Estradiol regulates class I alcohol dehydrogenase gene expression in renal medulla of male rats by a post-transcriptional mechanism

Rat kidney contains alcohol dehydrogenase (ADH) activity which appears to be identical to the class I ADH expressed in liver. Treatment of male rats with estradiol for 10 days induced ADH activity and protein in the kidney approximately 3-fold. This was not the result of suppression of testosterone levels by estrogen, as castration did not increase ADH activity. In situ hybridization of kidney sections showed that ADH transcripts were localized to the medulla, that the basal level of mRNA is very low in the male, and that the induction of ADH mRNA by estradiol was approximately 10-fold. As estimated from Northern blot analysis, the induction of the mRNA was approximately 7-fold. Thus, induction of ADH mRNA substantially exceeded the increase in ADH activity and protein. Since the estradiol-treated rats lost weight relative to the oil-injected controls, the effect of starvation on ADH mRNA in kidney was examined. Starvation decreased kidney ADH activity by about 30% but increased mRNA about 2-fold. Time course experiments demonstrated induction of ADH mRNA by estradiol within 1 h with the maximum level achieved by 24 h. The transcription rate of the ADH gene as assessed by nuclear run-on assays performed at 1 and 24 h after treatment with estradiol was unchanged. We conclude that estradiol induces ADH mRNA in kidney by a post-transcriptional mechanism.