THE GUS-E LOCUS REGULATES ESTROGEN REPRESSION OF ANDROGEN-INDUCED BETA-GLUCURONIDASE EXPRESSION IN MOUSE KIDNEY

Both enzyme activity and mRNA concentration of beta-glucuronidase were measured in kidneys of mice treated with testosterone and the synthet ic estrogen, diethylstilbestrol. Six congenic strains, all having a C5 7BL6/J genetic background but each having a different haplotype of the beta-glucuronidase gene complex, were compared In each strain the ind uction caused by androgen was partially repressed by estrogen. The ext ent of this antagonism varied among the six haplotypes and was not coo rdinate with the extent of induction by androgen alone. Antagonism app ears to be regulated by at least two alleles of a new locus, Gus-e, wi thin the beta-glucuronidase gene complex. Repression by estrogen, like induction by androgen, appears to take place primarily at the transcr iptional level. Kinetic studies revealed that estrogen causes the andr ogen response curve to plateau earlier and at a lower level. This sugg ests that estrogen increases the rate of gene deactivation rather than decreasing the rate of gene activation. Isoelectric focusing of beta- glucuronidase from Gus-e(a) and Gus-e(b) mice and their F1 progeny rev ealed that the genes are regulated in cis. Together, these findings su pport a model in which both sex hormones exert their effects on separa te DNA response elements located in close proximity to the gene or wit hin the gene itself