Effects of the chronic use of finasteride on testicular weight and spermatogenesis in Wistar rats

Rhoden, Ernani Luı́s; Gobbi, Daniel; Menti, Eduardo; Rhoden, Cláudia Ramos; Telöken, Cláudio

doi:10.1046/j.1464-410x.2002.02785.x

Cited by 18 publications

(14 citation statements)

References 9 publications

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“…According to these results, it was shown in male rats during puberty that a peak of 5-a reductases and 5-a-reduced metabolites coincided with the first wave of spermatogenesis, suggesting a role for 5-a reductases in the initiation of spermatogenesis (Killian et al 2003). In studies during adulthood, no effects of FIN on testicular histomorphology were found in rats (George et al 1989, Rhoden et al 2002 and dogs (Juniewicz et al 1993). By contrast, a study performed in adult rats showed that administration of FIN suppressed the testosterone-induced restoration of spermatogenesis and demonstrated clearly a role for 5-a-reduced androgens in adult spermatogenesis (O'Donnell et al 1996).…”

Section: Discussionmentioning

confidence: 90%

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

Urbatzka¹,

Watermann²,

Lutz³

et al. 2009

Journal of Molecular Endocrinology

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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-a reductases might play a significant role in androgen-mediated reproductive biology. To test the involvement of 5-a reductases in maturation of gametes in amphibians, Xenopus laevis was exposed to finasteride (FIN), a known inhibitor of 5-a 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 LHb mRNA and a decrease of FSHb 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-a 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 testosteroneCFIN 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 LHb was observed on males and females. This study provides evidence that exposure of X. laevis to FIN, an inhibitor of 5-a reductases, impaired spermatogenesis and involved sex-specific hypophyseal feedback mechanisms.

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Section: Discussionmentioning

confidence: 90%

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

Urbatzka¹,

Watermann²,

Lutz³

et al. 2009

Journal of Molecular Endocrinology

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“…Overstreet et al 10 investigating humans and Rhoden et al 11 investigating rats, did not show any alterations in the spermatogenesis after treatment with finasteride. Overstreet et al 10 evaluated the ejaculate from young men under use of finasteride 1mg and compared them to a control group.…”

Section: Discussionmentioning

confidence: 93%

The effect of finasteride on spermatogenesis of Mesocricetus auratus

et al. 2008

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RESUMOObjetivo: Estudar o impacto da finasterida na espermatogênese do Mesocricetus auratus, adulto. Métodos: Foram avaliados 20 hamsters adultos, com idades superiores a 1 ano, distribuídos em dois grupos: grupo controle com dez animais (n=10) e grupo experimental também com dez animais (n=10). No grupo experimental foi aplicado 7,14ng/mL (0,5mL) de finasterida por 100mg/Kg/peso, subcutâneo (SC), na região dorsal do animal, três vezes por semana por 90 dias, dose correspondente a 5mg da droga usada em homens adultos, para tratamento da hiperplasia benigna da próstata (HBP). No final de três meses, esses Hamsters foram mortos por hipovolemia, após serem anestesiados com cloridrato de quetamina, na dosagem de 200 mg/kg juntamente com diazepam, na dosagem de 2,5 mg/kg. Os testículos foram retirados em monobloco juntamente com todo o aparelho geniturinário, fixados em formalina a 10% e encaminhados à histotécnica para posterior análise histológica em microscópico óptico. Foram usadas para coloração das lâminas a hematoxilina e eosina (HE). Resultados: Quando foram mortos, os Hamsters do grupo de controle pesaram em média 129,0g e desvio padrão (DP) de 18,8g. O grupo de experimento apresentou média de peso de 145,0g e DP de 15,25g. A idade dos animas de controle quando foram mortos apresentou média de 15,2 meses e DP de 1,13 meses. Os animais de experimento apresentaram média de idade de 17,16 meses e DP de 0,82. A diferença das médias de peso entre os dois grupos não teve significado estatístico (p=0,0514). Os animais (100%) do grupo controle não tiveram alterações tubulares e apresentaram todas as etapas da espermatogênese normais. Quatro animais (40%) do grupo de experimento apresentaram hipotrofia dos túbulos seminíferos, e seis (60%) desses animais apresentaram espermatogênese normal, mas diminuída em relação ao grupo controle. Do ponto de vista estatístico houve significância (p=0,043) entre o grupo de experimento e controle em relação às alterações testiculares. Conclusão: Os animais em uso de finasterida apresentaram atrofia tubulares significativas e diminuição da espermatogênese em comparação com o grupo-controle. Descritores: Mesocricetus. Finasterida, Testículo. Espermatogênese. ABSTRACT Purpose:To study the effect of finasteride on the spermatogenesis of adult Mesocricetus auratus. Methods: Twenty adult hamsters were evaluated. The animals were one year-older, and were randomly divided in 2 different groups: control group with ten animals (n=10) and experimental group also with ten animals (n=10). The animals in the experimental group were shot 7.14 ng/mL (0.5mL) of finasteride by 100mg/Kg, subcutaneously in the dorsal region three times per week during 90 days. This dose correspondes to 5mg of the drug used in adult men for the treatment of benign prostatic hyperplasia (BPH). After three months, the animals were anesthetized through association of 200mg/kg ketamine chloridrate and 2.5 mg/kg of diazepan and were dead through hypovolemia.. The testis removed along with the whole genitourinary apparel wer...

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“…However, this effect was felt to be secondary to inadequate copulatory plug formation, secondary to the drug's effects on seminal vesicles and the prostate (4,5). Further studies did not show an effect on spermatogenesis (6). Therefore, the effects of finasteride on fertility seen in rats were felt to be a species specific.…”

Section: Discussionmentioning

confidence: 99%