The ESC/E(Z) complex, an effector of response to ovarian steroids, manifests an intrinsic difference in cells from women with premenstrual dysphoric disorder.
Level 5 - mechanism / opinion, no new human data
In vitro bench research using human-derived cell lines
PubMed 28044059 · doi:10.1038/mp.2016.229
What was done
Whole-transcriptome RNA sequencing was conducted on lymphoblastoid cell line (LCL) cultures from women with premenstrual dysphoric disorder (PMDD)—who had demonstrated behavioral sensitivity during a hormone suppression and addback trial—and asymptomatic controls. Gene and protein expression across 13 ESC/E(Z) complex genes were measured in steroid-free baseline conditions and following ovarian steroid treatment (estradiol or progesterone). Key transcriptomic findings were assessed for validation in an expanded cohort using qRT-PCR.
What was found
Pathway analysis of untreated LCLs showed that over half of ESC/E(Z) complex genes were overexpressed at the mRNA level in PMDD cells versus controls, with significant upregulation of MTF2, PHF19, and SIRT1 (P < 0.05). In contrast, protein expression of these same genes (including MTF2, PHF19, and SIRT1) was significantly reduced in PMDD cells (P < 0.05). Progesterone increased mRNA expression of several ESC/E(Z) genes in control LCLs but not PMDD LCLs, whereas estradiol decreased expression in PMDD cells. Exact sample sizes, fold changes, and numerical values were not reported in the abstract.
Why it matters
The findings indicate that abnormal behavioral sensitivity to ovarian steroids in PMDD is accompanied by an intrinsic, cell-autonomous dysregulation of gene silencing pathways.
Limits
The abstract does not report the sample sizes for either the discovery RNA-seq cohort or the replication qRT-PCR cohort. The study was conducted in peripheral lymphoblastoid cell lines rather than central nervous system tissue, leaving the direct neural mechanism unmeasured. Quantitative effect sizes, baseline variance, and confidence intervals are omitted from the abstract.
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