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. 2003 Aug;111(10):1278–1282. doi: 10.1289/ehp.6126

Effects of polychlorinated biphenyls on estrogen receptor-beta expression in the anteroventral periventricular nucleus.

Jacklyn Salama 1, Tandra R Chakraborty 1, Laurie Ng 1, Andrea C Gore 1
PMCID: PMC1241606  PMID: 12896846

Abstract

Polychlorinated biphenyls (PCBs) can disrupt the reproductive axis, particularly when the exposure occurs during the vulnerable developmental periods. Some effects of environmental endocrine disruptors such as PCBs may be exerted through binding to estrogen receptors (ERs). In this study we examined the endocrine-disrupting effects of Aroclor 1221 (a commercial PCB mixture), focusing on its actions on the ER-ss, which has been implicated in mediating effects of endocrine-disrupting chemicals. A low, ecologically relevant dose of Aroclor 1221 or vehicle (ethanol) was administered three times each to rat dams, on gestational day 16 and on postpartum days 1 and 4, a developmental period during which steroid hormones have permanent effects on adult brain structure and function. Effects on ER-ss cell number in the anteroventral periventricular nucleus (AVPV) were quantified; this sexually dimorphic nucleus of the brain is essential to female reproductive function. For comparison, we quantified ER-ss cell number in another hypothalamic region, the supraoptic nucleus (SON). Using a stereologic approach, we found that Aroclor 1221 caused a highly significant down-regulation of the number of ER-ss-expressing cells in the AVPV, but had no effect in the SON. Thus, PCB exposure has consequences for neural ER expression, and these findings have implications for wildlife and humans that have been exposed to environmental estrogens, particularly during the susceptible periods of early development.

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Selected References

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  1. Alves S. E., Lopez V., McEwen B. S., Weiland N. G. Differential colocalization of estrogen receptor beta (ERbeta) with oxytocin and vasopressin in the paraventricular and supraoptic nuclei of the female rat brain: an immunocytochemical study. Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3281–3286. doi: 10.1073/pnas.95.6.3281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Amico J. A., Davis A. M., McCarthy M. M. An ovarian steroid hormone regimen that increases hypothalamic oxytocin expression alters [3H] muscimol binding in the hypothalamic supraoptic nucleus of the female rat. Brain Res. 2000 Feb 28;857(1-2):279–282. doi: 10.1016/s0006-8993(99)02373-2. [DOI] [PubMed] [Google Scholar]
  3. Atanassova N., McKinnell C., Turner K. J., Walker M., Fisher J. S., Morley M., Millar M. R., Groome N. P., Sharpe R. M. Comparative effects of neonatal exposure of male rats to potent and weak (environmental) estrogens on spermatogenesis at puberty and the relationship to adult testis size and fertility: evidence for stimulatory effects of low estrogen levels. Endocrinology. 2000 Oct;141(10):3898–3907. doi: 10.1210/endo.141.10.7723. [DOI] [PubMed] [Google Scholar]
  4. Brezner E., Terkel J., Perry A. S. The effect of Aroclor 1254 (PCB) on the physiology of reproduction in the female rat--I. Comp Biochem Physiol C. 1984;77(1):65–70. doi: 10.1016/0742-8413(84)90131-2. [DOI] [PubMed] [Google Scholar]
  5. Bush B., Streeter R. W., Sloan R. J. Polychlorobiphenyl (PCB) congeners in striped bass (Morone saxatilis) from marine and estuarine waters of New York State determined by capillary gas chromatography. Arch Environ Contam Toxicol. 1990 Jan-Feb;19(1):49–61. doi: 10.1007/BF01059812. [DOI] [PubMed] [Google Scholar]
  6. Chakraborty Tandra R., Ng Laurie, Gore Andrea C. Colocalization and hormone regulation of estrogen receptor alpha and N-methyl-D-aspartate receptor in the hypothalamus of female rats. Endocrinology. 2003 Jan;144(1):299–305. doi: 10.1210/en.2002-220749. [DOI] [PubMed] [Google Scholar]
  7. Chung Y. W., Clemens L. G. Effects of perinatal exposure to polychlorinated biphenyls on development of female sexual behavior. Bull Environ Contam Toxicol. 1999 Jun;62(6):664–670. doi: 10.1007/s001289900925. [DOI] [PubMed] [Google Scholar]
  8. Connor K., Ramamoorthy K., Moore M., Mustain M., Chen I., Safe S., Zacharewski T., Gillesby B., Joyeux A., Balaguer P. Hydroxylated polychlorinated biphenyls (PCBs) as estrogens and antiestrogens: structure-activity relationships. Toxicol Appl Pharmacol. 1997 Jul;145(1):111–123. doi: 10.1006/taap.1997.8169. [DOI] [PubMed] [Google Scholar]
  9. Cooper R. L., Kavlock R. J. Endocrine disruptors and reproductive development: a weight-of-evidence overview. J Endocrinol. 1997 Feb;152(2):159–166. doi: 10.1677/joe.0.1520159. [DOI] [PubMed] [Google Scholar]
  10. Davis E. C., Shryne J. E., Gorski R. A. Structural sexual dimorphisms in the anteroventral periventricular nucleus of the rat hypothalamus are sensitive to gonadal steroids perinatally, but develop peripubertally. Neuroendocrinology. 1996 Feb;63(2):142–148. doi: 10.1159/000126950. [DOI] [PubMed] [Google Scholar]
  11. Ecobichon D. J., MacKenzie D. O. The uterotropic activity of commercial and isomerically-pure chlorobiphenyls in the rat. Res Commun Chem Pathol Pharmacol. 1974 Sep;9(1):85–95. [PubMed] [Google Scholar]
  12. Evans M. S., Noguchi G. E., Rice C. P. The biomagnification of polychlorinated biphenyls, toxaphene, and DDT compounds in a Lake Michigan offshore food web. Arch Environ Contam Toxicol. 1991 Jan;20(1):87–93. doi: 10.1007/BF01065333. [DOI] [PubMed] [Google Scholar]
  13. Faqi A. S., Dalsenter P. R., Merker H. J., Chahoud I. Effects on developmental landmarks and reproductive capability of 3,3',4,4'-tetrachlorobiphenyl and 3,3',4,4',5-pentachlorobiphenyl in offspring of rats exposed during pregnancy. Hum Exp Toxicol. 1998 Jul;17(7):365–372. doi: 10.1177/096032719801700702. [DOI] [PubMed] [Google Scholar]
  14. Gellert R. J. Uterotrophic activity of polychlorinated biphenyls (PCB) and induction of precocious reproductive aging in neonatally treated female rats. Environ Res. 1978 Jul;16(1-3):123–130. doi: 10.1016/0013-9351(78)90149-4. [DOI] [PubMed] [Google Scholar]
  15. Gore A. C. Environmental toxicant effects on neuroendocrine function. Endocrine. 2001 Mar;14(2):235–246. doi: 10.1385/ENDO:14:2:235. [DOI] [PubMed] [Google Scholar]
  16. Gu G. B., Simerly R. B. Projections of the sexually dimorphic anteroventral periventricular nucleus in the female rat. J Comp Neurol. 1997 Jul 21;384(1):142–164. [PubMed] [Google Scholar]
  17. Hall Julie M., Korach Kenneth S. Analysis of the molecular mechanisms of human estrogen receptors alpha and beta reveals differential specificity in target promoter regulation by xenoestrogens. J Biol Chem. 2002 Aug 27;277(46):44455–44461. doi: 10.1074/jbc.M200849200. [DOI] [PubMed] [Google Scholar]
  18. Hany J., Lilienthal H., Sarasin A., Roth-Härer A., Fastabend A., Dunemann L., Lichtensteiger W., Winneke G. Developmental exposure of rats to a reconstituted PCB mixture or aroclor 1254: effects on organ weights, aromatase activity, sex hormone levels, and sweet preference behavior. Toxicol Appl Pharmacol. 1999 Aug 1;158(3):231–243. doi: 10.1006/taap.1999.8710. [DOI] [PubMed] [Google Scholar]
  19. Higuchi Takashi, Okere Chuma O. Role of the supraoptic nucleus in regulation of parturition and milk ejection revisited. Microsc Res Tech. 2002 Jan 15;56(2):113–121. doi: 10.1002/jemt.10016. [DOI] [PubMed] [Google Scholar]
  20. Hrabovszky E., Kalló I., Hajszán T., Shughrue P. J., Merchenthaler I., Liposits Z. Expression of estrogen receptor-beta messenger ribonucleic acid in oxytocin and vasopressin neurons of the rat supraoptic and paraventricular nuclei. Endocrinology. 1998 May;139(5):2600–2604. doi: 10.1210/endo.139.5.6024. [DOI] [PubMed] [Google Scholar]
  21. Hutton L. A., Gu G., Simerly R. B. Development of a sexually dimorphic projection from the bed nuclei of the stria terminalis to the anteroventral periventricular nucleus in the rat. J Neurosci. 1998 Apr 15;18(8):3003–3013. doi: 10.1523/JNEUROSCI.18-08-03003.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Jansen H. T., Cooke P. S., Porcelli J., Liu T. C., Hansen L. G. Estrogenic and antiestrogenic actions of PCBs in the female rat: in vitro and in vivo studies. Reprod Toxicol. 1993 May-Jun;7(3):237–248. doi: 10.1016/0890-6238(93)90230-5. [DOI] [PubMed] [Google Scholar]
  23. Kester M. H., Bulduk S., Tibboel D., Meinl W., Glatt H., Falany C. N., Coughtrie M. W., Bergman A., Safe S. H., Kuiper G. G. Potent inhibition of estrogen sulfotransferase by hydroxylated PCB metabolites: a novel pathway explaining the estrogenic activity of PCBs. Endocrinology. 2000 May;141(5):1897–1900. doi: 10.1210/endo.141.5.7530. [DOI] [PubMed] [Google Scholar]
  24. Khan I. A., Thomas P. Aroclor 1254-induced alterations in hypothalamic monoamine metabolism in the Atlantic croaker (Micropogonias undulatas): correlation with pituitary gonadotropin release. Neurotoxicology. 1997;18(2):553–560. [PubMed] [Google Scholar]
  25. Kuiper G. G., Lemmen J. G., Carlsson B., Corton J. C., Safe S. H., van der Saag P. T., van der Burg B., Gustafsson J. A. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology. 1998 Oct;139(10):4252–4263. doi: 10.1210/endo.139.10.6216. [DOI] [PubMed] [Google Scholar]
  26. Laessig S. A., McCarthy M. M., Silbergeld E. K. Neurotoxic effects of endocrine disruptors. Curr Opin Neurol. 1999 Dec;12(6):745–751. doi: 10.1097/00019052-199912000-00015. [DOI] [PubMed] [Google Scholar]
  27. Le W. W., Wise P. M., Murphy A. Z., Coolen L. M., Hoffman G. E. Parallel declines in Fos activation of the medial anteroventral periventricular nucleus and LHRH neurons in middle-aged rats. Endocrinology. 2001 Nov;142(11):4976–4982. doi: 10.1210/endo.142.11.8470. [DOI] [PubMed] [Google Scholar]
  28. Lundkvist U. Clinical and reproductive effects of Clophen A50 (PCB) administered during gestation on pregnant guinea pigs and their offspring. Toxicology. 1990 Apr 30;61(3):249–257. doi: 10.1016/0300-483x(90)90175-g. [DOI] [PubMed] [Google Scholar]
  29. Madeira M. D., Sousa N., Cadete-Leite A., Lieberman A. R., Paula-Barbosa M. M. The supraoptic nucleus of the adult rat hypothalamus displays marked sexual dimorphism which is dependent on body weight. Neuroscience. 1993 Feb;52(3):497–513. doi: 10.1016/0306-4522(93)90402-2. [DOI] [PubMed] [Google Scholar]
  30. McEwen B. S., Alves S. E. Estrogen actions in the central nervous system. Endocr Rev. 1999 Jun;20(3):279–307. doi: 10.1210/edrv.20.3.0365. [DOI] [PubMed] [Google Scholar]
  31. Milner T. A., McEwen B. S., Hayashi S., Li C. J., Reagan L. P., Alves S. E. Ultrastructural evidence that hippocampal alpha estrogen receptors are located at extranuclear sites. J Comp Neurol. 2001 Jan 15;429(3):355–371. [PubMed] [Google Scholar]
  32. Newland M. C., Paletz E. M. Animal studies of methylmercury and PCBs: what do they tell us about expected effects in humans? Neurotoxicology. 2000 Dec;21(6):1003–1027. [PubMed] [Google Scholar]
  33. Orikasa Chitose, Kondo Yasuhiko, Hayashi Shinji, McEwen Bruce S., Sakuma Yasuo. Sexually dimorphic expression of estrogen receptor beta in the anteroventral periventricular nucleus of the rat preoptic area: implication in luteinizing hormone surge. Proc Natl Acad Sci U S A. 2002 Feb 19;99(5):3306–3311. doi: 10.1073/pnas.052707299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ramaley J. A. Development of Gonadotropin regulation in the prepubertal mammal. Biol Reprod. 1979 Feb;20(1):1–31. doi: 10.1093/biolreprod/20.1.1. [DOI] [PubMed] [Google Scholar]
  35. Sager D. B. Effect of postnatal exposure to polychlorinated biphenyls on adult male reproductive function. Environ Res. 1983 Jun;31(1):76–94. doi: 10.1016/0013-9351(83)90063-4. [DOI] [PubMed] [Google Scholar]
  36. Schmitz C., Hof P. R. Recommendations for straightforward and rigorous methods of counting neurons based on a computer simulation approach. J Chem Neuroanat. 2000 Oct;20(1):93–114. doi: 10.1016/s0891-0618(00)00066-1. [DOI] [PubMed] [Google Scholar]
  37. Shughrue P. J., Lane M. V., Merchenthaler I. Comparative distribution of estrogen receptor-alpha and -beta mRNA in the rat central nervous system. J Comp Neurol. 1997 Dec 1;388(4):507–525. doi: 10.1002/(sici)1096-9861(19971201)388:4<507::aid-cne1>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  38. Shughrue P. J., Merchenthaler I. Distribution of estrogen receptor beta immunoreactivity in the rat central nervous system. J Comp Neurol. 2001 Jul 16;436(1):64–81. [PubMed] [Google Scholar]
  39. Simerly R. B. Hormonal control of the development and regulation of tyrosine hydroxylase expression within a sexually dimorphic population of dopaminergic cells in the hypothalamus. Brain Res Mol Brain Res. 1989 Dec;6(4):297–310. doi: 10.1016/0169-328x(89)90075-2. [DOI] [PubMed] [Google Scholar]
  40. Simerly R. B., Swanson L. W. The distribution of neurotransmitter-specific cells and fibers in the anteroventral periventricular nucleus: implications for the control of gonadotropin secretion in the rat. Brain Res. 1987 Jan 1;400(1):11–34. doi: 10.1016/0006-8993(87)90649-4. [DOI] [PubMed] [Google Scholar]
  41. Tilson H. A., Kodavanti P. R., Mundy W. R., Bushnell P. J. Neurotoxicity of environmental chemicals and their mechanism of action. Toxicol Lett. 1998 Dec 28;102-103:631–635. doi: 10.1016/s0378-4274(98)00271-9. [DOI] [PubMed] [Google Scholar]
  42. Torner L., Nava G., Dueñas Z., Corbacho A., Mejía S., López F., Cajero M., Martínez de la Escalera G., Clapp C. Changes in the expression of neurohypophyseal prolactins during the estrous cycle and after estrogen treatment. J Endocrinol. 1999 Jun;161(3):423–432. doi: 10.1677/joe.0.1610423. [DOI] [PubMed] [Google Scholar]
  43. Webb R. G., McCall A. C. Identities of polychlorinated biphenyl isomers in aroclors. J Assoc Off Anal Chem. 1972 Jul;55(4):746–752. [PubMed] [Google Scholar]
  44. West M. J., Slomianka L., Gundersen H. J. Unbiased stereological estimation of the total number of neurons in thesubdivisions of the rat hippocampus using the optical fractionator. Anat Rec. 1991 Dec;231(4):482–497. doi: 10.1002/ar.1092310411. [DOI] [PubMed] [Google Scholar]
  45. Wiegand S. J., Terasawa E., Bridson W. E. Persistent estrus and blockade of progesterone-induced LH release follows lesions which do not damage the suprachiasmatic nucleus. Endocrinology. 1978 May;102(5):1645–1648. doi: 10.1210/endo-102-5-1645. [DOI] [PubMed] [Google Scholar]
  46. Wiegand S. J., Terasawa E. Discrete lesions reveal functional heterogeneity of suprachiasmatic structures in regulation of gonadotropin secretion in the female rat. Neuroendocrinology. 1982 Jun;34(6):395–404. doi: 10.1159/000123335. [DOI] [PubMed] [Google Scholar]
  47. Zoeller Thomas R., Dowling Amy L. S., Herzig Carolyn T. A., Iannacone Eric A., Gauger Kelly J., Bansal Ruby. Thyroid hormone, brain development, and the environment. Environ Health Perspect. 2002 Jun;110 (Suppl 3):355–361. doi: 10.1289/ehp.02110s3355. [DOI] [PMC free article] [PubMed] [Google Scholar]

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