Cumulative and antagonistic effects of a mixture of the antiandrogens vinclozolin and iprodione in the pubertal male rat

Toxicological Sciences

Volumn 111, Issue 1, 2009, Pages 179-188

  Blystone, Chad R ^a,b,c   Lambright, Christy S ^b   Cardon, Mary C ^b   Furr, Johnathan ^b   Rider, Cynthia V ^a,b,d   Hartig, Phillip C ^b   Wilson, Vickie S ^b   Gray Jr , Leon E ^b  

^a NORTH CAROLINA STATE UNIVERSITY   (United States)

^b U S ENVIRONMENTAL PROTECTION AGENCY   (United States)

^c NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

^d DUKE UNIVERSITY   (United States)

Author keywords

Androgen receptor; Endocrine disruption; Iprodione; Mixture; Puberty; Testosterone; Vinclozolin

Indexed keywords

ANDROGEN RECEPTOR; ANTIANDROGEN; IPRODIONE; LUTEINIZING HORMONE; PROGESTERONE; STEROID HORMONE; TESTOSTERONE; VINCLOZOLIN;

ADRENAL GLAND; AGE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOASSAY; BODY WEIGHT; CASTRATION; CONTROLLED STUDY; EPIDIDYMIS; EX VIVO STUDY; GENE EXPRESSION; HERSHBERGER ASSAY; KIDNEY MASS; LIVER WEIGHT; LUTEINIZING HORMONE BLOOD LEVEL; MALE; NONHUMAN; ORGAN WEIGHT; PENIS GLANS; PREPUCE; PREPUTIAL SEPARATION; PROGESTERONE BLOOD LEVEL; PROSTATE VENTRAL LOBE; PUBERTY; RAT; RECEPTOR BINDING; REPRODUCTIVE TOXICITY; SEMINAL VESICLE; SPRAGUE DAWLEY RAT; TESTIS; TESTOSTERONE BLOOD LEVEL;

ADRENAL GLANDS; AMINOIMIDAZOLE CARBOXAMIDE; ANDROGEN ANTAGONISTS; ANIMALS; BODY WEIGHT; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG COMBINATIONS; FUNGICIDES, INDUSTRIAL; GENITALIA, MALE; HORMONES; HYDANTOINS; LIVER; MALE; ORGAN SIZE; OXAZOLES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, ANDROGEN; RECEPTORS, ARYL HYDROCARBON; SEXUAL MATURATION; TRANSCRIPTIONAL ACTIVATION;

RATTUS;

EID: 69049102123     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfp137     Document Type: Article

References (30)

1. Berridge, M. V., and Tan, A. S. (1993). Characterization of the cellular reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT): Subcellular localization, substrate dependence, and involvement of mitochondrial electron transport in MTT reduction. Arch. Biochem. Biophys. 303, 474-482.
2. Blystone, C. R., Furr, J., Lambright, C. S., Howdeshell, K. L., Ryan, B. C., Wilson, V. S., Leblanc, G. A., and Gray, L. E., Jr. (2007a). Prochloraz inhibits testosterone production at dosages below those that affect androgen-dependent organ weights or the onset of puberty in the male Sprague Dawley rat. Toxicol. Sci. 97, 65-74.
3. Blystone, C. R., Lambright, C. S., Furr, J., Wilson, V. S., and Gray, L. E., Jr. (2007b). Iprodione delays male rat pubertal development, reduces serum testosterone levels, and decreases ex vivo testicular testosterone production. Toxicol. Lett. 174, 74-81.
4. EPA. (2003). Vinclozolin; notice of filing a pesticide petition to establish a tolerance for a certain pesticide chemical in or on food. Federal Register 68, 14628-14635.
5. Freyberger, A., and Ahr, H. J. (2004). Development and standardization of a simple binding assay for the detection of compounds with affinity for the androgen receptor. Toxicology 195, 113-126.
6. Goldman, J. M., Cooper, R. L., Rehnberg, G. L., Hein, J. F., McElroy, W. K., and Gray, L. E., Jr. (1986). Effects of low subchronic doses of methoxychlor on the rat hypothalamic-pituitary reproductive axis. Toxicol. Appl. Pharmacol. 86, 474-483.
7. Gray, L. E., Jr., Ostby, J. S., and Kelce, W. R. (1994). Developmental effects of an environmental antiandrogen: The fungicide vinclozolin alters sex differentiation of the male rat. Toxicol. Appl. Pharmacol. 129, 46-52.
8. Gray, L. E., Jr., Wolf, C., Lambright, C., Mann, P., Price, M., Cooper, R. L., and Ostby, J. (1999). Administration of potentially antiandrogenic pesticides (procymidone, linuron, iprodione, chlozolinate, p,p′-DDE, and ketoconazole) and toxic substances (dibutyl- and diethylhexyl phthalate, PCB 169, and ethane dimethane sulphonate) during sexual differentiation produces diverse profiles of reproductive malformations in the male rat. Toxicol. Ind. Health 15, 94-118.
9. Greenwood, F. C., Hunter, W. M., and Glover, J. S. (1963). The preparation of I-131-labelled human growth hormone of high specific radioactivity. Biochem. J. 89, 114-123.
10. Hass, U., Scholze, M., Christiansen, S., Dalgaard, M., Vinggaard, A. M., Axelstad, M., Metzdorff, S. B., and Kortenkamp, A. (2007). Combined exposure to anti-androgens exacerbates disruption of sexual differentiation in the rat. Environ. Health Perspect. 115 (Suppl. 1), 122-128.
11. Hosokawa, S., Murakami, M., Ineyama, M., Yamada, T., Yoshitake, A., Yamada, H., and Miyamoto, J. (1993). The affinity of procymidone to androgen receptor in rats and mice. J. Toxicol. Sci. 18, 83-93.
12. Hotchkiss, A. K., Parks-Saldutti, L. G., Ostby, J. S., Lambright, C., Furr, J., Vandenbergh, J. G., and Gray, L. E., Jr. (2004). A mixture of the "antiandrogens" linuron and butyl benzyl phthalate alters sexual differentiation of the male rat in a cumulative fashion. Biol. Reprod. 71, 1852-1861.
13. Howdeshell, K. L., Furr, J., Lambright, C. R., Rider, C. V., Wilson, V. S., and Gray, L. E., Jr. (2007). Cumulative effects of dibutyl phthalate and diethylhexyl phthalate on male rat reproductive tract development: Altered fetal steroid hormones and genes. Toxicol. Sci. 99 (1), 190-202
14. Howdeshell, K. L., Wilson, V. S., Furr, J., Lambright, C. R., Rider, C. V., Blystone, C. R., Hotchkiss, A. K., and Gray, L. E., Jr. (2008).A mixture of five phthalate esters inhibits fetal testicular testosterone production in the sprague-dawley rat in a cumulative, dose-additive manner. Toxicol. Sci. 105, 153-165.
15. Kelce, W. R., Lambright, C. R., Gray, L. E., Jr., and Roberts, K. P. (1997). Vinclozolin and p,p′-DDE alter androgen-dependent gene expression: In vivo confirmation of an androgen receptor-mediated mechanism. Toxicol. Appl. Pharmacol. 142, 192-200.
16. Kelce, W. R., Monosson, E., Gamcsik, M. P., Laws, S. C., and Gray, L. E., Jr. (1994). Environmental hormone disruptors: Evidence that vinclozolin developmental toxicity is mediated by antiandrogenic metabolites. Toxicol. Appl. Pharmacol. 126, 276-285.
17. Kelce, W. R., Stone, C. R., Laws, S. C., Gray, L. E., Kemppainen, J. A., and Wilson, E. M. (1995). Persistent DDT metabolite p,p′-DDE is a potent androgen receptor antagonist. Nature 375, 581-585.
18. Kennel, P. F., Pallen, C. T., and Bars, R. G. (2004). Evaluation of the rodent Hershberger assay using three reference endocrine disrupters (androgen and antiandrogens). Reprod. Toxicol. 18, 63-73.
19. Lambright, C., Ostby, J., Bobseine, K., Wilson, V., Hotchkiss, A. K., Mann, P. C., and Gray, L. E., Jr. (2000). Cellular and molecular mechanisms of action of linuron: An antiandrogenic herbicide that produces reproductive malformations in male rats. Toxicol. Sci. 56, 389-399.
20. Matsuura, I., Saitoh, T., Ashina, M., Wako, Y., Iwata, H., Toyota, N., Ishizuka, Y., Namiki, M., Hoshino, N., and Tsuchitani, M. (2005). Evaluation of a two-generation reproduction toxicity study adding endpoints to detect endocrine disrupting activity using vinclozolin. J. Toxicol. Sci. 30, Spec No., 163-188.
21. Monosson, E., Kelce, W. R., Lambright, C., Ostby, J., and Gray, L. E., Jr. (1999). Peripubertal exposure to the antiandrogenic fungicide, vinclozolin, delays puberty, inhibits the development of androgen-dependent tissues, and alters androgen receptor function in the male rat. Toxicol. Ind. Health 15, 65-79.
22. Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55-63.
23. National Research Council. (2008). Phthalates and Cumulative Risk Assessment: The Task Ahead. The National Academies Press, Washington, DC.
24. Ostby, J., Kelce, W. R., Lambright, C., Wolf, C. J., Mann, P., and Gray, L. E., Jr. (1999). The fungicide procymidone alters sexual differentiation in the male rat by acting as an androgen-receptor antagonist in vivo and in vitro. Toxicol. Ind. Health 15, 80-93.
25. Rider, C. V., Furr, J., Wilson, V. S., and Gray, L. E., Jr. (2008). A mixture of seven antiandrogens induces reproductive malformations in rats. Int. J. Androl. 31, 249-262.
26. Sapone, A., Affatato, A., Canistro, D., Broccoli, M., Trespidi, S., Pozzetti, L., Biagi, G. L., Cantelli-Forti, G., and Paolini, M. (2003). Induction and suppression of cytochrome P450 isoenzymes and generation of oxygen radicals by procymidone in liver, kidney and lung of CD1 mice. Mutat. Res. 527, 67-80.
27. Stoker, T. E., Cooper, R. L., Lambright, C. S., Wilson, V. S., Furr, J., and Gray, L. E. (2005). In vivo and in vitro anti-androgenic effects of DE-71, a commercial polybrominated diphenyl ether (PBDE) mixture. Toxicol. Appl. Pharmacol. 207, 78-88.
28. Wilson, V. S., Bobseine, K., Lambright, C. R., and Gray, L. E., Jr. (2002). A novel cell line, MDA-kb2, that stably expresses an androgen- and glucocorticoid-responsive reporter for the detection of hormone receptor agonists and antagonists. Toxicol. Sci. 66, 69-81.
29. Wilson, V. S., Cardon, M. C., Gray, L. E., Jr., and Hartig, P. C. (2007). Competitive binding comparison of endocrine-disrupting compounds to recombinant androgen receptor from fathead minnow, rainbow trout, and human. Environ. Toxicol. Chem. 26, 1793-1802.
30. Yamasaki, K., Sawaki, M., Ohta, R., Okuda, H., Katayama, S., Yamada, T., Ohta, T., Kosaka, T., and Owens, W. (2003). OECD validation of the Hershberger assay in Japan: Phase 2 dose response of methyltestosterone, vinclozolin, and p,p′-DDE. Environ. Health Perspect. 111, 1912-1919.