Specificity of androgen resistance in Mus caroli kidney.
Androgen controls the expression of beta-glucuronidase and several other proteins in the kidney of the standard laboratory mouse, Mus musculus. Other species within the genus Mus exhibit a variety of response patterns for kidney beta-glucuronidase and other markers of androgen action. We have investigated the mechanism of androgen action in M. caroli, a Mus species that does not produce beta-glucuronidase in response to testosterone. The failure of testosterone to induce beta-glucuronidase in M. 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 beta-glucuronidase in M. musculus females and kidney ornithine decarboxylase, submandibular gland renin, and submandibular gland epidermal growth factor in both M. caroli and M. musculus females. Furthermore, kidney androgen receptor proteins from M. caroli and M. musculus animals have the same sedimentation characteristics on sucrose density gradients. These data indicate that androgen resistance in M. caroli is not due to deficient 5 alpha-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 beta-glucuronidase in M. caroli kidney to induction by androgen occurs at the level of the beta-glucuronidase gene.
Wilson
C M
CM
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235.
Kimberlin
D F
DF
Griffin
J E
JE
Wilson
J D
JD
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D004351:Drug Resistance / Q000235:genetics; D004815:Epidermal Growth Factor / Q000235:genetics; D005260:Female; D005966:Glucuronidase / Q000235:genetics; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008805:Mice, Inbred A / Q000235:genetics; D008810:Mice, Inbred C57BL / Q000235:genetics; D009115:Muridae / Q000235:genetics*; D009955:Ornithine Decarboxylase / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000235:genetics; D013363:Submandibular Gland / Q000378:metabolism
D000728:Androgens; D011944:Receptors, Androgen; D004815:Epidermal Growth Factor; D005966:Glucuronidase; D012083:Renin; D009955:Ornithine Decarboxylase