Estradiol-17 beta inhibition of androgen uptake, metabolism and binding in epididymis of adult male rats in vivo: a comparison with cyproterone acetate.
The effects of estradiol-17 beta on androgen uptake, metabolism and binding were studied in rat epididymis in vivo in comparison with cyproterone acetate. Steroids (250 ug/100 g body weight) were injected 5 min prior to 3H-testosterone in castrate rats. Estradiol-17 beta inhibited 3H-testosterone uptake into epididymal cytosol by 58% as compared to 38% by cyproterone acetate. 3H-Testosterone uptake into epididymal nuclei was inhibited 95% by estradiol-17 beta and 83% by cyproterone acetate. Total bound radioactivity in cytosol fractions was reduced to a greater extent by estradiol-17 beta than cyproterone acetate when either 3H-testosterone or 3H-dihydrotestosterone was injected. Binding of 3H-dihydrotestosterone to nuclear receptors was completely abolished by estradiol-17 beta; whereas approximately 20% binding remained in the nuclear extract after cyproterone acetate treatment. Metabolism of 3H-testosterone in vivo was also altered by estradiol-17 beta, resulting in diminished conversion to 3H-dihydrotestosterone. Cyproterone acetate, on the other hand, did not affect 3H-testosterone metabolism. Estradiol-17 beta and cyproterone acetate inhibited in vitro binding of 3H-dihydrotestosterone to the intracellular cytoplasmic receptor, but not the intraluminal androgen binding protein (ABP). These data suggest that estradiol-17 beta may have a more potent antiandrogenic effect on the epididymis than cyproterone acetate due to inhibition of 5 alpha reduction of testosterone as well as binding to the androgen receptor.
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003272:Contraceptive Agents, Male / Q000494:pharmacology*; D003534:Cyproterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017373:Cyproterone Acetate; D003600:Cytosol / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism*; D004822:Epididymis / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism*
D003272:Contraceptive Agents, Male; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D013739:Testosterone; D017373:Cyproterone Acetate; D004958:Estradiol; D003534:Cyproterone