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Journal of Molecular Endocrinology (2009) 43 209-219    DOI: 10.1677/JME-09-0058
© 2009 Society for Endocrinology

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Exposure of Xenopus laevis tadpoles to finasteride, an inhibitor of 5-{alpha} reductase activity, impairs spermatogenesis and alters hypophyseal feedback mechanisms

R Urbatzka1, B Watermann2, I Lutz1 and W Kloas1,3

1 Department of Inland Fisheries, IGB, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin, Germany
2 Limnomar, Bei der Neuen Muenze 11, 22145 Hamburg, Germany
3 Department of Endocrinology, Institute of Biology, Humboldt-University, Invalidenstrasse 43, 10115 Berlin, Germany

(Correspondence should be addressed to R Urbatzka who is now at Centre of Marine and Environmental Research, Rua dos Bragas 289, 4050-123 Porto, Portugal; Email: rurbatzka{at}ciimar.up.pt)

Sexual steroids have major regulatory functions in gonadal development, maturation of gametes and sexual differentiation in vertebrates. Previous studies in amphibians provided evidence that dihydrotestosterone and activity of 5-{alpha} reductases might play a significant role in androgen-mediated reproductive biology. To test the involvement of 5-{alpha} reductases in maturation of gametes in amphibians, Xenopus laevis was exposed to finasteride (FIN), a known inhibitor of 5-{alpha} reductase enzyme activity. In a long-term exposure from stage 46 to 66, severe disruption of spermatogenesis was observed in histological analysis of testes as detected by occurrence of empty spermatocysts, while ovaries remained unaffected. Real-time PCR analyses of male and female brain revealed an increase of LHβ mRNA and a decrease of FSHβ mRNA in males, suggesting a signalling on testes that could result in increased steroidogenesis and reduced Sertoli cell proliferation. Accordingly, the mRNA expression of P450 side chain cleavage enzyme and 5-{alpha} reductase type 2 was increased in testes, while no effects could be observed on steroidogenic genes in ovaries. A short-term exposure to testosterone, FIN and testosterone+FIN showed that transient effects of FIN targeted males selectively and, in particular, interfered with the hypothalamus–pituitary–gonad axis. Furthermore, a negative feedback of testosterone on LHβ was observed on males and females. This study provides evidence that exposure of X. laevis to FIN, an inhibitor of 5-{alpha} reductases, impaired spermatogenesis and involved sex-specific hypophyseal feedback mechanisms.







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