  CAS  Google Scholar 

  67. Foster WG, Chan S, Platt L, Hughes CL Jr (2002) Detection of phytoestrogens in samples of second trimester human amniotic fluid. Toxicol Lett 129(3):199–205

    Article  PubMed  CAS  Google Scholar 

  68. Nagata C, Iwasa S, Shiraki M, Ueno T, Uchiyama S, Urata K et al (2006) Associations among maternal soy intake, isoflavone levels in urine and blood samples, and maternal and umbilical hormone concentrations (Japan). Cancer Causes Control 17(9):1107–1113

    Article  PubMed  Google Scholar 

  69. Arai Y, Uehara M, Sato Y, Kimira M, Eboshida A, Adlercreutz H et al (2000) Comparison of isoflavones among dietary intake, plasma concentration and urinary excretion for accurate estimation of phytoestrogen intake. J Epidemiol 10:127–135

    Article  PubMed  CAS  Google Scholar 

  70. Ikezuki Y, Tsutsumi O, Takai Y, Kamei Y, Taketani Y (2002) Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure. Hum Reprod 17(11):2839–2841

    Article  PubMed  CAS  Google Scholar 

  71. Adlercreutz H, Yamada T, Wahala K, Watanabe S (1999) Maternal and neonatal phytoestrogens in Japanese women during birth. Am J Obstet Gynecol 180(3 Pt 1):737–743

    Article  PubMed  CAS  Google Scholar 

  72. Ye X, Kuklenyik Z, Needham LL, Calafat AM (2006) Measuring environmental phenols and chlorinated organic chemicals in breast milk using automated on-line column-switching-high performance liquid chromatography-isotope dilution tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 831(1–2):110–115

    PubMed  CAS  Google Scholar 

  73. Franke AA, Custer LJ (1996) Daidzein and genistein concentrations in human milk after soy consumption. Clin Chem 42(6):955–964

    PubMed  CAS  Google Scholar 

  74. Franke AA, Halm BM, Custer LJ, Tatsumura Y, Hebshi S (2006) Isoflavones in breastfed infants after mothers consume soy. Am J Clin Nutr 84(2):406–413

    PubMed  CAS  Google Scholar 

  75. Cao Y, Calafat AM, Doerge DR, Umbach DM, Bernbaum JC, Twaddle NC et al (2009) Isoflavones in urine, saliva, and blood of infants: data from a pilot study on the estrogenic activity of soy formula. J Expo Sci Environ Epidemiol 19(2):223–234

    Article  PubMed  CAS  Google Scholar 

  76. Winter JSD, Hughes IA, Reyes FI, Faiman C (1976) Pituitary-gonadal relations in infancy: patterns of serum gonadal steroid concentrations in man from birth to two years of age. J Clin Endocrinol Metabol 42:679–686

    Article  CAS  Google Scholar 

  77. Farquharson RG, Klopper AI (1984) A study of maternal, retroplacental and umbilical cord estradiol levels in term infants delivered by caesarean section. Eur J Obstet Gynecol Reprod Biol 16(5):315–320

    Article  PubMed  CAS  Google Scholar 

  78. Stricker R, Eberhart R, Chevailler MC, Quinn FA, Bischof P (2006) Establishment of detailed reference values for luteinizing hormone, follicle stimulating hormone, estradiol, and progesterone during different phases of the menstrual cycle on the Abbott ARCHITECT analyzer. Clin Chem Lab Med 44(7):883–887

    Article  PubMed  CAS  Google Scholar 

  79. Kim J, Semaan SJ, Clifton DK, Steiner RA, Dhamija S, Kauffman AS (2011) Regulation of Kiss1 expression by sex steroids in the amygdala of the rat and mouse. Endocrinology 152(5):2020–2030

    Article  PubMed  CAS  Google Scholar 

  80. Wilson C (2011) Neuroendocrinology: Kiss1 expressed in the amygdala in rodents. Nat Rev Endocrinol 7(6):313

    Article  PubMed  Google Scholar 

  81. Terao Y, Kumano S, Takatsu Y, Hattori M, Nishimura A, Ohtaki T et al (2004) Expression of KiSS-1, a metastasis suppressor gene, in trophoblast giant cells of the rat placenta. Biochim Biophys Acta 1678(2–3):102–110

    PubMed  CAS  Google Scholar 

  82. Ohtaki T, Shintani Y, Honda S, Matsumoto H, Hori A, Kanehashi K et al (2001) Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature 411(6837):613–617

    Article  PubMed  CAS  Google Scholar 

  83. Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E et al (2001) The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem 276(37):34631–34636

    Article  PubMed  CAS  Google Scholar 

  84. Castellano JM, Gaytan M, Roa J, Vigo E, Navarro VM, Bellido C et al (2006) Expression of KiSS-1 in rat ovary: putative local regulator of ovulation? Endocrinology 147(10):4852–4862

    Article  PubMed  CAS  Google Scholar 

  85. Clarkson J, Boon WC, Simpson ER, Herbison AE (2009) Postnatal development of an estradiol-­kisspeptin positive feedback mechanism implicated in puberty onset. Endocrinology 150(7):3214–3220

    Article  PubMed  CAS  Google Scholar 

  86. Clarkson J, Herbison AE (2006) Postnatal development of kisspeptin neurons in mouse hypothalamus; sexual dimorphism and projections to gonadotropin-releasing hormone neurons. Endocrinology 147(12):5817–5825

    Article  PubMed  CAS  Google Scholar 

  87. Cao J, Patisaul HB (2011) Sexually dimorphic expression of hypothalamic estrogen receptors alpha and beta and kiss1 in neonatal male and female rats. J Comp Neurol 519(15):2954–2977

    Article  PubMed  CAS  Google Scholar 

  88. Losa SM, Todd KL, Sullivan AW, Cao J, Mickens JA, Patisaul HB (2010) Neonatal exposure to genistein adversely impacts the ontogeny of hypothalamic kisspeptin signaling pathways and ovarian development in the peripubertal female rat. Reprod Toxicol 31(3):280–289

    Article  PubMed  CAS  Google Scholar 

  89. Kauffman AS (2009) Sexual differentiation and the Kiss1 system: hormonal and developmental considerations. Peptides 30(1):83–93

    Article  PubMed  CAS  Google Scholar 

  90. Poling MC, Kauffman AS (2012) Sexually dimorphic testosterone secretion in prenatal and neonatal mice is independent of kisspeptin-Kiss1r and GnRH signaling. Endocrinology 153(2):782–793

    Article  PubMed  CAS  Google Scholar 

  91. Navarro VM, Sanchez-Garrido MA, Castellano JM, Roa J, Garcia-Galiano D, Pineda R et al (2009) Persistent impairment of hypothalamic KiSS-1 system after exposures to estrogenic compounds at critical periods of brain sex differentiation. Endocrinology 150(5):2359–2367

    Article  PubMed  CAS  Google Scholar 

  92. Kauffman AS, Gottsch ML, Roa J, Byquist AC, Crown A, Clifton DK et al (2007) Sexual differentiation of Kiss1 gene expression in the brain of the rat. Endocrinology 148(4):1774–1783

    Article  PubMed  CAS  Google Scholar 

  93. Smith JT, Cunningham MJ, Rissman EF, Clifton DK, Steiner RA (2005) Regulation of Kiss1 gene expression in the brain of the female mouse. Endocrinology 146(9):3686–3692

    Article  PubMed  CAS  Google Scholar 

  94. Smith JT, Popa SM, Clifton DK, Hoffman GE, Steiner RA (2006) Kiss1 neurons in the forebrain as central processors for generating the preovulatory luteinizing hormone surge. J Neurosci 26(25):6687–6694

    Article  PubMed  CAS  Google Scholar 

  95. Patisaul HB, Losa-Ward SM, Todd KL, McCaffrey KA, Mickens JA (2012) Influence of ERbeta selective agonism during the neonatal period on the sexual differentiation of the rat hypothalamic-pituitary-gonadal (HPG) axis. Biol Sex Differ 3(1):2

    Article  PubMed  CAS  Google Scholar 

  96. Patisaul HB, Todd KL, Mickens JA, Adewale HB (2009) Impact of neonatal exposure to the ERalpha agonist PPT, bisphenol-A or phytoestrogens on hypothalamic kisspeptin fiber density in male and female rats. Neurotoxicology 30(3):350–357

    Article  PubMed  CAS  Google Scholar 

  97. Gottsch ML, Navarro VM, Zhao Z, Glidewell-Kenney C, Weiss J, Jameson JL et al (2009) Regulation of Kiss1 and dynorphin gene expression in the murine brain by classical and nonclassical estrogen receptor pathways. J Neurosci 29(29):9390–9395

    Article  PubMed  CAS  Google Scholar 

  98. Gorski RA, Mennin SP, Kubo K (1975) The neural and hormonal bases of the reproductive cycle of the rat. Adv Exp Med Biol 54:115–153

    Article  PubMed  CAS  Google Scholar 

  99. Elkind-Hirsch K, King JC, Gerall AA, Arimura AA (1981) The luteinizing hormone-­releasing hormone (LHRH) system in normal and estrogenized neonatal rats. Brain Res Bull 7(6):645–654

    Article  PubMed  CAS  Google Scholar 

  100. Howdeshell KL, Hotchkiss AK, Thayer KA, Vandenbergh JG, vom Saal FS (1999) Exposure to bisphenol A advances puberty. Nature 401(6755):763–764

    Article  PubMed  CAS  Google Scholar 

  101. Adewale HB, Jefferson WN, Newbold RR, Patisaul HB (2009) Neonatal bisphenol-A exposure alters rat reproductive development and ovarian morphology without impairing activation of gonadotropin releasing hormone neurons. Biol Reprod 81(4):690–699

    Article  PubMed  CAS  Google Scholar 

  102. Birke LI (1984) Effects of estradiol and progesterone on scent-marking behavior of female rats. Horm Behav 18(1):95–98

    Article  PubMed  CAS  Google Scholar 

  103. Cao J, Mickens JA, McCaffrey KA, Leyrer SM, Patisaul HB (2012) Neonatal bisphenol A exposure alters sexually dimorphic gene expression in the postnatal rat hypothalamus. Neurotoxicology 33(1):23–36

    Article  PubMed  CAS  Google Scholar 

  104. Bai Y, Chang F, Zhou R, Jin PP, Matsumoto H, Sokabe M et al (2011) Increase of anteroventral periventricular kisspeptin neurons and generation of E2-induced LH-surge system in male rats exposed perinatally to environmental dose of bisphenol-A. Endocrinology 152(4):1562–1571

    Article  PubMed  CAS  Google Scholar 

  105. Cortes R, Ceccatelli S, Schalling M, Hokfelt T (1990) Differential effects of intracerebroventricular colchicine administration on the expression of mRNAs for neuropeptides and neurotransmitter enzymes, with special emphasis on galanin: an in situ hybridization study. Synapse 6(4):369–391

    Article  PubMed  CAS  Google Scholar 

  106. Plant TM, Ramaswamy S (2009) Kisspeptin and the regulation of the hypothalamic-­pituitary-gonadal axis in the rhesus monkey (Macaca mulatta). Peptides 30(1):67–75

    Article  PubMed  CAS  Google Scholar 

  107. Lackmann GM (2002) Polychlorinated biphenyls and hexachlorobenzene in full-term neonates. Reference values updated. Biol Neonate 81:82–85

    Article  PubMed  CAS  Google Scholar 

  108. Lackmann GM, Schaller KH, Angerer J (2004) Organochlorine compounds in breast-fed vs. bottle-fed infants: preliminary results at six weeks of age. Sci Total Environ 329(1–3):289–293

    Article  PubMed  CAS  Google Scholar 

  109. Bentzen TW, Muir DC, Amstrup SC, O’Hara TM (2008) Organohalogen concentrations in blood and adipose tissue of Southern Beaufort Sea polar bears. Sci Total Environ 406(1–2):352–367

    Article  PubMed  CAS  Google Scholar 

  110. Gladen BC, Doucet J, Hansen LG (2003) Assessing human polychlorinated biphenyl contamination for epidemiologic studies: lessons from patterns of congener concentrations in Canadians in 1992. Environ Health Perspect 111(4):437–443

    Article  PubMed  CAS  Google Scholar 

  111. Dickerson SM, Cunningham SL, Gore AC (2011) Prenatal PCBs disrupt early neuroendocrine development of the rat hypothalamus. Toxicol Appl Pharmacol 252(1):36–46

    Article  PubMed  CAS  Google Scholar 

  112. Dickerson SM, Cunningham SL, Patisaul HB, Woller MJ, Gore AC (2011) Endocrine disruption of brain sexual differentiation by developmental PCB exposure. Endocrinology 152(2):581–594

    Article  PubMed  CAS  Google Scholar 

  113. Steinberg RM, Walker DM, Juenger TE, Woller MJ, Gore AC (2008) Effects of perinatal polychlorinated biphenyls on adult female rat reproduction: development, reproductive physiology, and second generational effects. Biol Reprod 78(6):1091–1101

    Article  PubMed  CAS  Google Scholar 

  114. Steinberg RM, Juenger TE, Gore AC (2007) The effects of prenatal PCBs on adult female paced mating reproductive behaviors in rats. Horm Behav 51(3):364–372

    Article  PubMed  CAS  Google Scholar 

  115. Lanting CI, Huisman M, Muskiet FA, van der Paauw CG, Essed CE, Boersma ER (1998) Polychlorinated biphenyls in adipose tissue, liver, and brain from nine stillborns of varying gestational ages. Pediatr Res 44(2):222–225

    Article  PubMed  CAS  Google Scholar 

  116. Takagi Y, Aburada S, Hashimoto K, Kitaura T (1986) Transfer and distribution of accumulated (14C)polychlorinated biphenyls from maternal to fetal and suckling rats. Arch Environ Contam Toxicol 15(6):709–715

    Article  PubMed  CAS  Google Scholar 

  117. Kriegsfeld LJ, Gibson EM, Williams WP 3rd, Zhao S, Mason AO, Bentley GE et al (2010) The roles of RFamide-related peptide-3 in mammalian reproductive function and behaviour. J Neuroendocrinol 22(7):692–700

    Article  PubMed  CAS  Google Scholar 

  118. Tsutsui K, Bentley GE, Kriegsfeld LJ, Osugi T, Seong JY, Vaudry H (2010) Discovery and evolutionary history of gonadotrophin-inhibitory hormone and kisspeptin: new key neuropeptides controlling reproduction. J Neuroendocrinol 22(7):716–727

    PubMed  CAS  Google Scholar 

  119. Bateman HL, Patisaul HB (2008) Disrupted female reproductive physiology following neonatal exposure to phytoestrogens or estrogen specific ligands is associated with decreased GnRH activation and kisspeptin fiber density in the hypothalamus. Neurotoxicology 29(6):988–997

    Article  PubMed  CAS  Google Scholar 

  120. Setchell KD, Clerici C (2010) Equol: pharmacokinetics and biological actions. J Nutr 140(7):1363S–1368S

    Article  PubMed  CAS  Google Scholar 

  121. Barker DJ (1997) Maternal nutrition, fetal nutrition, and disease in later life. Nutrition 13(9):807–813

    Article  PubMed  CAS  Google Scholar 

  122. Heindel J, Lawler C (2006) Role of exposure to environmental chemicals in developmental origins of health and disease. In: Gluckman P, Hanson M (eds) Developmental origins of health and disease. Cambridge University Press, Cambridge

    Google Scholar 

  123. de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E (2003) Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A 100(19):10972–10976

    Article  PubMed  CAS  Google Scholar 

  124. Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS Jr, Shagoury JK et al (2003) The GPR54 gene as a regulator of puberty. N Engl J Med 349(17):1614–1627

    Article  PubMed  CAS  Google Scholar 

  125. Clarkson J, d’Anglemont de Tassigny X, Moreno AS, Colledge WH, Herbison AE (2008) Kisspeptin-GPR54 signaling is essential for preovulatory gonadotropin-releasing hormone neuron activation and the luteinizing hormone surge. J Neurosci 28(35):8691–8697

    Article  PubMed  CAS  Google Scholar 

  126. Navarro VM, Castellano JM, Fernandez-Fernandez R, Barreiro ML, Roa J, Sanchez-Criado JE et al (2004) Developmental and hormonally regulated messenger ribonucleic acid expression of KiSS-1 and its putative receptor, GPR54, in rat hypothalamus and potent luteinizing hormone-releasing activity of KiSS-1 peptide. Endocrinology 145(10):4565–4574

    Article  PubMed  CAS  Google Scholar 

  127. Messager S, Chatzidaki EE, Ma D, Hendrick AG, Zahn D, Dixon J et al (2005) Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci U S A 102(5):1761–1766

    Article  PubMed  CAS  Google Scholar 

  128. Losa-Ward SM, Todd KL, McCaffrey KA, Tsutsui K, Patisaul HB (2012) Disrupted organization of RFamide pathways in the hypothalamus is associated with advanced puberty in female rats neonatally exposed to bisphenol A. Biol Reprod 87(2):28

    Article  PubMed  CAS  Google Scholar 

  129. Kauffman AS, Navarro VM, Kim J, Clifton D, Steiner RA (2009) Sex differences in the regulation of Kiss1/NKB neurons in juvenile mice: implications for the timing of puberty. Am J Physiol Endocrinol Metab 297(5):E1212–E1221

    Article  PubMed  CAS  Google Scholar 

  130. Ubuka T, Morgan K, Pawson AJ, Osugi T, Chowdhury VS, Minakata H et al (2009) Identification of human GnIH homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic pituitary axis. PLoS One 4(12):e8400

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biology, North Carolina State University, Raleigh, NC, 27695, USA

    Heather B. Patisaul

Authors
  1. Heather B. Patisaul
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Heather B. Patisaul .

Editor information

Editors and Affiliations

  1. , Department of Reproductive Medicine, University of California, San Diego, La Jolla, 92093, California, USA

    Alexander S. Kauffman

  2. School of Anatomy, Physiology and Human Biology, The University of Western Australia, Hackett Drive, Nedlands, 6009, West Australia, Australia

    Jeremy T. Smith

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Patisaul, H.B. (2013). Effects of Environmental Endocrine Disruptors and Phytoestrogens on the Kisspeptin System. In: Kauffman, A., Smith, J. (eds) Kisspeptin Signaling in Reproductive Biology. Advances in Experimental Medicine and Biology, vol 784. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6199-9_21

Download citation

Publish with us

Policies and ethics

Search

Navigation