Faculty Research 1980 - 1989

Title

Weak androgen reduces the rate constant of beta-glucuronidase induction.

Document Type

Article

Publication Date

1985

Keywords

Enzyme-Induction: de, Female, Gene-Expression-Regulation: de, Glucuronidase: bi, ge, Kinetics, Medroxyprogesterone, Mice, Mice-Inbred-A, RNA-Messenger: ge, Stanolone, SUPPORT-U-S-GOVT-P-H-S

JAX Source

Mol Cell Endocrinol 1985 Jul; 41(2-3):179-85.

Grant

GM19521, GM31656, HD17666

Abstract

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.

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