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. 2000 Nov;108(11):1085–1090. doi: 10.1289/ehp.001081085

Limb malformations and abnormal sex hormone concentrations in frogs.

S A Sower 1, K L Reed 1, K J Babbitt 1
PMCID: PMC1240167  PMID: 11102301

Abstract

Declines in amphibian populations, and amphibians with gross malformations, have prompted concern regarding the biological status of many anuran species. A survey of bullfrogs, Rana catesbeiana, and green frogs, Rana clamitans, conducted in central and southern New Hampshire showed malformed frogs at 81% of the sites sampled (13 of 16 sites). Brain gonadotropin-releasing hormone (GnRH) and the synthesis of androgens and estradiol, hormones essential to reproductive processes, were measured from limb-malformed and normal (no limb malformation) frogs. Normal frogs had significantly higher concentrations (nearly 3-fold) of in vitro produced androgens and of brain GnRH than malformed frogs. Because most malformations are thought to occur during development, we propose that environmental factors or endocrine-disrupting chemicals that may cause developmental abnormalities also act during early development to ultimately cause abnormally reduced GnRH and androgen production in adult frogs. The consequences of reduced GnRH and androgens on anuran reproductive behavior and population dynamics are unknown but certainly may be profound and warrant further research.

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Selected References

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  1. Blaustein A. R., Hoffman P. D., Hokit D. G., Kiesecker J. M., Walls S. C., Hays J. B. UV repair and resistance to solar UV-B in amphibian eggs: a link to population declines? Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1791–1795. doi: 10.1073/pnas.91.5.1791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Callard G. V., Petro Z., Ryan K. J. Androgen metabolism in the brain and non-neural tissues of the bullfrog Rana catesbeiana. Gen Comp Endocrinol. 1978 Jan;34(1):18–25. doi: 10.1016/0016-6480(78)90239-3. [DOI] [PubMed] [Google Scholar]
  3. Calvin J. L., Slater C. H., Bolduc T. G., Laudano A. P., Sower S. A. Multiple molecular forms of gonadotropin-releasing hormone in the brain of an elasmobranch: evidence for IR-lamprey GnRH. Peptides. 1993 Jul-Aug;14(4):725–729. doi: 10.1016/0196-9781(93)90104-o. [DOI] [PubMed] [Google Scholar]
  4. Carlsen E., Giwercman A., Keiding N., Skakkebaek N. E. Declining semen quality and increasing incidence of testicular cancer: is there a common cause? Environ Health Perspect. 1995 Oct;103 (Suppl 7):137–139. doi: 10.1289/ehp.95103s7137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Clark E. J., Norris D. O., Jones R. E. Interactions of gonadal steroids and pesticides (DDT, DDE) on gonaduct growth in larval tiger salamanders, Ambystoma tigrinum. Gen Comp Endocrinol. 1998 Jan;109(1):94–105. doi: 10.1006/gcen.1997.7013. [DOI] [PubMed] [Google Scholar]
  6. Colborn T., vom Saal F. S., Soto A. M. Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environ Health Perspect. 1993 Oct;101(5):378–384. doi: 10.1289/ehp.93101378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Conlon J. M., Collin F., Chiang Y. C., Sower S. A., Vaudry H. Two molecular forms of gonadotropin-releasing hormone from the brain of the frog, Rana ribibunda: purification, characterization, and distribution. Endocrinology. 1993 May;132(5):2117–2123. doi: 10.1210/endo.132.5.8477660. [DOI] [PubMed] [Google Scholar]
  8. Crowley W. F., Jr, Jameson J. L. Clinical counterpoint: gonadotropin-releasing hormone deficiency: perspectives from clinical investigation. Endocr Rev. 1992 Nov;13(4):635–640. doi: 10.1210/edrv-13-4-635. [DOI] [PubMed] [Google Scholar]
  9. Facemire C. F., Gross T. S., Guillette L. J., Jr Reproductive impairment in the Florida panther: nature or nurture? Environ Health Perspect. 1995 May;103 (Suppl 4):79–86. doi: 10.1289/ehp.103-1519283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fahien C. M., Sower S. A. Relationship between brain gonadotropin-releasing hormone and final reproductive period of the adult male sea lamprey, Petromyzon marinus. Gen Comp Endocrinol. 1990 Dec;80(3):427–437. doi: 10.1016/0016-6480(90)90192-o. [DOI] [PubMed] [Google Scholar]
  11. Fry D. M. Reproductive effects in birds exposed to pesticides and industrial chemicals. Environ Health Perspect. 1995 Oct;103 (Suppl 7):165–171. doi: 10.1289/ehp.95103s7165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Guillette L. J., Jr, Gross T. S., Gross D. A., Rooney A. A., Percival H. F. Gonadal steroidogenesis in vitro from juvenile alligators obtained from contaminated or control lakes. Environ Health Perspect. 1995 May;103 (Suppl 4):31–36. doi: 10.1289/ehp.95103s431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Guillette L. J., Jr, Gross T. S., Masson G. R., Matter J. M., Percival H. F., Woodward A. R. Developmental abnormalities of the gonad and abnormal sex hormone concentrations in juvenile alligators from contaminated and control lakes in Florida. Environ Health Perspect. 1994 Aug;102(8):680–688. doi: 10.1289/ehp.94102680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hayes T. B. Sex determination and primary sex differentiation in amphibians: genetic and developmental mechanisms. J Exp Zool. 1998 Aug 1;281(5):373–399. [PubMed] [Google Scholar]
  15. Hayes T., Chan R., Licht P. Interactions of temperature and steroids on larval growth, development, and metamorphosis in a toad (Bufo boreas). J Exp Zool. 1993 Jul 1;266(3):206–215. doi: 10.1002/jez.1402660306. [DOI] [PubMed] [Google Scholar]
  16. Hsü C. Y., Chiang C. H., Liang H. M. A histochemical study on the development of hydroxysteroid dehydrogenases in tadpole ovaries. Gen Comp Endocrinol. 1977 Jul;32(3):272–278. doi: 10.1016/0016-6480(77)90206-4. [DOI] [PubMed] [Google Scholar]
  17. Hutcheon D. E., Arnold J. D., ten Hove W., Boyle J., 3rd Disposition, metabolism, and toxicity of methyl tertiary butyl ether, an oxygenate for reformulated gasoline. J Toxicol Environ Health. 1996 Apr 5;47(5):453–464. doi: 10.1080/009841096161609. [DOI] [PubMed] [Google Scholar]
  18. Johnson P. T., Lunde K. B., Ritchie E. G., Launer A. E. The effect of trematode infection on amphibian limb development and survivorship. Science. 1999 Apr 30;284(5415):802–804. doi: 10.1126/science.284.5415.802. [DOI] [PubMed] [Google Scholar]
  19. Katti S. R., Sathyanesan A. G. Changes in the hypothalamo-neurohypophysial complex of lead treated teleostean fish Clarias batrachus (L.). Z Mikrosk Anat Forsch. 1986;100(3):347–352. [PubMed] [Google Scholar]
  20. Ko S. K., Kang H. M., Im W. B., Kwon H. B. Testicular cycles in three species of Korean frogs: Rana nigromaculata, Rana rugosa, and Rana dybowskii. Gen Comp Endocrinol. 1998 Sep;111(3):347–358. doi: 10.1006/gcen.1998.7118. [DOI] [PubMed] [Google Scholar]
  21. Ladd A., Tsong Y. Y., Walfield A. M., Thau R. Development of an antifertility vaccine for pets based on active immunization against luteinizing hormone-releasing hormone. Biol Reprod. 1994 Dec;51(6):1076–1083. doi: 10.1095/biolreprod51.6.1076. [DOI] [PubMed] [Google Scholar]
  22. Licht P., Tsai P. S., Sotowska-Brochocka J. The nature and distribution of gonadotropin-releasing hormones in brains and plasma of ranid frogs. Gen Comp Endocrinol. 1994 May;94(2):186–198. doi: 10.1006/gcen.1994.1075. [DOI] [PubMed] [Google Scholar]
  23. Muller C. H. In vitro stimulationof 5 alpha-dihydrotestosterone and testosterone secretion from bullfrog testis by nonmammalian and mammalian gonadotropins. Gen Comp Endocrinol. 1977 Sep;33(1):109–121. doi: 10.1016/0016-6480(77)90133-2. [DOI] [PubMed] [Google Scholar]
  24. Muller C. H. Plasma 5 alpha-dihydrotestosterone and testosterone in the bullfrog, Rana catesbeiana: stimulation by bullfrog LH. Gen Comp Endocrinol. 1977 Sep;33(1):122–132. doi: 10.1016/0016-6480(77)90134-4. [DOI] [PubMed] [Google Scholar]
  25. Ouellet M., Bonin J., Rodrigue J., DesGranges J. L., Lair S. Hindlimb deformities (ectromelia, ectrodactyly) in free-living anurans from agricultural habitats. J Wildl Dis. 1997 Jan;33(1):95–104. doi: 10.7589/0090-3558-33.1.95. [DOI] [PubMed] [Google Scholar]
  26. Sessions S. K., Franssen R. A., Horner V. L. Morphological clues from multilegged frogs: are retinoids to blame? Science. 1999 Apr 30;284(5415):800–802. doi: 10.1126/science.284.5415.800. [DOI] [PubMed] [Google Scholar]
  27. Sessions S. K., Ruth S. B. Explanation for naturally occurring supernumerary limbs in amphibians. J Exp Zool. 1990 Apr;254(1):38–47. doi: 10.1002/jez.1402540107. [DOI] [PubMed] [Google Scholar]
  28. Sower S. A., Schreck C. B. Steroid and thyroid hormones during sexual maturation of coho salmon (Oncorhynchus kisutch) in seawater of fresh water. Gen Comp Endocrinol. 1982 May;47(1):42–53. doi: 10.1016/0016-6480(82)90082-x. [DOI] [PubMed] [Google Scholar]
  29. Stopa E. G., Sower S. A., Svendsen C. N., King J. C. Polygenic expression of gonadotropin-releasing hormone (GnRH) in human? Peptides. 1988 Mar-Apr;9(2):419–423. doi: 10.1016/0196-9781(88)90278-1. [DOI] [PubMed] [Google Scholar]
  30. Van der Kraak G. J., Munkittrick K. R., McMaster M. E., Portt C. B., Chang J. P. Exposure to bleached kraft pulp mill effluent disrupts the pituitary-gonadal axis of white sucker at multiple sites. Toxicol Appl Pharmacol. 1992 Aug;115(2):224–233. doi: 10.1016/0041-008x(92)90327-o. [DOI] [PubMed] [Google Scholar]
  31. Wolff M. S., Toniolo P. G. Environmental organochlorine exposure as a potential etiologic factor in breast cancer. Environ Health Perspect. 1995 Oct;103 (Suppl 7):141–145. doi: 10.1289/ehp.95103s7141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yu K. L., Nahorniak C. S., Peter R. E., Corrigan A., Rivier J. E., Vale W. W. Brain distribution of radioimmunoassayable gonadotropin-releasing hormone in female goldfish: seasonal variation and periovulatory changes. Gen Comp Endocrinol. 1987 Aug;67(2):234–246. doi: 10.1016/0016-6480(87)90153-5. [DOI] [PubMed] [Google Scholar]

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