Abstract
Androgen controls the expression of β-glucuronidase and several other proteins in the kidney of the standard laboratory mouse,Mus musculus. Other species within the genusMus exhibit a variety of response patterns for kidney β-glucuronidase and other markers of androgen action. We have investigated the mechanism of androgen action inM. caroli, aMus species that does not produce β-glucuronidase in response to testosterone. The failure of testosterone to induce β-glucuronidase inM. caroli females cannot be overcome by treatment with dihydrotestosterone, with pharmacological doses of testosterone propionate or dihydrotestosterone propionate, or with a variety of potent androgen analogues. All of these compounds induce kidney β-glucuronidase inM. musculus females and kidney ornithine decarboxylase, submandibular gland renin, and submandibular gland epidermal growth factor in bothM. caroli andM. musculus females. Furthermore, kidney androgen receptor proteins fromM. caroli andM. musculus animals have the same sedimentation characteristics on sucrose density gradients. These data indicate that androgen resistance inM. caroli is not due to deficient 5α-reductase or aberrant hormone metabolism producing suboptimal levels of functional androgen and is not caused by a defective androgen receptor. They suggest that the resistance of β-glucuronidase inM. caroli kidney to induction by androgen occurs at the level of the β-glucuronidase gene.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bardin, C. W., and Catterall, J. F. (1981). Testosterone: A major determinant of extragenital sexual dimorphism.Science 2111285.
Bullock, L. P. (1983). Androgen and progestin stimulation of ornithine decarboxylase activity in the mouse kidney.Endocrinology 1121903.
Catterall, J. F., Kontula, K. K., Watson, C. S., Seppänen, P. J., Funkenstein, B., Melanitou, E., Hickok, N. J., Bardin, C. W., and Jänne, O. A. (1986). Regulation of gene expression by androgens in murine kidney.Recent Prog. Horm. Res. 4271.
Dunn, J. F., and Wilson, J. D. (1975). Developmental study of androgen responsiveness in the submandibular gland of the mouse.Endocrinology 961571.
Houben, P. W., Bullock, L. P., and Fox, T. O. (1986). Differences in the androgen response between two mouse species.Biochem. Genet. 24805.
Isomaa, V., Pajunen, A. E. I., Bardin, C. W., and Jänne, O. A. (1982). Nuclear androgen receptors in the mouse kidney: Validation of a new assay.Endocrinology 111833.
Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951). Protein measurement with the Folin phenol reagent.J. Biol. Chem. 193265.
Lund, S. D., Miller, D., Chapman, V., and Ganschow, R. E. (1988). Androgen regulation of murine β-glucuronidase expression: Identification and characterization of a nonresponse variant.Genetics 119151.
Lusis, A. J., and Paigen, K. (1977). Relationships between levels of membrane-bound glucuronidase and the associated protein egasyn in mouse tissues.J. Cell Biol. 73728.
Mainwaring, W. I. P., and Mangan, F. R. (1973). A study of the androgen receptors in a variety of androgen-sensitive tissues.J. Endocrinol. 59121.
Murad, F., and Haynes, R. C., Jr. (1985). Androgens. In Goodman, A. G., Goodman, L. S., Rall, T. W., and Murad, F. (eds.),The Pharmacological Basis of Therapeutics Macmillan, New York, p. 1440.
Pegg, A. E., and McGill, S. (1979). Decarboxylation of ornithine and lysine in rat tissues.Biochim. Biophys. Acta 568416.
Swank, R. T., Paigen, K., and Ganschow, R. E. (1973). Genetic control of glucuronidase induction in mice.J. Mol. Biol. 81225.
Swank, R. T., Paigen, K., Davey, R., Chapman, V., Labarca, C., Watson, G., Ganschow, R., Brandt, E. J., and Novak, E. (1978). Genetic regulation of mammalian glucuronidase.Recent Prog. Horm. Res. 34401.
Tseng-Crank, J., and Berger, F. G. (1987). Evolution of steroid-inducibleRP2 mRNA expression in the mouse kidney.Genetics 116593.
Tseng-Crank, J., Schonfeld, C., and Berger, F. G. (1988). Evolution of androgen-regulated mRNA expression in mouse kidney.Mol. Biol. Evol. 5442.
Verhoeven, G., and Wilson, J. D. (1976). Cytosol androgen binding in submandibular gland and kidney of the normal mouse and the mouse with testicular feminization.Endocrinology 9979.
Walsh, P. C., and Wilson, J. D. (1976). The induction of prostatic hypertrophy in the dog with androstanediol.J. Clin. Invest. 571093.
Wilson, C. M., and Taylor, B. A. (1982). Genetic regulation of thermostability of mouse submaxillary gland renin.J. Biol. Chem. 257217.
Wilson, C. M., Erdös, E. G., Dunn, J. F., and Wilson, J. D. (1977). Genetic control of renin activity in the submaxillary gland of the mouse.Proc. Natl. Acad. Sci. USA 741185.
Wilson, C. M., Griffin, J. E., Reynolds, R. C., and Wilson, J. D. (1985). The interaction of androgen and thyroid hormones in the submandibular gland of the genetically hypothyroid (hyt/hyt) mouse.Endocrinology 1162568.
Wilson, J.D. (1987). Disorders of androgen action.Clin. Res. 351.
Author information
Authors and Affiliations
Additional information
This work was supported by Grant DK03892 from the National Institutes of Health.
Rights and permissions
About this article
Cite this article
Wilson, C.M., Kimberlin, D.F., Griffin, J.E. et al. Specificity of androgen resistance inMus caroli kidney. Biochem Genet 26, 705–716 (1988). https://doi.org/10.1007/BF02395517
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02395517