Hyperestrogenicity is a risk factor for endometrial cancer. 17β-estradiol (E2) is known to stimulate both genomic and nongenomic estrogen receptor-α (ERα) actions in a number of reproductive tissues. However, the contributions of transcription-independent ERα signaling on normal and malignant endometrium are not fully understood. Phosphatase and tensin homolog (PTEN) is a tumor suppressor that decreases cellular mitosis primarily through negative regulation of the phosphoinositide 3-kinase/AKT signaling axis. PTEN levels are elevated during the E2 dominated, mitotically active, proliferative phase of the menstrual cycle, indicating possible hormonal regulation of PTEN in the uterus. In order to determine if rapid E2 signaling regulates PTEN, we used ERα positive, PTEN positive, endometrial cells. We show that cytosolic E2/ERα signaling leads to increased phosphorylation of PTEN at key regulatory residues. Importantly, E2 stimulation decreased PTEN lipid phosphatase activity and caused consequent increases in phospho-AKT. We further demonstrate that cytosolic ERα forms a complex with PTEN in an E2-dependent manner, and that ERα constitutively complexes with protein kinase2-α (CK2α), a kinase previously shown to phosphorylate the C-terminal tail of PTEN. These results provide mechanistic support for an E2-dependent, ERα cytosolic signaling complex that negatively regulates PTEN activity through carboxy terminus phosphorylation. Using an animal model, we show that sustained E2 signaling results in increased phospho-PTEN (S380, T382, T383), total PTEN and phospho-AKT (S473). Taken together, we provide a novel mechanism in which transcription-independent E2/ERα signaling may promote a pro-tumorigenic environment in the endometrium.

Purpose of reviewAdnexal torsion remains a diagnostic challenge heavily reliant on high clinical suspicion, with patient presentation and imaging used as adjuncts to aid in its diagnosis. This review summarizes diagnostic and management techniques of adnexal torsion to assist providers when encountering this surgical emergency. Recent findingsCommon findings of adnexal torsion include abdominal pain, nausea, vomiting, and adnexal mass or ovarian enlargement. An elevated neutrophil to lymphocyte ratio may be useful for diagnosis. A 'whirlpool' sign, 'follicular ring' sign, enlarged/edematous ovary, and absent Doppler flow to the ovary are highly suggestive of adnexal torsion. Intraoperative visual diagnosis of ovarian death is highly inaccurate, with only 18--20% of ovaries necrotic on pathological examination. Necrotic appearing ovaries have been shown to have follicular activity on ultrasound one year postoperatively.