Androgen and progestin stimulation of ornithine decarboxylase activity in the mouse kidney.
This study was designed to characterize mouse kidney ornithine decarboxylase (ODC) activity as an androgenic end point and to use ODC activity to detect an androgenic effect of antiandrogens. Enzyme activity was not affected by freezing the whole kidney or the 15,000 X g supernatant for up to 7 days. ODC activity in female mice had a diurnal variation that peaked at midday. This diurnal variation did not affect the androgenic response of ODC. Enzyme activity was lower in females than in males and, in both sexes, could be induced further to similar levels with testosterone treatment. A single dose of crystalline testosterone induced a marked increase in activity, which peaked sharply, up to 100-fold above baseline, 12-17 h after treatment. Enzyme activity could be maintained with continued treatment for at least 28 days and reached levels up to 1,000-fold above baseline. The response was specific for androgens and required a functional androgen receptor. Other hormones had permissive effects. The early androgen-stimulated response (less than 24 h) was partially diminished by hypophysectomy. Propylthiouracil reduced both early and chronic responses. Genetic factors were also involved. The testosterone-stimulated response of C57BL/6J mice was consistently approximately half that of DBA/2J mice. Using this very specific and sensitive increase in ODC activity as an end point, we did not detect an androgenic response to treatment with the antiandrogens, cyproterone acetate (6-chloro - 17 alpha - acetoxyl - 1,2 alpha - methylene - 4,6- pregnadiene- 3,20-dione) and flutamide (4'-nitro-3'-trifluoromethylisobutyranilide), despite an increase in RNA polymerase activity. The functionality of the polymerase activity induced by antiandrogens thus remains in question. These data suggest that mouse renal ODC activity can be a useful tool for future study of androgen action at the physiological and molecular level.
D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D002940:Circadian Rhythm; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology*; D007016:Hypophysectomy; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011372:Progestins / Q000494:pharmacology*; D011441:Propylthiouracil / Q000494:pharmacology; D011944:Receptors, Androgen / Q000378:metabolism; D013045:Species Specificity; D013739:Testosterone / Q000494:pharmacology*
D011372:Progestins; D011944:Receptors, Androgen; D013739:Testosterone; D004997:Ethinyl Estradiol; D011441:Propylthiouracil; D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase; D006854:Hydrocortisone