Weak androgen reduces the rate constant of β-glucuronidase induction

Abstract

Administration of androgen to mice induces kidney β-glucuronidase. Measuring β-glucuronidase activity, rate of β-glucuronidase synthesis, β-glucuronidase mRNA activity and β-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, k a , a lower final extent of induction, and a slightly lower turnover constant, k b . 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 β-glucuronidase protein and β-glucuronidase mRNA indicates that the response to androgen is regulated at a pre-translational level. That substitution of MPA for DHT decreases k a , rather than increasing k b , suggests that induction of β-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 β-glucuronidase induction are dependent on the concentration of receptor molecules in the active conformational state.