Flutamide as a tool to study the hormonal regulation of the reproductive tract in the golden hamster

Abstract

S u m m a r y . The effect of flutamide (FLU) administered during 6 weeks at doses of 50 or 100 mg kg-' body weight, on various reproductive characteristics of sexually active male golden hamsters was studied. The weight of seminal vesicles and epididymides showed a dose dependent inhibition with FLU, while testicular weight exhibited a biphasic response, its value being increased by 20% at lower FLU doses and reduced by 15% at higher FLU doses. An elevation of testicular and epididymal androgen-binding protein (ABP) content and also of testicular testosterone content was observed with both doses of FLU. Serum levels of LH and testosterone exhibited a four-fold increase, at both doses of FLU, while FSH serum level was elevated depending on the dose of FLU used. Results suggest that in the golden hamster the maintenance of the weight of testes and accessory organs depends mainly on androgenic stimulation, while production and transport of ABP is probably regulated by gonadotropins.

Short‐Term Antiandrogen Flutamide Treatment Causes Structural Alterations in Somatic Cells Associated with Premature Detachment of Spermatids in the Testis of Pubertal and Adult Guinea Pigs

“…(1978) demonstrated an inhibitory effect on the spermatogenesis of mice treated with 0.2–2 mg of flutamide/kg of body weight, which is more accentuated in short periods of treatment. The inhibitory effect of flutamide on the activity of other accessory organs of the reproductive apparatus of rodents is also well known (Balbotin 1994) and, recently, Cordeiro et al. (2004), utilizing the same experimental conditions, demonstrated the inhibitory action of flutamide on testosterone and its action on prostate.…”

“…Previous studies have shown the efficacy of non‐steroidal antiandrogen, flutamide in the blockage of the testicular action of testosterone in adult rodents (Vojtísková et al. 1978; Balbotin 1994). On the basis of the lower frequency of tubules containing spermatozoa and the number of epididymal spermatozoids, Vojtísková et al.…”

Flutamide treatment reveals a relationship between steroidogenic activity of Leydig cells and ultrastructure of their mitochondria

“…It has been repeatedly shown that compounds with anti-androgenic activity (including flutamide) have the potential to adversely affect human and animal reproduction leading to several disorders of male reproductive system in adulthood 28 – 30 . Substantial increases in plasma LH and testosterone concentrations shortly after acute treatment with flutamide were reported in studies on male rats and hamsters 31 , 32 . Several further experiments showed that anti-androgens (and specifically flutamide) disturbing ability of testosterone receptor binding, lead not only to weakening of the negative feedback of testosterone on the HPG axis but also induce impairment of cellular processes controlling spermatogenesis and steroidogenesis in testes, both of humans and animals 33 , 34 (for review see 35 ).…”

The influence of reproductive hormones on the torpor patterns of the marsupial Sminthopsis macroura: Bet-hedging in an unpredictable environment

“…This contrasts with other mammals, where testes maintenance is dependent on circulating testosterone [12,48]. However, the insignificant effects of either testosterone or flutamide on the accessory reproductive tract contrasts to other studies on marsupials [46,10], rodents [37,1,76] and fish [3] although in other studies higher doses of flutamide were used to initiate a significant response [1,76]. Independence of the accessory tract to testosterone may suit the life history pattern of this marsupial genus, where males can move large distances, and females are more likely to hold territories when reproducing [55,21].…”

“…This was also true for DMR and NMR. There are surprisingly few data on the effects of flutamide on metabolism, with a focus on body condition and reproductive disruption rather than cellular metabolism [1,76]. Interestingly, compartmentalisation of MR during the daily cycle occurred, with ADMR unaffected in females, but DMR significantly increased under LD 10:14 with progesterone treatment and NMR significantly increased under LD 14:10 with either tamoxifen or RU486.…”