Estrogen receptor–α messenger RNA variants that lack exon 5 or exon 7 are coexpressed with wild-type form in human endometrium during all phases of the menstrual cycle

Objective We have assessed the expression levels of messenger RNA for estrogen receptor–α and splice variants lacking exon 5 or exon 7 that presumably exert dominant positive (splice variants lacking exon 5) and negative (splice variants lacking exon 7) effects, respectively, on estrogen responses in the human endometrium. Study design This was a prospective study that was conducted at an academic community-based hospital. The patients, aged 18 to 40 years, underwent hysterectomy for benign gynecologic causes. Eighty-one endometrial specimens (46 proliferative, 35 secretory) were analyzed with the use of reverse transcription–polymerase chain reaction assay for the messenger RNA levels of estrogen receptor–α, and splice variants lacking exon 5 and exon 7. Results Wild-type estrogen receptor–α and splice variants splice variants lacking exon 5 and lacking exon 7 messenger RNAs were detected in all endometrial specimens throughout the menstrual cycle. In addition, a double-splice estrogen receptor–α messenger RNA variant (splice variants lacking exon 5 and exon 7) was detected at constant low levels of expression. Semiquantitative analysis showed higher levels of estrogen receptor–α messenger RNA in the early and mid proliferative endometrial phases than in late proliferative and secretory endometrium (P<.05). The splice variant lacking exon 7 messenger RNA expression level was about 10-fold higher than the splice variant lacking exon 5 messenger RNA relative to wild-type estrogen receptor-α messenger RNA (P<.001). The expression of splice variants lacking exon 5 compared with wild-type estrogen receptor–α messenger RNA is relatively constant throughout endometrial development. In contrast, an examination of the ratio of the levels of splice variants lacking exon 7 to wild-type estrogen receptor–α messenger RNA indicated a small, but significantly higher, splice variant lacking exon 7 level in the mid secretory phase (postovulatory days 5-8) than the mid proliferative and early secretory phases (P< .05). Conclusion We found no evidence of differential coexpression of the positive dominant estrogen receptor variant, splice variants lacking exon 5, with wild-type estrogen receptor-α. We did find that the dominant negative splice variant lacking exon 7 was slightly increased relative to wild-type estrogen receptor–α in the postovulatory phase. Future investigation is required to suggest the biologic significance of the observed increased relative expression of the splice variants lacking exon 7 in secretory endometrium and to determine the function of splice variants lacking exon 5 and splice variants lacking exon 7.