The effects of flutamide on cell-cell junctions in the testis, epididymis, and prostate

Hejmej, Anna; Bilińska, Barbara

doi:10.1016/j.reprotox.2018.06.014

Cited by 37 publications

(16 citation statements)

References 218 publications

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“…Different letters over each bar indicate significant pairwise differences. See also "Results" and Table 2 for full descriptive statistics Hejmej and Bilinska 2018). Similar findings have been reported in frogs (Bhatia et al 2014) and fishes (Orton et al 2018).…”

Section: Tablesupporting

confidence: 76%

Life-long testosterone and antiandrogen treatments affect the survival and reproduction of captive male red-legged partridges (Alectoris rufa)

Alonso‐Álvarez¹,

Cantarero²,

Romero-Haro³

et al. 2020

Behav Ecol Sociobiol

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Sexual steroids can play an important role as life-history organizers. In males, high circulating testosterone levels induce physiological/behavioral costs and benefits, leading to trade-offs. However, studies simultaneously testing the impact of these levels in both fitness components (survival and fecundity) during lifetime are scarce and limited to wild birds. To determine the mortality causes or hormonal manipulation impacts on male fertility is, nonetheless, a difficult task in free-ranging animals that could be easier in captivity. We longitudinally monitored captive red-legged partridges (Alectoris rufa) and exposed males to high exogenous testosterone levels, anti-androgens, or a control treatment during each breeding period throughout their lives. Theory predicts that individuals maintaining high androgen levels should obtain higher fitness returns via reproduction, but suffer reduced longevity. Testosterone-treated male partridges, accordingly, lived shorter compared to controls, since they were more prone to die from a natural bacterial infection. However, the same birds seemed to have a lower capacity to fertilize eggs, probably due to endocrine feedback reducing testicular mass. These results show that exogenous testosterone can exert unpredicted effects on fitness parameters. Therefore, caution must be taken when drawing conclusions from non-fully controlled experiments in the wild. Males treated with the androgen-receptor blocker flutamide did not outlive controls as predicted by the life-history trade-off theory, but their mates laid eggs with higher hatching success. The latter could be due to mechanisms improving sperm quality/quantity or influencing maternal investment in egg quality. Testosterone receptor activity/amount could thus be as relevant to fitness as testosterone levels. Significance statement It has repeatedly been hypothesized that high testosterone levels induce a cost in terms of reduced lifetime reproductive success. This can be due to reduced fecundity or via shorter lifespan. This is, however, only supported by a handful of studies, mostly in wild birds. We tested this in captive male red-legged partridges, which allowed us to determine reproductive success and mortality causes. We increased testosterone levels or blocked its action with antiandrogens throughout life. High testosterone levels reduced the survival by making birds more prone to die by infection. The eggs produced by their mates also showed lower Electronic supplementary material The online version of this article (

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Section: Tablesupporting

confidence: 76%

Life-long testosterone and antiandrogen treatments affect the survival and reproduction of captive male red-legged partridges (Alectoris rufa)

Alonso‐Álvarez¹,

Cantarero²,

Romero-Haro³

et al. 2020

Behav Ecol Sociobiol

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“…In addition, flutamide is considered to inhibit AR singling through blocking AR's binding to its ligand like testosterone or dihydrotestosterone [29], and in the current study flutamide was found to reverse the training-induced increases of AR in muscles, suggested that flutamide might inhibit AR signaling through down-regulating the protein level of AR in tissue, except for the well-known blockade of binding with testosterone. Similar result was reported by a recent study which revealed the inhibitive function of flutamide by downregulating AR protein in tissues [10].…”

Section: Flutamide Reversed the Training-induced Selective Increases supporting

confidence: 55%

Crucial role of androgen receptor in resistance and endurance trainings-induced muscle hypertrophy through IGF-1/IGF-1R- PI3K/Akt- mTOR pathway

Yin

Lin

et al. 2020

Nutr Metab (Lond)

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Background: Androgen receptor (AR) has been reported to play vital roles in exercise-induced increase of muscle mass in rats, but needs to be further verified and the mechanism behind remains unclear. As AR target genes, insulin growth factor-1 (IGF-1) and IGF-1 receptor (IGF-1R) promote muscle hypertrophy through activating PI3K/ Akt-mammalian target of rapamycin (mTOR) pathway, a classic pathway of muscle hypertrophy. So the main purpose of this study was using AR antagonist flutamide to demonstrate AR's effect on training-induced muscle hypertrophy and its possible mechanism: IGF-1/IGF-1R-PI3K/Akt-mTOR pathway? Methods: Forty-eight Sprague Dawley male rats aged 7 weeks were randomly divided into six groups: control (C), flutamide (F), resistance training (R), resistance training plus flutamide (R + F), endurance training (E), and endurance training plus flutamide (E + F) groups. Flutamide was used to block AR in rats. Rats in R and R + F groups fulfilled 3 weeks of ladder climbing with progressively increased load, while E and E + F rats completed 3-week moderate intensity aerobic exercise on a treadmill. The relative muscle mass (muscle mass/body weight) of rats was detected. Serum levels of testosterone and IGF-1 of rats were determined by ELISA, and mRNA levels of IGF-1R and mTOR in muscles by real-time PCR. Protein levels of AR, IGF-1, IGF-1R, mTOR, PI3K, Akt, p-PI3K and p-Akt in muscles were detected by Western blot. Results: (1) The training-induced rise in the relative muscle mass and the expression levels of AR were only found in the gastrocnemius of R rats and in the soleus of E rats (selective muscle hypertrophy), which were blocked by flutamide. (2) Serum testosterone in the R and E rat were increased, and flutamide exerted no effect. (3) The levels of IGF-1, IGF-1R and mTOR as well as the activities of PI3K and Akt were enhanced selectively (in the gastrocnemius of R rats and in the soleus of E rats), which were reduced by flutamide. Conclusions: AR exerted an essential role in both resistance training and endurance training-induced muscle hypertrophy, which was mediated at least partly through IGF-1/IGF-1R-PI3K/Akt-mTOR pathway.

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“…In addition, flutamide is considered to inhibit AR singling through blocking AR's binding to its ligand like testosterone or dihydrotestosterone [29] , and in the current study flutamide was found to reverse the training-induced increases of AR in muscles, suggested that flutamide might inhibit AR signaling through down-regulating the protein level of AR in tissue, except for the well-known blockade of binding with testosterone. Similar result was reported by a recent study which revealed the inhibitive function of flutamide by down-regulating AR protein in tissues [10] .…”

Section: Crucial Effects Of Ar In Training-induced Selective Muscle Hsupporting

confidence: 55%

Crucial role of androgen receptor in resistance and endurance trainings-induced muscle hypertrophy through IGF-1/IGF-1R- PI3K/Akt- mTOR pathway

Yin

Lin

et al. 2020

Preprint

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Objective Androgen receptor (AR) has been reported to play vital roles in exercise-induced increase of muscle mass in rats, but needs to be further verified and the mechanism behind remains unclear. As AR target genes, insulin growth factor-1 (IGF-1) and IGF-1 receptor (IGF-1R) promote muscle hypertrophy through activating PI3K/Akt- mammalian target of rapamycin (mTOR) pathway, a classic pathway of muscle hypertrophy. So the main purpose of this study was using AR antagonist flutamide to demonstrate AR’s effect on training-induced muscle hypertrophy and its possible mechanism: IGF-1/IGF-1R- PI3K/Akt- mTOR pathway? Methods Forty-eight Sprague Dawley male rats aged seven weeks were randomly divided into six groups: control (C), flutamide (F), resistance training (R), resistance training plus flutamide (R+F), endurance training (E), and endurance training plus flutamide (E+F) groups. Flutamide was used to block AR in rats. Rats in R and R+F groups fulfilled 3 weeks of ladder climbing with progressively increased load, while E and E+F rats completed 3-week moderate intensity aerobic exercise on a treadmill. The relative muscle mass (muscle mass/body weight) of rats was detected. Serum levels of testosterone and IGF-1 of rats were determined by ELISA, and mRNA levels of IGF-1R and mTOR in muscles by real-time PCR. Protein levels of AR, IGF-1, IGF-1R, mTOR, PI3K, Akt, p-PI3K and p-Akt in muscles were detected by Western blot. Results (1) The training-induced rise in the relative muscle mass and the expression levels of AR were only found in the gastrocnemius of R rats and in the soleus of E rats (selective muscle hypertrophy), which were blocked by flutamide. (2) Serum testosterone in the R and E rat were increased, and flutamide exerted no effect. (3) The levels of IGF-1, IGF-1R and mTOR as well as the activities of PI3K and Akt were enhanced selectively (in the gastrocnemius of R rats and in the soleus of E rats), which were reduced by flutamide. Conclusions AR exerted an essential role in both resistance training and endurance training-induced muscle hypertrophy, which was mediated at least partly through IGF-1/IGF-1R- PI3K/Akt- mTOR pathway.

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The effects of flutamide on cell-cell junctions in the testis, epididymis, and prostate

Cited by 37 publications

References 218 publications

Life-long testosterone and antiandrogen treatments affect the survival and reproduction of captive male red-legged partridges (Alectoris rufa)

Life-long testosterone and antiandrogen treatments affect the survival and reproduction of captive male red-legged partridges (Alectoris rufa)

Crucial role of androgen receptor in resistance and endurance trainings-induced muscle hypertrophy through IGF-1/IGF-1R- PI3K/Akt- mTOR pathway

Crucial role of androgen receptor in resistance and endurance trainings-induced muscle hypertrophy through IGF-1/IGF-1R- PI3K/Akt- mTOR pathway

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