Altered estradiol-dependent cellular Ca 2+ homeostasis and endoplasmic reticulum stress response in Premenstrual Dysphoric Disorder.

摘要: Premenstrual Dysphoric Disorder (PMDD) is characterized by debilitating mood symptoms in the luteal phase of menstrual cycle. Prior studies affected women have implicated a differential response to ovarian steroids. However, molecular basis these patients' hormone remains poorly understood. We performed transcriptomic analyses lymphoblastoid cell lines (LCLs) derived from with PMDD and asymptomatic controls cultured under untreated (steroid-free), estradiol-treated (E2), progesterone-treated (P4) conditions. Weighted gene correlation network analysis (WGCNA) transcriptomes identified four modules significant diagnosis x interactions, including one enriched for neuronal functions. Next, gene-level comparing transcriptional across diagnoses, generalized linear model 1522 genes differentially responsive E2 (E2-DRGs). Among top 10 E2-DRGs was physically interacting (NUCB1, DST, GCC2, GOLGB1) involved endoplasmic reticulum (ER)-Golgi function. qRT-PCR validation reproduced interaction (F(1,24)=7.01, p = 0.014) NUCB1, regulator cellular Ca2+ ER stress. Finally, we used thapsigargin (Tg) challenge assay test whether induces differences homeostasis stress PMDD. LCLs had 1.36-fold decrease Tg-induced XBP1 splicing compared controls, 1.62-fold decreased (p 0.005), treatment (F(3,33)=3.51, 0.026) E2-exposed condition. Altered hormone-dependent dynamics may contribute pathophysiology