Effects of in utero exposure to finasteride on androgen-dependent reproductive development in the male rat

Toxicological Sciences

Volumn 74, Issue 2, 2003, Pages 393-406

  Bowman, Christopher J ^a,d   Barlow, Norman J ^b,d   Turner, Katie J ^c,d   Wallace, Duncan G ^d   Foster, Paul M D ^d  

^a CIIT CENTERS FOR HEALTH RESEARCH   (United States)

^b WIL RESEARCH LABORATORIES   (United States)

^c SANOFI   (France)

^d MERCK RESEARCH LABORATORIES   (United States)

Author keywords

5a reductase; Antiandrogen; Development; Dihydrotestosterone; Finasteride; In utero exposure

Indexed keywords

ANDROGEN; ANDROGEN RECEPTOR; ANDROSTANOLONE; FINASTERIDE; STEROID 5ALPHA REDUCTASE; TESTOSTERONE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AUTOPSY; CONCENTRATION RESPONSE; CONTROLLED STUDY; ECTOPIC TESTIS; ENZYME ACTIVITY; ENZYME INHIBITION; GENITAL MALFORMATION; GESTATIONAL AGE; HYPOSPADIAS; MALE; MALE GENITAL SYSTEM; METHODOLOGY; NIPPLE MALFORMATION; NONHUMAN; ORGANOGENESIS; PREDICTION; PRENATAL EXPOSURE; PROSTATE; RAT;

ABNORMALITIES, DRUG-INDUCED; ADMINISTRATION, ORAL; ANDROGEN ANTAGONISTS; ANDROGENS; ANIMALS; ANIMALS, NEWBORN; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; FEMALE; FINASTERIDE; GENITALIA, MALE; MALE; MATERNAL EXPOSURE; NIPPLES; PREGNANCY; PRENATAL EXPOSURE DELAYED EFFECTS; RATS; RATS, SPRAGUE-DAWLEY; SEXUAL MATURATION; TERATOGENS;

ANIMALIA;

EID: 0043092172     PISSN: 10966080     EISSN: None     Source Type: Journal    
DOI: 10.1093/toxsci/kfg128     Document Type: Article

References (33)

1. Barlow, N. J., McIntyre, B. S., and Foster, P. M. D. (2002). Permanent alteration of anogenital distance and nipple retention in male rats exposed to di(n-butyl) phthalate in utero. Toxicol. Sci. 66(Suppl.), 233 (Abstract).
2. Berman, D. M., Tian, H., and Russell, D. W. (1995). Expression and regulation of steroid 5α-reductase in the urogenital tract of the fetal rat. Mol. Endocrinol. 9, 1561-1570.
3. Blohm, T. R., Laughlin, M. E., Benson, H. D., Johnston, J. O., Wright, C. L., Schatzman, G. L., and Weintraub, P. M. (1986). Pharmacological induction of 5α-reductase deficiency in the rat: Separation of testosterone-mediated and 5α-dihydrotestosterone-mediated effects. Endocrinology 119, 959-966.
4. Clark, R. L., Anderson, C. A., Prahalada, S., Robertson, R. T., Lochry, E. A., Leonard, Y. M., Stevens, J. L., and Hoberman, A. M. (1993). Critical developmental periods for effects on male rat genitalia induced by finasteride, a 5α-reductase inhibitor. Toxicol. Appl. Pharmacol. 119, 34-40.
5. Clark, R. L., Antonello, J. M., Grossman, S. J., Wise, L. D., Anderson, C., Bagdon, W. J., Prahalada, S., MacDonald, J. S., and Robertson, R. T. (1990). External genitalia abnormalities in male rats exposed in utero to finasteride, a 5α-reductase inhibitor. Teratology 42, 91-100.
6. Foster, P. M. D., and McIntyre, B. S. (2002). Endocrine active agents: Implications of adverse and non-adverse changes. Toxicol. Pathol. 30, 59-65.
7. George, F. W. (1989). Developmental pattern of 5α-reductase activity in the rat gubernaculum. Endocrinology 124, 727-732.
8. George, F. W., Johnson, L., and Wilson, J. D. (1989). The effect of a 5α-reductase inhibitor on androgen physiology in the immature male rat. Endocrinology 125, 2434-2438.
9. George, F. W., and Peterson, K. G. (1988). 5α-Dihydrotestosterone formation is necessary for embryogenesis of the rat prostate. Endocrinology 122, 1159-1164.
10. Gloyna, R. E., and Wilson, J. D. (1969). A comparative study of the conversion of testosterone to 17β-hydroxy-5α-androstan-3-one (dihydrotestosterone) by prostate and epididymis. J. Clin. Endocrinol. Metab. 29, 970-977.
11. Gray, L. E., Ostby, J., Furr, J., Price, M., Veeramachaneni, D. N. R., and Parks, L. (2000). Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. Toxicol. Sci. 58, 350-365.
12. Gray, L. E., Jr., Ostby, J., Monosson, E., and Kelce, W. R. (1999a). Environmental antiandrogens: Low doses of the fungicide vinclozolin alter sexual differentiation of the male rat. Toxicol. Ind. Health 15, 48-64.
13. Gray, L. E., Jr., Wolf, C., Lambright, C., Mann, P., Price, M., Cooper, R. L., and Ostby, J. (1999b). 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.
14. Hanley, J. A., and McNeil, B. J. (1982). The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 143, 29-36.
15. Hellwig, J., van Ravenzwaay, B., Mayer, M., and Gembardt, C. (2000). Pre- and postnatal oral toxicity of vinclozolin in Wistar and Long-Evans rats. Regul. Toxicol. Pharmacol. 32, 42-50.
16. Imperato-McGinley, J., Binienda, Z., Arthur, A., Mininberg, D. T., Vaughan, E. D., Jr., and Quimby, F. W. (1985). The development of a male pseudohermaphroditic rat using an inhibitor of the enzyme 5α-reductase. Endocrinology 116, 807-812.
17. Imperato-McGinley, J., Binienda, Z., Gedney, J., and Vaughan, E. D., Jr. (1986). Nipple differentiation in fetal male rats treated with an inhibitor of the enzyme 5α-reductase: definition of a selective role for dihydrotestosterone. Endocrinology 118, 132-137.
18. Imperato-McGinley, J., Sanchez, R. S., Spencer, J. R., Yee, B., and Vaughan, E. D. (1992). Comparison of the effects of the 5α-reductase inhibitor finasteride and the antiandrogen flutamide on prostate and genital differentiation: Dose-response studies. Endocrinology 131, 1149-1156.
19. Jegou, B., Peake, R. A., Irby, D. C., and de Kretser, D. M. (1984). Effects of the induction of experimental cryptorchidism and subsequent orchidopexy on testicular function in immature rats. Biol. Reprod. 30, 179-187.
20. Kratochwil, K. (1977). Development and loss of androgen responsiveness in the embryonic rudiment of the mouse mammary gland. Dev. Biol. 61, 358-365.
21. Latendresse, J. R., Warbrittion, A. R., Jonassen, H, and Creasy, D. M. (2002). Fixation of testes and eyes using a modified Davidson's fluid: Comparison with Bouin's fluid and conventional Davidson's fluid. Toxicol. Pathol. 30, 524-533.
22. McIntyre, B. S., Barlow, N. J., and Foster, P. M. D. (2001). Androgen-mediated development in male rat offspring exposed to flutamide in utero: Permanence and correlation of early postnatal changes in anogenital distance and nipple retention with malformations in androgen-dependent tissues. Toxicol. Sci. 62, 236-249.
23. McIntyre, B. S., Barlow, N. J., and Foster, P. M. D. (2002). Male rats exposed to linuron in utero exhibit permanent changes in anogenital distance, nipple retention, and epididymal malformations that result in subsequent testicular atrophy. Toxicol. Sci 65, 62-70.
24. McIntyre, B. S., Barlow, N. J., Wallace, D. G., Maness, S. C., Gaido, K. W., and Foster, P. M. D. (2000). Effects of in utero exposure to linuron on androgen-dependent reproductive development in the male Crl:CD(SD)BR rat. Toxicol. Appl. Pharmacol. 167, 87-99.
25. Medical Economics Company (2002). Physician's Desk Reference, 56th ed., pp. 2172-2178. Medical Economics Company, Inc., Montvale, New Jersey.
26. Mylchreest, E., Sar, M., Cattley, R. C., and Foster, P. M. D. (1999). Disruption of androgen-regulated male reproductive development by di(n-butyl) phthalate during late gestation in rats is different from flutamide. Toxicol. Appl. Pharmacol. 156, 81-95.
27. Mylchreest, E., Wallace, D. G., Cattley, R. C., and Foster, P. M. D. (2000). Dose-dependent alterations in androgen-regulated male reproductive development in rats exposed to di(n-butyl) phthalate during late gestation. Toxicol. Sci. 55, 143-151.
28. National Research Council (1996). Guide for the Care and Use of Laboratory Animals. National Academy Press, Washington, DC.
29. 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.
30. Spencer, J. R., Torrado, T., Sanchez, R. S., Vaughan, E. D., Jr., and Imperato-McGinley, J. (1991). Effects of flutamide and finasteride on rat testicular descent. Endocrinology 129, 741-748.
31. Turner, K. J., Barlow, N. J., Struve, M. F., Wallace, D. G., Gaido, K. W., Dorman, D. C., and Foster, P. M. D. (2002). Effects of in utero exposure to the organophosphate insecticide fenitrothion on androgen-dependent reproductive development in the Crl:CD(SD)BR rat. Toxicol. Sci. 68, 174-183
32. Veyssiere, G., Berger, M., Jean-Faucher, C., de Turckheim, M., and Jean, C. (1982). Testosterone and dihydrotestosterone in sexual ducts and genital tubercle of rabbit fetuses during sexual organogenesis: Effects of fetal decapitation. J. Steroid Biochem. 17, 149-154.
33. Wilson, J. D., and Lasnitzki, I. (1971). Dihydrotestosterone formation in fetal tissues of the rabbit and rat. Endocrinology 89, 659-668.