Genetic regulation of androgen-induced accumulation of mouse renal beta-glucuronidase messenger ribonucleic acid.
Mouse kidney beta-glucuronidase is induced by androgens in a receptor-dependent fashion. Genetic regulatory mutations have been described which govern this response. In mice carrying the Gus-ra allele (A/J), the induction of enzyme activity is 3-5 times greater than in animals with the Gus-rb allele (C57BL/6J). To study this hormonal and genetic control at the molecular level, we measured changes in beta-glucuronidase mRNA concentrations in these two mouse strains using cloned cDNA. The specificity of the regulation was assessed by following changes in the concentration of kidney androgen-regulated protein (KAP) mRNA, which is also under androgen control in mouse kidney. Female mice were treated with Silastic implants that released 120 micrograms testosterone/day over a 20-day time course. Induction of specific mRNA was analyzed by either Northern blot hybridization or a more quantitative assay in which renal poly(A) RNA was covalently bound to aminophenylthioether paper discs. The induction of beta-glucuronidase mRNA was about 10-fold higher in the strain carrying the Gus-ra regulatory allele, indicating that the Gus-r locus controls the beta-glucuronidase structural gene (Gus-s) at the level of mRNA accumulation. Regulation by Gus-r was specific for beta-glucuronidase mRNA as kidney androgen-regulated protein mRNA accumulation did not differ between these two strains of mice after androgen treatment.
D000818:Animals; D004262:DNA Restriction Enzymes; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005966:Glucuronidase / Q000235:genetics*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000502:physiology; D013739:Testosterone / Q000494:pharmacology*; D013997:Time Factors
D012333:RNA, Messenger; D011944:Receptors, Androgen; D013739:Testosterone; D004262:DNA Restriction Enzymes; D005966:Glucuronidase