Genetic Control of Levels of Murine Kidney Glucuronidase mRNA in Response to Androgen

• Published in: Proceedings of the National Academy of Sciences - PNAS 1983-12, Vol.80 (24), p.7596-7600
• Main Authors: Palmer, Robbin, Gallagher, Patricia M., Boyko, William L., Ganschow, Roger E.
• Format: Article
• Language: English
• Subjects: Alleles; Androgens; Animals; Cloning, Molecular; Complementary DNA; DNA; DNA - metabolism; Genes - drug effects; Glucuronidase - genetics; Haplotypes; Kidney - enzymology; Kidneys; Messenger RNA; Mice; Mice, Inbred Strains; Nucleic Acid Hybridization; Plasmids; Protein Biosynthesis; RNA; RNA, Messenger - genetics; Testosterone - pharmacology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.80.24.7596

A cis-acting genetic element, designated Gus-r, regulates the androgen-induced rates of murine glucuronidase (EC 3.2.1.31) synthesis in kidney tubule cells and is tightly linked to the glucuronidase structural gene, Gus-s. To investigate the molecular mechanism underlying this regulation, we have cloned a glucuronidase-specific cDNA sequence in plasmid pBR322. This cloned DNA has been utilized as a probe in blot hybridization analyses to determine whether the control of androgen responsiveness of kidney glucuronidase synthesis by Gus-r is exerted over the level or the translatability of glucuronidase mRNA. Three important observations emerged from these studies: (i) glucuronidase mRNA exists as a single size class of approximately 2,800 nucleotides; (ii) androgen stimulation of glucuronidase synthesis is directly related to the level of glucuronidase mRNA; and (iii) strain differences in levels of kidney glucuronidase mRNA accumulated in response to androgen are controlled by alleles of Gus-r. Thus, Gus-r regulates the androgen responsiveness of glucuronidase synthesis by controlling the amount of glucuronidase mRNA available for translation and is a cis-acting genetic element that regulates the hormonal responsiveness of a specific mRNA.