Growth hormone and insulin-like growth factor-I enhance beta-glucuronidase gene activation by androgen in mouse kidney.
Beta-glucuronidase (GUS) is a lysosomal enzyme that, in mouse kidney, is subject to control by multiple hormones: androgen, which increases GUS transcription; estrogen, which antagonizes androgen-mediated stimulation of GUS; and growth hormone (GH), which appears to be necessary for the full androgen effect. Neither estrogen nor GH affects GUS in the absence of androgen. In hypophysectomized or pituitary dwarf mice the reduced androgen stimulation of GUS can be partially restored with GH treatment. Androgen-induced GUS mRNA increased significantly with intermittent GH, compared to no GH or continuous GH. Intact mice subjected to continuous infusion of GH showed a depressed androgen effect on GUS similar to that seen in GH-deficient mice. Thus, pulsatile GH is required for the full androgen response. Insulin-like growth factor-I (IGF-I) also restored GUS induction by androgen in GH-deficient mice. We conclude that GH enhances the effect of androgen on the GUS gene via IGF-I. Using transgenic mice, we have also identified a genetic variant of the GUS gene that is insensitive to GH enhancement of the androgen effect.
Niermann
G L
GL
Children's Hospital Oakland Research Institute, CA 94609, USA.
Watson
G L
GL
D000818:Animals; D004392:Dwarfism / Q000201:enzymology; D005260:Female; D005966:Glucuronidase / Q000235:genetics*; D013006:Growth Hormone / Q000008:administration & dosage / Q000172:deficiency / Q000494:pharmacology*; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009919:Orchiectomy; D010507:Periodicity; D012333:RNA, Messenger / Q000096:biosynthesis; D013739:Testosterone / Q000494:pharmacology
D012333:RNA, Messenger; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D005966:Glucuronidase