Journal of Endocrinological Investigation

, Volume 32, Issue 2, pp 175–183 | Cite as

The effect of lead intoxication on endocrine functions

  • K. K. Doumouchtsis
  • S. K. Doumouchtsis
  • E. K. Doumouchtsis
  • D. N. Perrea
Review Article


Studies on the effects of lead on the endocrine system are mainly based on occupationally lead-exposed workers and experimental animal models. Although evidence is conflicting, it has been reported that accumulation of lead affects the majority of the endocrine glands. In particular, it appears to have an effect on the hypothalamic-pituitary axis causing blunted TSH, GH, and FSH/LH responses to TRH, GHRH, and GnRH stimulation, respectively. Suppressed GH release has been reported, probably caused by reduced synthesis of GHRH, inhibition of GHRH release or reduced somatotrope responsiveness. Higher levels of PRL in lead intoxication have been reported. In short-term lead-exposed individuals, high LH and FSH levels are usually associated to normal testosterone concentrations, whereas in long-term exposed individuals’ low testosterone levels do not induce high LH and FSH concentrations. These findings suggest that lead initially causes some subclinical testicular damage, followed by hypothalamic or pituitary disturbance when longer periods of exposure take place. Similarly, lead accumulates in granulosa cells of the ovary, causing delays in growth and pubertal development and reduced fertility in females. In the parenchyma of adrenals histological and cytological changes are demonstrated, causing changes in plasma basal and stress-mediated corticosterone concentrations and reduced cytosolic and nuclear glucocorticoid receptor binding. Thyroid hormone kinetics are also affected. Central defect of the thyroid axis or an alteration in T4 metabolism or binding to proteins may be involved in derangements in thyroid hormone action. Lead toxicity involves alterations on calcitropic hormones’ homeostasis, which increase the risk of skeletal disorders.


Endocrine functions hormone lead intoxication occupational exposure reproductive effects 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Bergdahl IA, Strömberg U, Gerhardsson L, Schütz A, Chettle DR, Skerfving S. Lead concentrations in tibial and calcaneal bone in relation to the history of occupational lead exposure. Scand J Work Environ Health 1998, 24: 38–45.PubMedGoogle Scholar
  2. 2.
    Börjesson J, Gerhardsson L, Schütz A, Mattsson S, Skerfving S, Osterberg K. In vivo measurements of lead in fingerbone in active and retired lead smelters. Int Arch Occup Environ Health 1997, 69: 97–105.PubMedGoogle Scholar
  3. 3.
    Börjesson J, Mattsson S, Strömberg U, Gerhardsson L, Schütz A, Skerfving S. Lead in fingerbone: a tool for retrospective exposure assessment. Arch Environ Health 1997, 52: 104–12.PubMedGoogle Scholar
  4. 4.
    Huseman CA, Varma MM, Angle CR. Neuroendocrine effects of toxic and low blood lead levels in children. Pediatrics 1992, 90: 186–9.PubMedGoogle Scholar
  5. 5.
    Gustafson A, Hedner P, Schütz A, Skerfving S. Occupational lead exposure and pituitary function. Int Arch Occup Environ Health 1989, 61: 277–81.PubMedGoogle Scholar
  6. 6.
    Tuppurainen M, Wägar G, Kurppa K, et al. Thyroid function as assessed by routine laboratory tests of workers with long-term lead exposure. Scand J Work Environ Health 1988, 14: 175–80.PubMedGoogle Scholar
  7. 7.
    Assennato G, Paci C, Baser ME, et al. Sperm count suppression without endocrine dysfunction in lead-exposed men. Arch Environ Health 1987, 42: 124–7.PubMedGoogle Scholar
  8. 8.
    Alexander BH, Checkoway H, van Netten C, et al. Semen quality of men employed at a lead smelter. Occup Environ Med 1996, 53: 411–6.PubMedCentralPubMedGoogle Scholar
  9. 9.
    Lancranjan I, Popescu HI, Gavanescu O, Klepsch I, Serbanescu M. Reproductive ability of workmen occupationally exposed to lead. Arch Environ Health 1975, 30: 396–401.PubMedGoogle Scholar
  10. 10.
    Lerda D. Study of sperm characteristics in persons occupationally exposed to lead. Am J Ind Med 1992, 22: 567–71.PubMedGoogle Scholar
  11. 11.
    Zacharewski T. Identification and assessment of endocrine disruptors: limitations of in vivo and in vitro assays. Environ Health Perspect 1998, 106(Suppl 2): 577–82.PubMedCentralPubMedGoogle Scholar
  12. 12.
    Govoni S, Lucchi L, Battaini F, Spano PF, Trabucchi M. Chronic lead treatment affects dopaminergic control of prolactin secretion in rat pituitary. Toxicol Lett 1984, 20: 237–41.PubMedGoogle Scholar
  13. 13.
    March GL, John TM, McKeown BA, Seleo L, George JC. The effects of lead poisoning on various plasma constituents in the Canada goose. J Wildl Dis 1976, 12: 14–9.PubMedGoogle Scholar
  14. 14.
    Govoni S, Lucchi L, Missale C, Memo M, Spano PF, Trabucchi M. Effect of lead exposure on dopaminergic receptors in rat striatum and nucleus accumbens. Brain Res 1986, 381: 138–42.PubMedGoogle Scholar
  15. 15.
    Govoni S, Battaini F, Fernicola C, Castelletti L, Trabucchi M. Plasma prolactin concentrations in lead exposed workers. J Environ Pathol Toxicol Oncol 1987, 7: 13–5.PubMedGoogle Scholar
  16. 16.
    Fernicola C, Govoni S, Coniglio L, Trabucchi M. Toxicologic hazards at the endocrine level of heavy metals. G Ital Med Lav 1985, 7: 175–80.PubMedGoogle Scholar
  17. 17.
    Alinovi R, Scotti E, Andreoli R, et al. Neuroendocrine and renal effects of inorganic lead. G Ital Med Lav Ergon 2005, 27Suppl 1: 33–8.PubMedGoogle Scholar
  18. 18.
    Pounds JG, Long GJ, Rosen JF. Cellular and molecular toxicity of lead in bone. Environ Health Perspect 1991, 91: 17–32.PubMedCentralPubMedGoogle Scholar
  19. 19.
    Padron VA, Berry WD, Moriarty CM, Anderson TM, Lau YS. Pre- and postnatal effects of lead on hypothalamic GRF levels in rats (abstract) FASEB J 1995, 9: A548.Google Scholar
  20. 20.
    Lau YS, Camoratto AM, White LM, Moriarty CM. Effect of lead on TRH and GRF binding in rat anterior pituitary membranes. Toxicology 1991, 68: 169–79.PubMedGoogle Scholar
  21. 21.
    Huseman CA, Moriarty CM, Angle CR. Childhood lead toxicity and impaired release of thyrotropin-stimulating hormone. Environ Res 1987, 42: 524–33.PubMedGoogle Scholar
  22. 22.
    Ronis MJ, Badger TM, Shema SJ, et al. Endocrine mechanisms underlying the growth effects of developmental lead exposure in the rat. J Toxicol Environ Health A 1998, 54: 101–20.PubMedGoogle Scholar
  23. 23.
    Berry WD Jr, Moriarty CM, Lau YS. Lead attenuation of episodic growth hormone secretion in male rats. Int J Toxicol 2002, 21: 93–8.PubMedGoogle Scholar
  24. 24.
    Camoratto AM, White LM, Lau YS, Ware GO, Berry WD, Moriarty CM. Effect of exposure to low level lead on growth and growth hormone release in rats. Toxicology 1993, 83: 101–14.PubMedGoogle Scholar
  25. 25.
    Dundar B, Oktem F, Arslan MK, et al. The effect of long-term low-dose lead exposure on thyroid function in adolescents. Environ Res 2006, 101: 140–5.PubMedGoogle Scholar
  26. 26.
    Robins JM, Cullen MR, Connors BB, Kayne RD. Depressed thyroid indexes associated with occupational exposure to inorganic lead. Arch Intern Med 1983, 143: 220–4.PubMedGoogle Scholar
  27. 27.
    Singh B, Chandran V, Bandhu HK, et al. Impact of lead exposure on pituitary-thyroid axis in humans. Biometals 2000, 13: 187–92.PubMedGoogle Scholar
  28. 28.
    López CM, Piñeiro AE, Núñez N, Avagnina AM, Villaamil EC, Roses OE. Thyroid hormone changes in males exposed to lead in the Buenos Aires area (Argentina). Pharmacol Res 2000, 42: 599–602.PubMedGoogle Scholar
  29. 29.
    Chaurasia SS, Kar A. Lead induced oxidative damage to the membrane associated type-I iodothyronine-monodeiodinase activity in chicken liver homogenate. Fresenius Environmental Bulletin 1998, 7: 209–215.Google Scholar
  30. 30.
    Swarup D, Naresh R, Varshney VP, et al. Changes in plasma hormones profile and liver function in cows naturally exposed to lead and cadmium around different industrial areas. Res Vet Sci 2007, 82: 16–21.PubMedGoogle Scholar
  31. 31.
    Chaurasia SS, Kar A. Influence of lead on type-I iodothyronine 5′- monodeiodinase activity in male mouse. Horm Metab Res 1997, 29: 532–3.PubMedGoogle Scholar
  32. 32.
    Vyskocil A, Fiala Z, Ettlerová E, Tenjnorová I. Influence of chronic lead exposure on hormone levels in developing rats. J Appl Toxicol 1990, 10: 301–2.PubMedGoogle Scholar
  33. 33.
    Cory-Slechta DA, Virgolini MB, Thiruchelvam M, Weston DD, Bauter MR. Maternal stress modulates the effects of developmental lead exposure. Environ Health Perspect 2004, 112: 717–30.PubMedCentralPubMedGoogle Scholar
  34. 34.
    Nieto-Fernandez FE, Ruiz A, Ntukogu N, Nodimelle L, Pryor SC. Short term lead exposure induces a stress-like response in adult mice. Med Sci Monit 2006, 12: BR325–9.PubMedGoogle Scholar
  35. 35.
    Virgolini MB, Bauter MR, Weston DD, Cory-Slechta DA. Permanent alterations in stress responsivity in female offspring subjected to combined maternal lead exposure and/or stress. Neurotoxicology 2006, 27: 11–21.PubMedGoogle Scholar
  36. 36.
    Baos R, Blas J, Bortolotti GR, Marchant TA, Hiraldo F. Adrenocortical response to stress and thyroid hormone status in free-living nestling white storks (Ciconia ciconia) exposed to heavy metal and arsenic contamination. Environ Halth Perspect 2006, 114: 1497–501.Google Scholar
  37. 37.
    Agrawal R, Chansouria JP. Adrenocortical response to stress in rats exposed to lead nitrate. Res Commun Chem Pathol Pharmacol 1989, 65: 257–60.PubMedGoogle Scholar
  38. 38.
    Kim D, Lawrence DA. Immunotoxic effects of inorganic lead on host resistance of mice with different circling behavior preferences. Brain Behav Immun 2000, 14: 305–17.PubMedGoogle Scholar
  39. 39.
    Cullen MR, Kayne RD, Robins JM. Endocrine and reproductive dysfunction in men associated with occupational inorganic lead intoxication. Arch Environ Health 1984, 39: 431–40.PubMedGoogle Scholar
  40. 40.
    Der R, Yousef M, Fahim Z, Fahim M. Effects of lead and cadmium on adrenal and thyroid functions in rats. Res Commun Chem Pathol Pharmacol 1977, 17: 237–53.PubMedGoogle Scholar
  41. 41.
    Vyskocil A, Fiala Z, Ettlerová E, Tejnorová I. Influence of chronic lead exposure on hormone levels and organ weights in developing rats. Sb Ved Pr Lek Fak Karlovy Univerzity Hradci Kralove 1991, 34: 275–85.PubMedGoogle Scholar
  42. 42.
    Carrasco GA, Van de Kar LD. Neuroendocrine pharmacology of stress. Eur J Pharmacol 2003, 463: 235–72.PubMedGoogle Scholar
  43. 43.
    Van de Kar LD, Blair ML. Forebrain pathways mediating stress-induced hormone secretion. Front Neuroendocrinol 1999, 20: 1–48.PubMedGoogle Scholar
  44. 44.
    Mason HJ, Somervaille LJ, Wright AL, Chettle DR, Scott MC. Effect of occupational lead exposure on serum 1,25-dihydroxyvitamin D levels. Hum Exp Toxicol 1990, 9: 29–34.PubMedGoogle Scholar
  45. 45.
    Kristal-Boneh E, Froom P, Yerushalmi N, Harari G, Ribak J. Calcitropic hormones and occupational lead exposure. Am J Epidemiol 1998, 147: 458–63.PubMedGoogle Scholar
  46. 46.
    Fullmer CS. Dietary calcium levels and treatment interval determine the effects of lead ingestion on plasma 1,25-dihydroxyvitamin D concentration in chicks. J Nutr 1995, 125: 1328–33.PubMedGoogle Scholar
  47. 47.
    Koo WW, Succop PA, Bornschein RL, et al. Serum vitamin D metabolites and bone mineralization in young children with chronic low to moderate lead exposure. Pediatrics 1991, 87: 680–7.PubMedGoogle Scholar
  48. 48.
    Greenberg A, Parkinson DK, Fetterolf DE, et al. Effects of elevated lead and cadmium burdens on renal function and calcium metabolism. Arch Environ Health 1986, 41: 69–76.PubMedGoogle Scholar
  49. 49.
    Smith CM, DeLuca HF, Tanaka Y, Mahaffey KR. Effect of lead ingestion on functions of vitamin D and its metabolites. J Nutr 1981, 111: 1321–9.PubMedGoogle Scholar
  50. 50.
    Edelstein S, Fullmer CS, Wasserman RH. Gastrointestinal absorption of lead in chicks: involvement of the cholecalciferol endocrine system. J Nutr 1984, 114: 692–700.PubMedGoogle Scholar
  51. 51.
    Mahaffey KR, Rosen JF, Chesney RW, Peeler JT, Smith CM, DeLuca HF Association between age, blood lead concentration, and serum 1,25-dihydroxycholecalciferol levels in children. Am J Clin Nutr 1982, 35: 1327–31.PubMedGoogle Scholar
  52. 52.
    Sorrell M, Rosen JF. Interactions of lead, calcium, vitamin D, and nutrition in lead-burdened children. Arch Environ Health 1977, 32: 160–4.PubMedGoogle Scholar
  53. 53.
    Potula V, Henderson A, Kaye W. Calcitropic hormones, bone turnover, and lead exposure among female smelter workers. Arch Environ Occup Health 2005, 60: 195–204.PubMedGoogle Scholar
  54. 54.
    Zuscik MJ, Pateder DB, Puzas JE, Schwarz EM, Rosier RN, O’Keefe RJ. Lead alters parathyroid hormone-related peptide and transforming growth factor-beta 1 effects and AP-1 and NF-kappaB signaling in chondrocytes. J Orthop Res 2002, 20: 811–8.PubMedGoogle Scholar
  55. 55.
    Winder C. The interaction between lead and catecholaminergic function. Biochem Pharmacol 1982, 31: 3717–21.PubMedGoogle Scholar
  56. 56.
    Ng TP, Goh HH, Ng YL, et al. Male endocrine functions in workers with moderate exposure to lead. Br J Ind Med 1991, 48: 485–91.PubMedCentralPubMedGoogle Scholar
  57. 57.
    Telisman S, Colak B, Pizent A, Jurasovic J, Cvitkovic P. Reproductive toxicity of low-level lead exposure in men. Environ Res 2007, 105: 256–66.PubMedGoogle Scholar
  58. 58.
    Vivoli G, Fantuzzi G, Bergomi M, et al. Relationship between low lead exposure and somatic growth in adolescents. J Expo Anal Environ Epidemiol 1993, 3(Suppl 1): 201–9.PubMedGoogle Scholar
  59. 59.
    Angle CR, Kuntzelman DR. Increased erythrocyte protoporphyrins and blood lead—a pilot study of childhood growth patterns. J Toxicol Environ Health 1989, 26: 149–56.PubMedGoogle Scholar
  60. 60.
    Shukla R, et al. Lead exposure and growth in the early preschool child: a follow-up report from the Cincinnati Lead Study. Pediatrics 1991, 88: 886–92.PubMedGoogle Scholar
  61. 61.
    Dearth RK, Hiney JK, Srivastava V, Burdick SB, Bratton GR, Dees WL. Effects of lead (Pb) exposure during gestation and lactation on female pubertal development in the rat. Reprod Toxicol 2002, 16: 343–52.PubMedGoogle Scholar
  62. 62.
    Ronis MJ, Aronson J, Gao GG, et al. Skeletal effects of developmental lead exposure in rats. Toxicol Sci 2001, 62: 321–9.PubMedGoogle Scholar
  63. 63.
    Siegel M, Forsyth B, Siegel L, Cullen MR. The effect of lead on thyroid function in children. Environ Res 1989, 49: 190–6.PubMedGoogle Scholar
  64. 64.
    Gennart JP, Buchet JP, Roels H, Ghyselen P, Ceulemans E, Lauwerys R. Fertility of male workers exposed to cadmium, lead, or manganese. Am J Epidemiol 1992, 135: 1208–19.PubMedGoogle Scholar
  65. 65.
    Refowitz RM. Thyroid function and lead: no clear relationship. J Occup Med 1984, 26: 579–83.PubMedGoogle Scholar
  66. 66.
    Schumacher C, Brodkin CA, Alexander B, et al. Thyroid function in lead smelter workers: absence of subacute or cumulative effects with moderate lead burdens. Int Arch Occup Environ Health 1998, 71: 453–8.PubMedGoogle Scholar
  67. 67.
    Erfurth EM, Gerhardsson L, Nilsson A, et al. Effects of lead on the endocrine system in lead smelter workers. Arch Environ Health 2001, 56: 449–55.PubMedGoogle Scholar
  68. 68.
    Horiguchi S, Endo G, Kiyota I. Measurement of total triiodothyronine (T3), total thyroxine (T4) and thyroid-stimulating hormone (TSH) levels in lead-exposed workers. Osaka City Med J 1987, 33: 51–6.PubMedGoogle Scholar
  69. 69.
    Lockitch G. Perspectives on lead toxicity. Clinical biochemistry 1993, 26: 371–81.PubMedGoogle Scholar
  70. 70.
    Stohs SJ, Bagchi D. Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med 1995, 18: 321–36.PubMedGoogle Scholar
  71. 71.
    Braunstein GD, Dahlgren J, Loriaux DL. Hypogonadism in chronically lead-poisoned men. Infertility 1978, 1: 33–51.PubMedGoogle Scholar
  72. 72.
    Staessen JA, Nawrot T, Hond ED, et al. Renal function, cytogenetic measurements, and sexual development in adolescents in relation to environmental pollutants: a feasibility study of biomarkers. Lancet 2001, 357: 1660–9.PubMedGoogle Scholar
  73. 73.
    Sokol RZ, Madding CE, Swerdloff RS. Lead toxicity and the hypothalamic-pituitary-testicular axis. Biol Reprod 1985, 33: 722–8.PubMedGoogle Scholar
  74. 74.
    Pinon-Lataillade G, Thoreux-Manlay A, Coffigny H, Masse R, Soufir JC. Reproductive toxicity of chronic lead exposure in male and female mice. Hum Exp Toxicol 1995, 14: 872–8.PubMedGoogle Scholar
  75. 75.
    Singh A, Cullen C, Dykeman A, Rice D, Foster W. Chronic lead exposure induces ultrastructural alterations in the monkey testis. J Submicrosc Cytol Pathol 1993, 25: 479–86.PubMedGoogle Scholar
  76. 76.
    Corpas I, Castillo M, Marquina D, Benito MJ. Lead intoxication in gestational and lactation periods alters the development of male reproductive organs. Ecotoxicol Environ Saf 2002, 53: 259–66.PubMedGoogle Scholar
  77. 77.
    Martynowicz H, Andrzejak R, Medras M. [The influence of lead on testis function]. Med Pr 2005, 56: 495–500.PubMedGoogle Scholar
  78. 78.
    Marchlewicz M. [Effectiveness of blood-testis and blood-epididymis barriers for lead]. Ann Acad Med Stetin 1994, 40: 37–51.PubMedGoogle Scholar
  79. 79.
    Wiebe JP, Salhanick AI, Myers KI. On the mechanism of action of lead in the testis: in vitro suppression of FSH receptors, cyclic AMP and steroidogenesis. Life Sci 1983, 32: 1997–2005.PubMedGoogle Scholar
  80. 80.
    Junaid M, Chowdhuri DK, Narayan R, Shanker R, Saxena DK. Lead-induced changes in ovarian follicular development and maturation in mice. J Toxicol Environ Health 1997, 50: 31–40.PubMedGoogle Scholar
  81. 81.
    Vylegzhanina TA, Kuznetsova TE, Maneeva OA, Novikov II, Ryzhkovskaia EL. [Morphofunctional characteristics of the ovaries, thyroid gland and adrenal glands in experimental lead acetate poisoning]. Med Tr Prom Ekol 1993, (9–10): 6–8.PubMedGoogle Scholar
  82. 82.
    Taupeau C, Poupon J, Treton D, Brosse A, Richard Y, Machelon V. Lead reduces messenger RNA and protein levels of cytochrome p450 aromatase and estrogen receptor beta in human ovarian granulosa cells. Biology of reproduction 2003, 68: 1982–8.PubMedGoogle Scholar
  83. 83.
    Hilderbrand DC, Der R, Griffin WT, Fahim MS. Effect of lead acetate on reproduction. American journal of obstetrics and gynecology 1973, 115: 1058–65.PubMedGoogle Scholar
  84. 84.
    Taupeau C, Poupon J, Nomé F, Lefévre B. Lead accumulation in the mouse ovary after treatment-induced follicular atresia. Reprod Toxicol 2001, 15: 385–91.PubMedGoogle Scholar
  85. 85.
    Wiebe JP, Barr KJ, Buckingham KD. Effect of prenatal and neonatal exposure to lead on gonadotropin receptors and steroidogenesis in rat ovaries. J Toxicol Environ Health 1988, 24: 461–76.PubMedGoogle Scholar
  86. 86.
    Nampoothiri LP, Gupta S. Simultaneous effect of lead and cadmium on granulosa cells: a cellular model for ovarian toxicity. Reprod Toxicol 2006, 21: 179–85.PubMedGoogle Scholar
  87. 87.
    Apostoli P, Kiss P, Porru S, Bonde JP, Vanhoorne M. Male reproductive toxicity of lead in animals and humans. ASCLEPIOS Study Group. Occup Environ Med 1998, 55: 364–74.Google Scholar
  88. 88.
    Bonde JP, Joffe M, Apostoli P, et al. Sperm count and chromatin structure in men exposed to inorganic lead: lowest adverse effect levels. Occup Environ Med 2002, 59: 234–42.PubMedCentralPubMedGoogle Scholar
  89. 89.
    Apostoli P, Bellini A, Porru S, Bisanti L. The effect of lead on male fertility: a time to pregnancy (TTP) study. Am J Ind Med 2000, 38: 310–5.PubMedGoogle Scholar
  90. 90.
    Mahmoud A, Kiss P, Vanhoorne M, De Bacquer D, Comhaire F. Is inhibin B involved in the toxic effect of lead on male reproduction? Int J Androl 2005, 28: 150–155PubMedGoogle Scholar
  91. 91.
    Bame JH, Dalton JC, Degelos SD, et al. Effect of long-term immunization against inhibin on sperm output in bulls. Biol Rep 1999, 60: 1360–6.Google Scholar
  92. 92.
    Voglmayr JK, Mizumachi M, Washington DW, Chen CL, Bardin CW. Immunization of rams against human recombinant inhibin alpha-subunit delays, augments, and extends season-related increase in blood gonadotropin levels. Biol Reprod 42: 81–6.Google Scholar
  93. 93.
    Benoff S, Centola GM, Millan C, Napolitano B, Marmar JL, Hurley IR. Increased seminal plasma lead levels adversely affect the fertility potential of sperm in IVF. Hum Rep 2003, 18: 374–83.Google Scholar
  94. 94.
    Benoff S, Hurley IR, Millan C, Napolitano B, Centola GM 2003 Seminal lead concentrations negatively affect outcomes of artificial insemination. Fertil Steril 2003, 80: 517–25.PubMedGoogle Scholar
  95. 95.
    Ronis MJ, Badger TM, Shema SJ, Roberson PK, Shaikh F. Reproductive toxicity and growth effects in rats exposed to lead at different periods during development. Toxicol Appl Pharmacol 1996, 136: 361–71.PubMedGoogle Scholar
  96. 96.
    Sokol RZ, Berman N, Okuda H, Raum W. Effects of lead exposure on GnRH and LH secretion in male rats: response to castration and alpha-methyl-p-tyrosine (AMPT) challenge. Reprod Toxicol 1998, 12: 347–55.PubMedGoogle Scholar
  97. 97.
    Thoreux-Manlay A, Vélez de la Calle JF, Olivier MF, Soufir JC, Masse R, Pinon-Lataillade G. Impairment of testicular endocrine function after lead intoxication in the adult rat. Toxicology 1995, 100: 101–9.PubMedGoogle Scholar
  98. 98.
    McGregor AJ, Mason HJ. Chronic occupational lead exposure and testicular endocrine function. Hum Exp Toxicol 1990, 9: 371–6.PubMedGoogle Scholar
  99. 99.
    Rodamilans M, Osaba MJ, To-Figueras J, et al. Lead toxicity on endocrine testicular function in an occupationally exposed population. Hum Toxicol 1988, 7: 125–8.PubMedGoogle Scholar
  100. 100.
    Pine MD, Hiney JK, Dearth RK, Bratton GR, Dees WL. IGF-1 administration to prepubertal female rats can overcome delayed puberty caused by maternal Pb exposure. Reprod Toxicol 2006, 21: 104–9.PubMedGoogle Scholar
  101. 101.
    Sokol RZ. Reversibility of the toxic effect of lead on the male reproductive axis. Reprod Toxicol 1989, 3: 175–80.PubMedGoogle Scholar
  102. 102.
    Ronis MJ, Gandy J, Badger T. Endocrine mechanisms underlying reproductive toxicity in the developing rat chronically exposed to dietary lead. J Toxicol Environ Health A 1998, 54: 77–99.PubMedGoogle Scholar
  103. 103.
    Kempinas WG, Melo VR, Oliveira-Filho RM, Santos AC, Favaretto AL, Lamano-Carvalho TL. Saturnism in the male rat: endocrine effects. Braz J Med Biol Res 1990, 23: 1171–5.PubMedGoogle Scholar
  104. 104.
    Telisman S, Cvitkovic P, Jurasovic J, Pizent A, Gavella M, Rocic B Semen quality and reproductive endocrine function in relation to biomarkers of lead, cadmium, zinc, and copper in men. Environ Health Perspect 2000, 108: 45–53.PubMedCentralPubMedGoogle Scholar
  105. 105.
    Selevan SG, Rice DC, Hogan KA, Euling SY, Pfahles-Hutchens A, Bethel J. Blood lead concentration and delayed puberty in girls. N Engl J Med 2003, 348: 1527–36.PubMedGoogle Scholar
  106. 106.
    Gorbel F, Boujelbene M, Makni-Ayadi F, et al. [Cytotoxic effects of lead on the endocrine and exocrine sexual function of pubescent male and female rats. Demonstration of apoptotic activity]. C R Biol 2002, 325: 927–40.PubMedGoogle Scholar
  107. 107.
    Wadi SA, Ahmad G. Effects of lead on the male reproductive system in mice. J Toxicol Environ Health A 1999, 56: 513–21.PubMedGoogle Scholar
  108. 108.
    Bruni JF, Marshall S, Dibbet JA, Meites J. Effects of hyper-and hypothyroidism on serum LH and FSH levels in intact and gonadectomized male and female rats. Endocrinology 1975, 97: 558–63.PubMedGoogle Scholar
  109. 109.
    Klein D, Wan YJ, Kamyab S, Okuda H, Sokol RZ. Effects of toxic levels of lead on gene regulation in the male axis: increase in messenger ribonucleic acids and intracellular stores of gonadotrophs within the central nervous system. Biol Reprod 1994, 50: 802–11.PubMedGoogle Scholar
  110. 110.
    Sokol RZ, Wang S, Wan YJ, Stanczyk FZ, Gentzschein E, Chapin RE. Long-term, low-dose lead exposure alters the gonadotropin-releasing hormone system in the male rat. Environ Health Perspect 2002, 110: 871–4.PubMedCentralPubMedGoogle Scholar
  111. 111.
    Bratton GR, Hiney JK, Dees WL. Lead (Pb) alters the norepinephrine-induced secretion of luteinizing hormone releasing hormone from the median eminence of adult male rats in vitro. Life Sci 1994, 55: 563–71.PubMedGoogle Scholar
  112. 112.
    Chang SH, Cheng BH, Lee SL, et al. Low blood lead concentration in association with infertility in women. Environ Res 2006, 101: 380–6.PubMedGoogle Scholar
  113. 113.
    Wu T, Buck GM, Mendola P. Blood lead levels and sexual maturation in U.S. girls: the Third National Health and Nutrition Examination Survey, 1988–1994. Environ Health Perspect 2003, 111: 737–41.PubMedCentralPubMedGoogle Scholar
  114. 114.
    Goyer RA 1990 Transplacental transport of lead. Environ Health Perspect 1990, 89: 101–5.PubMedCentralPubMedGoogle Scholar
  115. 115.
    Borella P, Picco P, Masellis G. Lead content in abortion material from urban women in early pregnancy. Int Arch Occup Environ Health 1986, 57: 93–9.PubMedGoogle Scholar
  116. 116.
    Namihira D, Saldivar L, Pustilnik N, Carreon GJ, Salinas ME. Lead in human blood and milk from nursing women living near a smelter in Mexico City. J Toxicol Environ Health 1993, 38: 225–32.PubMedGoogle Scholar
  117. 117.
    Hiney JK, Ojeda SR, Dees WL. Insulin-like growth factor I: a possible metabolic signal involved in the regulation of female puberty. Neuroendocrinology 1991, 54: 420–3.PubMedGoogle Scholar
  118. 118.
    Barrot M, Marinelli M, Abrous DN, Rougé-Pont F, Le Moal M, Piazza PV. The dopaminergic hyper-responsiveness of the shell of the nucleus accumbens is hormone-dependent. Eur J Neurosci 2000, 12: 973–9.PubMedGoogle Scholar
  119. 119.
    Cory-Slechta DA, McCoy L, Richfield EK. Time course and regional basis of Pb-induced changes in MK-801 binding: reversal by chronic treatment with the dopamine agonist apomorphine but not the D1 agonist SKF-82958. J Neurochem 1997, 68: 2012–23.PubMedGoogle Scholar
  120. 120.
    Peschke E, Kaiser HU, Schrank F, Schumann J. [Morphological studies on the adrenal cortex of Wistar rats following lead poisoning and experimental hypothyroidism]. Gegenbaurs Morphol Jahrb 1981, 127: 869–900.PubMedGoogle Scholar
  121. 121.
    Virgolini MB, Chen K, Weston DD, Bauter MR, Cory-Slechta DA. Interactions of chronic lead exposure and intermittent stress: consequences for brain catecholamine systems and associated behaviors and HPA axis function. Toxicol Sci 2005, 87: 469–82.PubMedGoogle Scholar
  122. 122.
    Wittmers LE Jr, Aufderheide AC, Wallgren J, Rapp G Jr, Alich A. Lead in bone. IV. Distribution of lead in the human skeleton. Arch Environ Health 1988, 43: 381–91.Google Scholar
  123. 123.
    Vega MM, Solórzano JC, Salinas JV. The effects of dietary calcium during lactation on lead in bone mobilization: implications for toxicology. Hum Exp Toxicol 2002, 21: 409–14.PubMedGoogle Scholar
  124. 124.
    Pounds JG. Effect of lead intoxication on calcium homeostasis and calcium-mediated cell function: a review. Neurotoxicology 1984, 5: 295–331.PubMedGoogle Scholar
  125. 125.
    Fullmer CS. Intestinal interactions of lead and calcium. Neurotoxicology 1992, 13: 799–807.PubMedGoogle Scholar
  126. 126.
    Fullmer CS. Intestinal lead and calcium absorption: effect of 1,25-dihydroxycholecalciferol and lead status. Proc Soc Exp Biol Med 1990, 194: 258–64.PubMedGoogle Scholar
  127. 127.
    Dowd TL, Rosen JF, Mints L, Gundberg CM. The effect of Pb(2+) on the structure and hydroxyapatite binding properties of osteocalcin. Biochim Biophys Acta 2001, 1535: 153–63.PubMedGoogle Scholar
  128. 128.
    Rosen JF, Chesney RW, Hamstra A, DeLuca HF, Mahaffey KR. Reduction in 1,25-dihydroxyvitamin D in children with increased lead absorption. New Engl J Med 1980, 302: 1128–31.PubMedGoogle Scholar
  129. 129.
    Kim R, Rotnitsky A, Sparrow D, Weiss S, Wager C, Hu H. A longitudinal study of low-level lead exposure and impairment of renal function. The Normative Aging Study. JAMA 1996, 275: 1177–81.PubMedGoogle Scholar
  130. 130.
    Nash D, Magder LS, Sherwin R, Rubin RJ, Silbergeld EK. Bone density-related predictors of blood lead level among peri- and post-menopausal women in the United States: The Third National Health and Nutrition Examination Survey, 1988–1994. Am J Epidemiol 2004, 160: 901–11.PubMedGoogle Scholar
  131. 131.
    Osman K, Zejda JE, Schütz A, Mielzynska D, Elinder CG, Vahter M Exposure to lead and other metals in children from Katowice district, Poland. Int Arch Occup Environ Health 1998, 71: 180–6.PubMedGoogle Scholar
  132. 132.
    Osterode W, Reining G, Männer G, Jäger J, Vierhapper H. Increased lead excretion correlates with desoxypyridinoline crosslinks in hyperthyroid patients. Thyroid 2000, 10: 161–4.PubMedGoogle Scholar
  133. 133.
    Silbergeld EK, Schwartz J, Mahaffey K. Lead and osteoporosis: mobilization of lead from bone in postmenopausal women. Environ Res 1988, 47: 79–94.PubMedGoogle Scholar
  134. 134.
    Symanski E, Hertz-Picciotto I. Blood lead levels in relation to menopause, smoking, and pregnancy history. Am J Epidemiol 1995, 141: 1047–58.PubMedGoogle Scholar
  135. 135.
    Muldoon SB, Cauley JA, Kuller LH, Scott J, Rohay J. Lifestyle and sociodemographic factors as determinants of blood lead levels in elderly women. Am J Epidemiol 1994, 139: 599–608.PubMedGoogle Scholar
  136. 136.
    Grandjean P, Nielsen GD, Jorgensen PJ, Hørder M 1992 Reference intervals for trace elements in blood: significance of risk factors. Scand J Clin Lab Invest 52: 321–37.PubMedGoogle Scholar
  137. 137.
    Hamilton JD, O’Flaherty EJ 1995 Influence of lead on mineralization during bone growth. Fundam Appl Toxicol 26: 265–71.PubMedGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2009

Authors and Affiliations

  • K. K. Doumouchtsis
    • 1
  • S. K. Doumouchtsis
    • 2
  • E. K. Doumouchtsis
    • 3
  • D. N. Perrea
    • 2
  1. 1.Department of General Medicine and Endocrinology, St George’s HospitalUniversity of LondonLondonUK
  2. 2.Department of Obstetrics and Gynaecology, St George’s HospitalUniversity of LondonLondonUK
  3. 3.Laboratory for Experimental Surgery and Surgical ResearchAthens UniversityAthensGreece

Personalised recommendations