Androgen and estrogen stimulation of ornithine decarboxylase activity in mouse kidney.
In the present work, the activity of mouse renal ornithine decarboxylase (ODC) from CBA female mice was used as a biological marker to detect (anti)androgenic activity of different groups of endocrine disruptors and steroids. Daily injections of testosterone or dihydrotestosterone (DHT) into 60 day old female mice for 4 days increased renal ODC activity in a dose-dependent manner that reached up to 100-fold (testosterone) or 250-fold (DHT) above the baseline when the highest dose, 200 microg/mouse, was used. Administration of flutamide concurrently with testosterone (75 microg/mouse) caused a potent decrease of ODC induction in a dose-dependent manner, suppressing the enzyme activity at the doses of 0.1 and 0.5 mg/mouse by about 88 and 95%, respectively. In contrast, estradiol at the doses of 0.5 and 1 mg/mouse induced a significant stimulation of renal ODC activity in a dose-dependent manner when it was given alone or in combination with testosterone. Using a sensitive increase in ODC activity in response to androgens as an end point, we did not detect an antiandrogenic effect of several antiandrogens, such as cyproterone acetate, spironolactone, p,p'DDE and vinclozolin. Also, none of these antiandrogens were able to change the basal level of renal ODC activity, with the exception of cyproterone acetate that at a dose of 0.1 mg/mouse stimulated ODC activity. The data obtained suggest that mouse renal ODC from CBA females is not strictly androgen-specific and cannot be used for estimation of antiandrogenic effects of compounds having an affinity to different types of receptors.
Department of Women and Child Health, Pediatric Endocrinology Unit (Q2:08), Karolinska Institute and Astrid Lindgren Childrens Hospital, S-171 76, Stockholm, Sweden.
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Svechnikov
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Ritzén
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Holst
D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D017373:Cyproterone Acetate / Q000494:pharmacology; D003633:Dichlorodiphenyl Dichloroethylene / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology*; D051379:Mice; D008808:Mice, Inbred CBA; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D010080:Oxazoles / Q000494:pharmacology; D013148:Spironolactone / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology*
D000726:Androgen Antagonists; D010080:Oxazoles; D013196:Dihydrotestosterone; D013148:Spironolactone; D013739:Testosterone; D017373:Cyproterone Acetate; D003633:Dichlorodiphenyl Dichloroethylene; D004958:Estradiol; D005485:Flutamide; D009955:Ornithine Decarboxylase; C025643:vinclozolin