Exposure of Xenopus laevis tadpoles to finasteride, an inhibitor of 5-alpha reductase activity, impairs spermatogenesis and alters hypophyseal feedback mechanisms.
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.
Urbatzka
R
R
Department of Inland Fisheries, IGB, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Berlin, Germany. rurbatzka@ciimar.up.pt
Watermann
B
B
Lutz
I
I
Kloas
W
W
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*
D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D037101:Luteinizing Hormone, beta Subunit; D018120:Finasteride; D005640:Follicle Stimulating Hormone