English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

ΣE3, ΣE4, and ΣE3–4 are naturally occurring estrogen receptor (ER) isoforms, generated through differential splicing of the ERα primary transcript and abundantly expressed in embryonic rat pituitary. Studies in COS cells transfected with full-length ERα or its three splice variants fused to green fluorescent protein (GFP), revealed a different subcellular localization for each isoform. In the absence of estradiol, full-length ERα-GFP was predominantly nuclear, and ΣE3-GFP and ΣE4-GFP were present both in cytoplasm and nucleus, whereas ΣE3–4-GFP was predominantly cytoplasmic. Upon hormone treatment, a dramatic redistribution of full-length ERα-GFP and ΣE3-GFP, from a diffuse to punctate pattern, occurred within the nucleus. In contrast, the distribution of ΣE4-GFP and ΣE3–4-GFP was unaffected. Nuclear fractionation studies showed that full-length ER-α and ΣE3 displayed the same hormone-induced ability to tether to nuclear matrix, whereas nuclear ΣE4 appeared to remain loosely associated to functional nuclear constituents. When cotransfected with an estrogen-inducible reporter plasmid (VIT-TK-CAT) in ER-negative (CHO k1) and ER-positive pituitary (GH4 C1) cells, ΣE3–4 exhibited a very weak estrogen-dependent transactivation activity, whereas ΣE3 had an inhibitory effect on full-length ER action. Conversely, ΣE4 displayed estrogen-independent transcriptional activity in ER-negative cells, and in ER-positive cells, enhanced the estrogen-induced gene expression as efficiently as full-length ERα. In a gel mobility shift assay, phosphorylated ΣE4 was able to form a specific complex with a consensus ERE, while ΣE3 and ΣE3–4 never did bind by themselves. The observed inhibitory action of ΣE3 on estrogen-dependent transcription would rather involve protein-protein interactions such as formation of heterodimers with full-length ERα, as suggested by immunoprecipitation followed by Western blotting. These data suggest that ΣE3 and ΣE4 may play a physiologically relevant role as negative or constitutively positive modulators of transcription, in the developing rat pituitary.

Differential Subcellular Distribution and Transcriptional Activity of ΣE3, ΣE4, and ΣE3–4 Isoforms of the Rat Estrogen Receptor-α