ESTROGEN REGULATES THE EXPRESSION OF SEVERAL DIFFERENT ESTROGEN-RECEPTOR MESSENGER-RNA ISOFORMS IN RAT PITUITARY

A 5.2-kb mRNA band that contains estrogen receptor (ER) sequence and e xhibits sex- and tissue-specific expression has been identified in rat pituitary via Northern analysis; this band is composed of at least tw o distinctive ER mRNA isoforms, This mRNA is expressed in high levels in female pituitary but is absent in male pituitary and uterus, wherea s the mRNA encoding the full-length receptor (6.2 kb) is expressed in all the aforementioned tissues. Estradiol treatment potently induces t he expression of the 5.2-kb band in the male pituitary. Oligonucleotid e hybridization and ribonuclease-protection experiments indicate that the pituitary ER variant is missing exons 1-4. Two corresponding cDNA clones, truncated estrogen receptor product 1 and 2 (TERP-1 and TERP-2 ), were isolated by using the anchored PCR Both sequences contain a 31 -bp segment of specific sequence upstream of exon 5; TERP-2, however, contains an additional 66 bp of specific sequence between the 31-bp se gment and exon 5, On Northern analysis, probes complementary to the 31 -bp segment of specific sequence hybridize only to the 5.2-kb band. Im munoblotting identified several proteins in rat pituitary that could r epresent the translation products of these or related transcripts. In summary, several ER isoforms have been identified that exhibit both ti ssue-specific expression and marked estrogen regulation and differ fro m full-length receptor by virtue of sequence upstream of the exon 4/5 boundary, Physiologically, the putative proteins encoded by these or s imilar isoforms might be important modulators of the tissue- and promo ter-specific effects of estradiol.