The novel 5'-untranslated first exon, exon 0H, of the rat estrogen receptor beta gene.

The multiple untranslated first exons and promoters system has been reported to be involved in the tissue-specific expression of the estrogen receptor alpha (ERalpha) in humans and rats. However, a few reports are available concerning tissue-specific regulation of the expression of the estrogen receptor beta (ERbeta) gene. To investigate the mechanism regulating the expression of the rat ERbeta gene, we analyzed the structure of the 5'-untranslated region (UTR) of the rat testicular ERbeta mRNA using 5'-rapid amplification of the cDNA ends (5'-RACE) method. Sequence analysis revealed the presence of two isoforms of the ERbeta mRNA containing distinct 5'-UTRs. Although the 5'-UTR of one isoform of the messages was identical to the 5'-UTR of the previously reported ERbeta cDNA, the other isoform had a novel sequence in its 5'-UTR. Genomic analysis revealed that the 5'-UTRs of these two mRNA isoforms originated from two distinct untranslated first exons, the previously identified exon termed "exon 0N," and the novel exon we termed "exon 0H," both of which were spliced onto exon 1. We termed these isoforms of the messages containing the exon 0N and exon 0H, the ERbeta mRNA (0N-1) and ERbeta mRNA (0H-1), respectively. Furthermore, the distributions of these mRNA isoforms in several rat tissues were analyzed using the reverse transcription-polymerase chain reaction (RT-PCR) method. The distributions of the two mRNA isoforms differed; the ERbeta mRNA (0N-1) was widely distributed in the tissues examined, while expression of the ERbeta mRNA (0H-1) was restricted to a few tissues such as the anterior pituitary, amygdala, and some peripheral tissues. In conclusion, our findings indicate that the tissue-specific expression of the rat ERbeta gene is regulated, at least in part, by the multiple untranslated first exons system which consists of exon 0N and exon 0H.