title: Exposure of Xenopus laevis tadpoles to finasteride, an inhibitor of 5-alpha reductase activity, impairs spermatogenesis and alters hypophyseal feedback mechanisms.
abstract: 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 LHbeta mRNA and a decrease of FSHbeta 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 LHbeta 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.
authors: Department of Inland Fisheries, IGB, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Berlin, Germany. rurbatzka@ciimar.up.pt
authors: R
authors: R
authors: Urbatzka
authors: B
authors: B
authors: Watermann
authors: I
authors: I
authors: Lutz
authors: W
authors: W
authors: Kloas
mesh_terms: D058891:5-alpha Reductase Inhibitors; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D018120:Finasteride / Q000494:pharmacology*; D005640:Follicle Stimulating Hormone / Q000235:genetics; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007814:Larva; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics; D008297:Male; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D014982:Xenopus laevis / Q000502:physiology*
chemical_list: D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D037101:Luteinizing Hormone, beta Subunit; D018120:Finasteride; D005640:Follicle Stimulating Hormone