Expression patterns of ERα66 and its novel variant isoform ERα36 in lactotroph pituitary adenomas and associations with clinicopathological characteristics

Treatment Strategies for Dopamine Agonist-Resistant and Aggressive Prolactinomas: A Comprehensive Analysis of the Literature

“…The median scores of ERα66 and ERα36 expression were 6 and 8 in normal pituitaries and 0 and 4 in tumors, respectively. Low expression of ERα36 was associated with higher Ki67 indices and more prominent tumor invasion [21]. Low ERα66 expression was also associated with tumor invasion, increased tumor volumes and dopamine-agonist resistance.…”

“…The major regulators of lactotroph functions are estradiol and dopamine (DA) which interact in controlling cell proliferation and prolactin secretion [20]. In prolactinomas, the main related transcription factors are estrogen receptor-α (ERα) and pituitary transcription factor 1 (PIT1) [21]. Estradiol exerts its cellular functions via specific nuclear receptors, ERα and ERβ, via genomic and nongenomic pathways [21].…”

“…In prolactinomas, the main related transcription factors are estrogen receptor-α (ERα) and pituitary transcription factor 1 (PIT1) [21]. Estradiol exerts its cellular functions via specific nuclear receptors, ERα and ERβ, via genomic and nongenomic pathways [21]. ERα66 is the most commonly encountered type of Erα and a variant of ERα, known as ERα36, is formed from the promoter residing within the first intron of ERα66.…”

“…ERα66 is the most commonly encountered type of Erα and a variant of ERα, known as ERα36, is formed from the promoter residing within the first intron of ERα66. Unlike ERα66, ERα36 does not harbor AF1 and AF2 transcriptional activation domains for binding to estradiol and coactivators [21]. Dimerization and DNA-binding domains and a certain part of the ligand-binding domain still exists in ERα36.…”

“…Dimerization and DNA-binding domains and a certain part of the ligand-binding domain still exists in ERα36. In opposite to ERα66, ERα36 mainly localizes in both the cytoplasm and plasma membrane and exerts nongenomic estrogen signaling [21]. Mahboobifard examined the expression of Ki67, p53, ERα36 and ERα66 by immunohistochemistry in 62 patients with prolactinoma patients and in normal pituitaries [21].…”