Skip to main content
SpringerLink
Log in

Perchlorate Exposure Induces Hypothyroidism and Affects Thyroid-Responsive Genes in Liver But Not Brain of Quail Chicks

  • Published:
Archives of Environmental Contamination and Toxicology Aims and scope Submit manuscript

Abstract

Ground-dwelling birds in perchlorate-contaminated areas are exposed to perchlorate ion, a known thyroid disruptor, and might be vulnerable to the developmental effects of perchlorate-induced hypothyroidism. We hypothesized that perchlorate-induced hypothyroidism would alter the expression of thyroid-responsive genes involved in thyroid hormone (TH) regulation and in the development of target organ function. Japanese quail chicks were exposed to 2000 mg/L ammonium perchlorate in drinking water for 7.5 weeks beginning on day 5 posthatch. Hypothyroidism was evident after 2 weeks of exposure as lower plasma THs and lower TH content in exposed chicks than in controls. The degree of hypothyroidism was increased at 7.5 weeks, as indicated by significant thyroid gland hypertrophy and sustained changes in thyroid function. After 2 weeks of exposure, hypothyroidism increased type 2 5′-deiodinase (D2) mRNA level and decreased Spot 14 (SP14) mRNA level in the liver, whereas D2 mRNA and RC3 mRNA levels in brain were not affected. After 7.5 weeks of exposure, mRNA levels in the exposed group did not differ from those in controls in either the liver or brain, suggesting the responsiveness of these genes to THs decreased during development. These results suggest that the brain, but not the liver, was protected from the effects of hypothyroidism, probably by changes in D2 activity at the protein level and/or regulation of TH entry and exit from the brain. We concluded that perchlorate exposure caused hypothyroidism in young Japanese quail and affected the expression of thyroid-responsive genes during early posthatch development.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Bates JM, St. Germain DL, Galton VA (1999) Expression profiles of the three iodothyronine deiodinases, D1, D2, and D3, in the developing rat. Endocrinology 140:844–851. doi:10.1210/en.140.2.844

    Article  CAS  Google Scholar 

  • Bernal J (2002) Thyroid hormones and brain development. In: Pfaff D, Arnold A, Etgen A, Fahrbach S, Rubin R (eds) Hormones, brain and behavior. Academic Press, Burlington, pp 543–587

    Chapter  Google Scholar 

  • Bianco AC, Salvatore D, Gereben B, Berry MJ, Larsen PR (2002) Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev 23:38–89. doi:10.1210/er.23.1.38

    Article  CAS  Google Scholar 

  • Brown S, Maloney M, Kinlaw W (1997) “Spot 14” protein functions at the pretranslational level in the regulation of hepatic metabolism by TH and glucose. J Biol Chem 272:2163–2166. doi:10.1074/jbc.272.4.2163

    Article  CAS  Google Scholar 

  • Burmeister LA, Pachucki J, St. Germain DL (1997) Thyroid hormones inhibit type 2 iodothyronine deiodinase in the rat cerebral cortex by both pre- and post-translational mechanisms. Endocrinology 138:5231–5237. doi:10.1210/en.138.12.5231

    Article  CAS  Google Scholar 

  • Chen Y, Sible JC, McNabb FMA (2008) Effects of maternal exposure to ammonium perchlorate on thyroid function and the expression of thyroid-responsive genes in Japanese quail embryos. Gen Comp Endocrinol 159:196–207. doi:10.1016/j.ygcen.2008.08.014

    Article  CAS  Google Scholar 

  • Chopra IJ (1991) Nature, sources, and relative biologic significance of circulating THs. In: Braverman LE, Utiger RD (eds) Werner and Ingbar’s the thyroid: a fundamental and clinical text, 6th edn. J. B. Lippincott, Philadelphia, pp 126–143

    Google Scholar 

  • Gereben B, Bartha T, Tu HM, Harney JW, Rudas P, Larsen PR (1999) Cloning and expression of the chicken type 2 iodothyronine 5′-deiodinase. J Biol Chem 274:13,768–13,776. doi:10.1074/jbc.274.20.13768

    Article  CAS  Google Scholar 

  • Gereben B, Kollar A, Harney JW, Larsen PR (2002) The mRNA structure has potent regulatory effects on type 2 iodothyronine deiodinase expression. Mol Endocrinol 16:1667–1679. doi:10.1210/me.16.7.1667

    Article  CAS  Google Scholar 

  • Gereben B, Pachucki J, Kollar A, Liposits Z, Fekete C (2004) Ontogenic redistribution of type 2 deiodinase messenger ribonucleic acid in the brain of chicken. Endocrinology 145:3619–3625. doi:10.1210/en.2004-0229

    Article  CAS  Google Scholar 

  • Gerendasy DD, Sutcliffe JG (1997) RC3/neurogranin, a postsynaptic calpacitin for setting the response threshold to calcium influxes. Mol Neurobiol 15:131–163. doi:10.1007/BF02740632

    Article  CAS  Google Scholar 

  • Hughes TE, McNabb FMA (1986) Avian hepatic T-3 production by two pathways of 5′-monodeiodination: effects of fasting and patterns during development. J Exp Zool 238:393–399. doi:10.1002/jez.1402380312

    Article  CAS  Google Scholar 

  • Ishitobi H, Mori K, Yoshida K, Watanabe C (2007) Effects of perinatal exposure to low-dose cadmium on thyroid hormone-related and sex hormone receptor gene expressions in brain of offspring. Neurotoxicology 28:790–797. doi:10.1016/j.neuro.2007.02.007

    Article  CAS  Google Scholar 

  • Jackson WA, Anderson TA, Canas JE, Snyder SA, Tan K (2006) Environmental fate of perchlorate. In: Kendall RJ, Smith PN (eds) Perchlorate ecotoxicology. SETAC Press, Pensacola, pp 21–45

    Google Scholar 

  • Jump DB, Narayan P, Towle H, Oppenheimer JH (1984) Rapid effects of triiodothyronine on hepatic gene expression. Hybridization analysis of tissue-specific triiodothyronine regulation of mRNAS14. J Biol Chem 259:2789–2797

    CAS  Google Scholar 

  • Jump DB, Thelen AP, Mater MK (2001) Functional interaction between sterol regulatory element-binding protein-1c, nuclear factor Y, and 3,5,3′-triiodothyronine nuclear receptors. J Biol Chem 276:34,419–34,427 doi:10.1074/jbc.M105471200

    Article  CAS  Google Scholar 

  • Kim SW, Harney JW, Larsen PR (1998) Studies of the hormonal regulation of type 2 5′-iodothyronine deiodinase messenger ribonucleic acid in pituitary tumor cells using semiquantitative reverse transcription-polymerase chain reaction. Endocrinology 139:4895–4905. doi:10.1210/en.139.12.4895

    Article  CAS  Google Scholar 

  • LaFave LT, Augustin LB, Mariash CN (2006) S14: insights from knockout mice. Endocrinology 147:4044–4047. doi:10.1210/en.2006-0473

    Article  CAS  Google Scholar 

  • Lein PJ, Yang D, Bachstetter AD, Tilson HA, Harry GJ, Mervis RF, Kodavanti PRS (2007) Ontogenetic alterations in molecular and structural correlates of dendritic growth after developmental exposure to polychlorinated biphenyls. Environ Health Perspect 115:556–558

    Article  CAS  Google Scholar 

  • Mayer KP, Jackson WA, Snyder SA, Smith PN, Anderson TA (2006) State of the science: background, history, and occurrence. In: Kendall RJ, Smith PN (eds) Perchlorate ecotoxicology. SETAC Press, Pensacola, pp 1–21

    Google Scholar 

  • McNabb FMA (2007) The hypothalamic-pituitary-thyroid (HPT) axis in birds and its role in bird development and reproduction. Crit Rev Toxicol 37:163–193. doi:10.1080/10408440601123552

    Article  CAS  Google Scholar 

  • McNabb FMA, Cheng M-F (1985) Thyroid development in ring doves, Streptopelia risoria. Gen Comp Endocrinol 58:243–251. doi:10.1016/0016-6480(85)90340-5

    Article  CAS  Google Scholar 

  • McNabb FMA, Lyons LJ, Hughes TE (1986) Avian hepatic T3 generation by 5′-monodeiodination: characterization of two enzymatic pathways and the effects of goitrogens. Comp Biochem Physiol A 85:249–255. doi:10.1016/0300-9629(86)90247-1

    Article  CAS  Google Scholar 

  • McNabb FMA, Larsen CT, Pooler PS (2004a) Ammonium perchlorate effects on thyroid function and growth in bobwhite quail chicks. Environ Toxicol Chem 23:997–1003. doi:10.1897/03-362

    Article  CAS  Google Scholar 

  • McNabb FMA, Jang DA, Larsen CT (2004b) Does thyroid function in developing birds adapt to sustained ammonium perchlorate exposure? Toxicol Sci 82:106–113. doi:10.1093/toxsci/kfh247

    Article  CAS  Google Scholar 

  • McNabb FMA, Hooper MJ, Smith EE, Scott M, Gentles BA (2006) Perchlorate effects on birds. In: Kendall RJ, Smith PN (eds) Perchlorate ecotoxicology. SETAC Press, Pensacola, FL, pp 99–127

    Google Scholar 

  • Narayan P, Liaw CW, Towle HC (1984) Rapid induction of a specific nuclear mRNA precursor by thyroid hormone. Proc Natl Acad Sci USA 81:4687–4691. doi:10.1073/pnas.81.15.4687

    Article  CAS  Google Scholar 

  • Nguyen TT, Chapa F, DiStefano JJ III (1998) Direct measurement of the contributions of type I and type II 5′-deiodinases to whole body steady state 3,5,3′-triiodothyronine production from thyroxine in the rat. Endocrinology 139:4626–4633. doi:10.1210/en.139.11.4626

    Article  CAS  Google Scholar 

  • Piosik PA, van Groenigen M, Ponne NJ, Bolhuis PA, Baas F (1995) RC3/neurogranin structure and expression in the caprine brain in relation to congenital hypothyroidism. Mol Brain Res 29:119–130. doi:10.1016/0169-328X(94)00237-9

    Article  CAS  Google Scholar 

  • Piosik PA, van Groenigen M, Baas F (1996) Effect of thyroid hormone deficiency on RC3/neurogranin mRNA expression in the prenatal and adult caprine brain. Mol Brain Res 42:227–235. doi:10.1016/S0169-328X(96)00126-X

    Article  CAS  Google Scholar 

  • Rudas P, Ronai Z, Bartha T (2005) Thyroid hormone metabolism in the brain of domestic animals. Domest Anim Endocrinol 29:88–96. doi:10.1016/j.domaniend.2005.02.032

    Article  CAS  Google Scholar 

  • Sible JC, Anderson JA, Lewellyn AL, Maller JL (1997) Zygotic transcription is required to block a maternal program of apoptosis in Xenopus embryos. Dev Biol 189:335–346 doi:10.1006/dbio.1997.8683

    Google Scholar 

  • Silva JE, Larsen PR (1985) Potential of brown adipose tissue Type II thyroxine 5′-deiodinase as a local and systemic source of triiodothyronine in rats. J Clin Invest 76:2296–2305. doi:10.1172/JCI112239

    Article  CAS  Google Scholar 

  • Steinsapir J, Harney J, Larsen PR (1998) Type 2 iodothyronine deiodinase in rat pituitary tumor cells is inactivated in proteasomes. J Clin Invest 102:1895–1899. doi:10.1172/JCI4672

    Article  CAS  Google Scholar 

  • Verhoelst CHJ, Darras VM, Roelens SA, Artykbaeva GM, Van der Geyten S (2004) Type II iodothyronine deiodinase protein in chicken choroid plexus: additional perspectives on T3 supply in the avian brain. J Endocrinol 183:235–241. doi:10.1677/joe.1.05743

    Article  CAS  Google Scholar 

  • Wang X, Carre W, Zhou H, Lamont SJ, Cogburn LA (2004) Duplicated Spot 14 genes in the chicken: characterization and identification of polymorphisms associated with abdominal fat traits. Gene 332:79–88. doi:10.1016/j.gene.2004.02.021

    Article  CAS  Google Scholar 

  • Wilcoxon JS, Nadolski GJ, Samarut J, Chassande O, Redei EE (2007) Behavioral inhibition and impaired spatial learning and memory in hypothyroid mice lacking TH receptor [alpha]. Behav Brain Res 177:109–116. doi:10.1016/j.bbr.2006.10.030

    Article  CAS  Google Scholar 

  • Wilson CM, McNabb FMA (1997) Maternal thyroid hormones in Japanese quail egg and their influence on embryonic development. Gen Comp Endocrinol 107:153–165. doi:10.1006/gcen.1997.6906

    Article  CAS  Google Scholar 

  • Zeold A, Pormuller L, Dentice M, Harney JW, Curcio-Morelli C, Tente SM, Bianco AC, Gereben B (2006) Metabolic instability of type 2 deiodinase is transferable to stable proteins independently of subcellular localization. J Biol Chem 281:31,538–31,543. doi:10.1074/jbc.M604728200

    Article  CAS  Google Scholar 

  • Zoeller RT, Dowling ALS, Vas AA (2000) Developmental exposure to polychlorinated biphenyls exerts thyroid hormone-like effects on the expression of RC3/Neurogranin and myelin basic protein messenger ribonucleic acids in the developing rat brain. Endocrinology 141:181–189. doi:10.1210/en.141.1.181

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The study was supported by the Strategic Environmental Research and Development Program (SERDP), grants from Graduate Research and Development Program (GRDP), grants from Sigma-Xi grants-in-aids, and a Waste Policy Institute (WPI) summer fellowship. We thank Dr. Michael Denbow, Dr. Bradley Klein, and Dr. Ignacio Moore for useful advice during the study. Laila Queral-Kirkpatrick, Catherine Webb, and Eric Weigel participated in animal sampling. Bambi Jarrett helped with animal care and maintenance.

Author information

Authors and Affiliations

  1. Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24061-0406, USA

    Yu Chen, F. M. Anne McNabb & Jill C. Sible

Authors
  1. Yu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. M. Anne McNabb
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jill C. Sible
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F. M. Anne McNabb.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, Y., McNabb, F.M.A. & Sible, J.C. Perchlorate Exposure Induces Hypothyroidism and Affects Thyroid-Responsive Genes in Liver But Not Brain of Quail Chicks. Arch Environ Contam Toxicol 57, 598–607 (2009). https://doi.org/10.1007/s00244-009-9304-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00244-009-9304-0

Keywords

Search

Navigation