Nucleotide sequence and estrogen induction of Xenopus laevis 3-hydroxy-3-methylglutaryl-coenzyme A reductase

We have isolated and sequenced overlapping cDNA clones encompassing the entire protein coding region of Xenopus laevis 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase). This 3-kilobase cDNA codes for an 883-amino acid protein, which exhibits extensive amino acid sequence homology to mammalian HMG-CoA reductases. The highly conserved 341-amino acid membrane spanning domain exhibits 89% amino acid sequence identity with hamster HMG-CoA reductase. In contrast to the high degree of homology in the coding regions of the mRNAs, the nucleotide sequences of the 5'- and 3'-untranslated regions of Xenopus and mammalian HMG-CoA reductase mRNAs exhibit negligible homology. Primer extension data suggests that Xenopus HMG-CoA reductase mRNA is transcribed from multiple initiation sites. The Xenopus HMG-CoA reductase cDNA clones were used as hybridization probes to examine estrogen regulation of hepatic HMG-CoA reductase mRNA levels. Northern blot analysis demonstrates that estradiol-17β induced HMG-CoA reductase mRNA in livers of male X. laevis 10-fold within 24 h. Reductase mRNA levels reach a plateau 23-fold higher than basal levels between 5 and 8 days after initial estrogen administration. In contrast to the vitellogenin and retinol binding protein genes whose transcription is induced by estrogen in Xenopus liver, the runoff transcription rate of HMG-CoA reductase does not increase significantly on administration of estradiol-17β. These data suggest that the estrogen induction of HMG-CoA reductase mRNA may be achieved through posttranscriptional mechanisms.