Weak androgen reduces the rate constant of beta-glucuronidase induction.
Administration of androgen to mice induces kidney beta-glucuronidase. Measuring beta-glucuronidase activity, rate of beta-glucuronidase synthesis, beta-glucuronidase mRNA activity and beta-glucuronidase mRNA concentration, the time course of induction was compared using a strong androgen, dihydrotestosterone (DHT), and a weakly androgenic progestin, medroxyprogesterone acetate (MPA). Using MPA resulted in a longer lag, a 3-4-fold slower rate of induction as defined by the forward rate constant, ka, a lower final extent of induction, and a slightly lower turnover constant, kb. Differences in kinetics of induction were consistent for all 4 measured parameters, and mimicked previously described genetic differences in these rate constants. The coordinate induction of beta-glucuronidase protein and beta-glucuronidase mRNA indicates that the response to androgen is regulated at a pre-translational level. That substitution of MPA for DHT decreases ka, rather than increasing kb, suggests that induction of beta-glucuronidase follows an increased rate of mRNA synthesis rather than a decreased rate of mRNA turnover. Finally, the results are consistent with a model in which the kinetic constants for beta-glucuronidase induction are dependent on the concentration of receptor molecules in the active conformational state.
D000818:Animals; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005966:Glucuronidase / Q000096:biosynthesis* / Q000235:genetics; D007700:Kinetics; D008525:Medroxyprogesterone / Q000494:pharmacology*; D051379:Mice; D008805:Mice, Inbred A; D012333:RNA, Messenger / Q000235:genetics
D012333:RNA, Messenger; D013196:Dihydrotestosterone; D005966:Glucuronidase; D008525:Medroxyprogesterone