Corticosterone induces rat liver alcohol dehydrogenase mRNA but not enzyme protein or activity.
Glucocorticoids induced ADH activity and mRNA 2- to 4-fold in rat hepatoma cells (H4IIE and H4IIEC3), but were reported not to alter ADH activity in rat liver. The failure of corticosteroids to induce ADH may have been due to the short-term treatment of the rats or the dose of steroid used. To reevaluate the effect of glucocorticoids in vivo, we studied animals 4.5 weeks after adrenalectomy so that ADH activity and mRNA should have reached a new steady-state level; the dose of glucocorticoid used was estimated to provide physiological replacement. Male Wistar rats were injected with a single daily dose (10 mg/kg/day) of corticosterone-21-acetate or vehicle subcutaneously for 10 days. Liver extracts were assayed for ADH activity, ADH protein, and ADH mRNA. Nuclei were isolated for nuclear run-on assays. Adrenalectomy did not reduce the activity of ADH in liver. Subsequent corticosterone treatment did not alter ADH enzyme activity, nor did it affect ADH protein levels as analyzed on Western blots. However, Northern blot analysis of ADH mRNA indicated a 2-fold increase in ADH mRNA in the treated animals when the data were normalized to the level of the 28S ribosomal RNA or CHO-B mRNA. The rate of transcription of the ADH gene in nuclei isolated at the end of 10 days of treatment from corticosterone-treated adrenalectomized rats was not statistically different from that in the oil-treated adrenalectomized ones. The disparity between ADH activity and protein levels and the mRNA level may have resulted from other effects of corticosterone, e.g., stimulation of protein degradation or effects on translation.
Qulali
M
M
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202-5121.
Crabb
D W
DW
D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000818:Animals; D003345:Corticosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D007279:Injections, Subcutaneous; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011921:Rats, Inbred WKY
D012333:RNA, Messenger; D000426:Alcohol Dehydrogenase; C029939:corticosterone acetate; D003345:Corticosterone