The Effect of Low Monotonic Doses of Zearalenone on Selected Reproductive Tissues in Pre-Pubertal Female Dogs--A Review.
The full-length oestrogen receptor (ER) exists in most vertebrates as two separately encoded isoforms. ER splice variants represent truncated or otherwise modified versions of the full-length alpha or beta isoforms of the parent receptor. ERalpha is found on chromosome 6q and encodes a 595 amino acid protein, while ERbeta is found on chromosome 14q and encodes a 530 amino acid protein. These receptors possess differing ligand affinities, are differentially expressed in a tissue-specific fashion and may act antagonistically. Their altered expression has been implicated in the pathophysiology of a diverse range of conditions from cancer progression in hormone-responsive tissues to neurodegenerative disease. Variously co-expressed with full-length ERs, ER splice variants may have a positive or negative influence on transcription either by modifying the effect of the parent receptor or through their own intrinsic activity. To date, the vast majority of studies have used generic primers or antibodies against the full-length receptors and would not distinguish ER-mediated effects associated with various splice variants. Thus the evidence base of the influence of ER splice variants in normal developmental physiology and in the pathogenesis of disease is weak and greater understanding of their role will undoubtedly lead to new therapeutic strategies for disease intervention and treatment. This review aims to compile the current evidence for the presence of ER splice variants in humans, their physiological roles and clinical sequelae.